Methods for Treating Myositis Using FCRN Antagonists - Patent application

Abstract

Provided herein are methods of treating myositis using an effective amount of a human neonatal Fc receptor (FcRn) antagonist. Also provided herein are FcRn antagonists for use in the treatment of myositis, and for use in the manufacture of a medicament for the treatment of myositis.

Description

[Technical field]

[0001] The present disclosure relates to methods of treating myositis, including but not limited to immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), polymyositis (PM), and antisynthetase syndrome (ASyS), which in certain embodiments involve the use of an antagonist of the human neonatal Fc receptor (FcRn), efgartigimod. [Background technology]

[0002] It is estimated that over 2.5% of the human population is affected by autoantibody-driven autoimmune diseases in which autoreactive antibodies are directly pathogenic. Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that include subtypes with various pathologies that primarily target muscle and / or skin as well as other organs. In many subsets, there is a potential role for myositis-specific autoantibodies, most of which are immunoglobulin G (IgG), in disease pathogenesis.

[0003] Many patients with IIM have persistent impairment of muscle function, which leads to difficulties with activities of daily living and reduced health-related quality of life. The typical treatment for IIM is high-dose glucocorticoids combined with immunosuppressants. The deleterious long-term effects of corticosteroids are well established and include osteoporosis, cataracts, and weight gain. No therapy has been approved by the U.S. Food and Drug Administration (FDA) or European regulatory agencies based on the results of randomized controlled trials for IMNM and PM. Only one approved treatment (10% intravenous immunoglobulin [IVIg]) is available for adults with DM, which was approved based on the results of a randomized controlled clinical trial.

[0004] Thus, there is a need in the art for improved IIM treatment options that allow for the tapering or elimination of corticosteroid treatment.

[0005] Therapeutic antagonism of the neonatal Fc receptor (FcRn), a major histocompatibility complex class I-like molecule involved in immunoglobulin G (IgG) recycling and thus responsible for the long half-life of IgG, has been investigated as a strategy to treat IgG-mediated autoimmune diseases such as generalized myasthenia gravis (gMG), immune thrombocytopenia (ITP), and pemphigus (pemphigus vulgaris (PV) and pemphigus foliaceus (PF)). The remarkable clinical efficacy of FcRn antagonism appears to be directly related to the early clearance of pathogenic IgG autoantibodies from the circulation.

[0006] Given their ability to reduce IgG levels, FcRn antagonists may offer a safer and more effective treatment option for patients with IIM. Summary of the Invention

[0007] The present disclosure shows that FcRn antagonists are highly effective in treating myositis. Therefore, the present disclosure is broadly directed to a method for treating myositis with FcRn antagonists.

[0008] In one aspect, provided herein is a method for treating myositis in a subject in need thereof, the method comprising administering to the subject an effective amount of a human neonatal Fc receptor (FcRn) antagonist.

[0009] In some embodiments, the FcRn antagonist comprises two, three, or four FcRn binding regions.

[0010] In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

[0011] In some embodiments, the variant Fc region comprises or consists of two Fc domains that form a homodimer or a heterodimer, hi some embodiments, the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or a heterodimer.

[0012] In some embodiments, the FcRn antagonist comprises an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In some embodiments, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In some embodiments, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0013] In some embodiments, the amino acid sequence of at least one of the Fc domains is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3. In some embodiments, the amino acid sequences of both of the Fc domains are independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3.

[0014] In some embodiments, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In some embodiments, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In some embodiments, the FcRn antagonist is efgaltigimod.

[0015] In some embodiments, the FcRn antagonist is an anti-FcRn antibody, hi some embodiments, the anti-FcRn antibody is selected from the group consisting of rozanolixizumab, nipocalimab, orilanolimab, and batoclimab.

[0016] In some embodiments, the FcRn antagonist is administered to the subject at a fixed dose of about 20 mg to about 20,000 mg, or at a dose of about 0.2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn is administered to the subject at a fixed dose of about 200 mg to about 20,000 mg, or at a dose of about 2 mg / kg to about 200 mg / kg.

[0017] In some embodiments, the FcRn antagonist is administered to the subject at a fixed dose of 20 mg to 20,000 mg, or at a dose of 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn is administered to the subject at a fixed dose of 200 mg to 20,000 mg, or at a dose of 2 mg / kg to 200 mg / kg.

[0018] In some embodiments, the FcRn antagonist is administered subcutaneously once every week, once every two weeks, once every three weeks, once every four weeks, once every month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 20 mg to about 20,000 mg once every week, once every two weeks, once every three weeks, once every four weeks, once every month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 200 mg to about 20,000 mg once every week, once every two weeks, once every three weeks, once every four weeks, once every month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg or about 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of about 1000 mg twice on the same day.

[0019] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 20 mg to 20,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 200 mg to 20,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once every week or once every 2 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1000 mg twice on the same day.

[0020] In some embodiments, the FcRn antagonist is efgartigimod, and efgartigimod is administered subcutaneously once weekly at a fixed dose of about 800 to about 1200 mg. In some embodiments, the FcRn antagonist is efgartigimod, and efgartigimod is administered subcutaneously once weekly at a fixed dose of 800 to 1200 mg. In some embodiments, efgartigimod is administered subcutaneously once weekly at a fixed dose of about 1000 mg. In some embodiments, efgartigimod is administered subcutaneously once weekly at a fixed dose of 1000 mg.

[0021] In some embodiments, the FcRn antagonist is co-formulated with hyaluronidase and administered subcutaneously. In some embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20). In some embodiments, the rHuPH20 is administered at about 11,000 U once a week.

[0022] In some embodiments, the FcRn antagonist is administered intravenously once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 0.2 mg / kg to about 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 2 mg / kg to about 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 3 mg / kg to about 60 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 25 mg / kg once every week or once every two weeks.

[0023] In some embodiments, the FcRn antagonist is administered intravenously at a dose of 0.2 mg / kg to 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 2 mg / kg to 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 3 mg / kg to 60 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 25 mg / kg once every week or once every two weeks.

[0024] In some embodiments, the FcRn antagonist is administered for up to 52 weeks, hi some embodiments, the FcRn antagonist is administered for up to 24 weeks.

[0025] In some embodiments, the FcRn antagonist is administered for at least 24 weeks. In some embodiments, the FcRn antagonist is administered for at least 52 weeks.

[0026] In some embodiments, the method further comprises administering to the subject a dose of a corticosteroid.

[0027] In some embodiments, the dose of the corticosteroid is decreased after 16 weeks of treatment with the FcRn antagonist, hi some embodiments, the dose of the corticosteroid is decreased after 24 weeks of treatment with the FcRn antagonist.

[0028] In some embodiments, the corticosteroid is prednisone. In some embodiments, if the dose of prednisone is administered to the subject at more than 5 mg per day before the dose of prednisone is reduced, the dose of prednisone is reduced after 16 weeks of treatment with FcRn antagonist. In some embodiments, after 16 weeks of treatment with FcRn antagonist, the daily dose of prednisone is reduced by 2.5 mg, and the reduced dose is maintained for 4 weeks. In some embodiments, after 16 weeks of treatment with FcRn antagonist, the daily dose of prednisone is reduced by 2.5 mg every 4 weeks for one or more 4-week periods. In some embodiments, prednisone is administered at 20 mg or less per day.

[0029] In some embodiments, if the prednisone dose is administered to the subject at more than 7.5 mg per day before the prednisone dose is reduced, the prednisone dose is reduced after 24 weeks of treatment with an FcRn antagonist.In some embodiments, after 24 weeks of treatment with an FcRn antagonist, the prednisone daily dose is reduced by 2.5 mg, and the reduced dose is maintained for 4 weeks.In some embodiments, after 24 weeks of treatment with an FcRn antagonist, the prednisone daily dose is reduced by 2.5 mg every 4 weeks for one or more 4-week periods.

[0030] In some embodiments, the myositis is selected from the group consisting of immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), juvenile dermatomyositis (JDM), polymyositis (PM), and antisynthetase syndrome (ASyS).

[0031] In some embodiments, the subject is diagnosed with idiopathic inflammatory myopathy (IIM). In some embodiments, the IIM is selected from the group consisting of IMNM, DM, JDM, PM, and ASyS.

[0032] In some embodiments, the myositis is IMNM.

[0033] In some embodiments, the subject has anti-signal recognition particle (SRP) autoantibodies. In some embodiments, the subject exhibits a reduction in serum anti-SRP autoantibody levels after administration of an anti-FcRn antagonist. In some embodiments, the reduction in serum anti-SRP autoantibody levels after administration of an anti-FcRn antagonist is at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the subject's serum anti-SRP autoantibody levels before administration of an anti-FcRn antagonist. In some embodiments, anti-SRP autoantibodies are undetectable in the subject's serum after administration of an FcRn antagonist.

[0034] In some embodiments, the subject has anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) autoantibodies. In some embodiments, the subject shows a reduction in serum anti-HMGCR autoantibody levels after administration of an anti-FcRn antagonist. In some embodiments, the reduction in serum anti-HMGCR autoantibody levels after administration of an anti-FcRn antagonist is at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the subject's serum anti-SRP autoantibody levels before administration of an anti-FcRn antagonist. In some embodiments, anti-HMGCR autoantibodies are undetectable in the subject's serum after administration of an FcRn antagonist.

[0035] In some embodiments, the myositis is DM or JDM. In some embodiments, the subject has an active DM skin rash. In some embodiments, the active DM skin rash is selected from the group consisting of Gottron papules, Gottron signs, and heliotrope rash.

[0036] In some embodiments, the myositis is PM or ASyS. In some embodiments, the subject has detectable serum levels of myositis-associated antibodies (MAA) or myositis-specific antibodies (MSA). In some embodiments, the MSA is an anti-aminoacyl-tRNA synthetase antibody. In some embodiments, the anti-aminoacyl-tRNA synthetase antibody is selected from the group consisting of anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ antibodies. In some embodiments, the MSA is selected from the group consisting of anti-SRP, anti-HMGCR, anti-Mi-2, anti-TIF1, anti-SAE, anti-NXP, and anti-MDA5 antibodies. In some embodiments, the MAA is selected from the group consisting of anti-PM / Scl75, anti-Ku, anti-snRNP, anti-Ro52 (SSA), anti-Ro / 60 (SSA), and anti-La (SSB) antibodies. In some embodiments, the reduction in serum levels of MAA or MSA after administration of the anti-FcRn antagonist is at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the subject's serum levels of MAA or MSA before administration of the anti-FcRn antagonist. In some embodiments, the serum levels of MAA or MSA are undetectable after administration of the FcRn antagonist.

[0037] In some embodiments, the subject shows at least a 20 point improvement in the TIS. In some embodiments, the subject shows at least a minimal improvement in the TIS within 12 weeks. In some embodiments, the subject shows at least a 20 point improvement in the TIS within 6 weeks.

[0038] In some embodiments, the subject shows at least a 40 point improvement in the TIS.

[0039] In some embodiments, the subject exhibits at least a 60 point improvement in the TIS.

[0040] In some embodiments, the subject shows at least a 20% improvement in MMT8 score. In some embodiments, the subject shows at least a 30% improvement in MMT8 score.

[0041] In some embodiments, the subject exhibits at least a 20% reduction in Patient Global Assessment (PGA) of disease activity. In some embodiments, the subject exhibits at least a 30% reduction in PGA.

[0042] In some embodiments, the method further comprises measuring at least one muscle-related enzyme in the subject, and a reduction in the at least one muscle-related enzyme in the subject indicates an improvement in the disease. In some embodiments, the at least one muscle-related enzyme is selected from the group consisting of creatine kinase, alanine aminotransferase, aspartate aminotransaminase, lactate dehydrogenase, and aldolase. In some embodiments, the at least one muscle-related enzyme is creatine kinase.

[0043] In one aspect, there is also provided an FcRn antagonist for use in the treatment of myositis, wherein the treatment is carried out according to any of the methods described herein.

[0044] In one aspect, there is also provided an FcRn antagonist for use in the manufacture of a medicament for the treatment of myositis, wherein treatment is carried out according to any of the methods described herein.

[0045] In one aspect, provided herein is a method for monitoring the effectiveness of a treatment of myositis in a subject following treatment with a first FcRn antagonist, the method comprising: a) measuring in vitro a serum level of a myositis-associated antibody (MAA) or a myositis-specific antibody (MSA) in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the treatment is ineffective; and if the serum level of MAA or MSA is less than the reference value, the treatment is effective.

[0046] In one aspect, provided herein is a method of treating myositis in a subject receiving a first FcRn antagonist and a corticosteroid dosing regimen, the method comprising: a) administering to the subject an effective amount of a second FcRn antagonist; b) measuring in vitro a serum level of MAA or MSA in a blood sample taken from the subject; and c) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the corticosteroid dosing regimen is maintained, or if the serum level of MAA or MSA is less than the reference value, the corticosteroid dosing regimen is tapered.

[0047] In one aspect, provided herein is a method for treating myositis in a subject, the method comprising: (a) administering to the subject one or more initial doses of an effective amount of a first FcRn antagonist; and (b) if the serum level of MAA or MSA in the subject after step (a) is equal to or greater than a reference value associated with myositis in the subject, administering to the subject one or more further doses of an effective amount of a second FcRn antagonist, or if the serum level of MAA or MSA in the subject after step (a) is less than a reference value associated with active disease in the subject, discontinuing treatment with the first FcRn antagonist.

[0048] In one aspect, provided herein is a method for treating myositis in a subject, the method comprising administering to the subject an effective amount of a second FcRn antagonist, wherein the myositis has recurred in the subject after prior therapy with a first FcRn antagonist, and the subject has a serum level of MAA or MSA that is equal to or greater than a reference value associated with myositis in the subject.

[0049] In one aspect, provided herein is a method for determining whether a subject previously treated for myositis using a first FcRn antagonist requires further treatment with a second FcRn antagonist, the method comprising: a) measuring in vitro the serum level of MAA or MSA in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the subject requires further treatment with the second FcRn antagonist.

[0050] In some embodiments, the subject has been previously treated with a first FcRn antagonist at a fixed dose of about 200 mg to about 20,000 mg, or at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the subject has been previously treated with a first FcRn antagonist at a fixed dose of 200 mg to 20,000 mg, or at a dose of 2 mg / kg to 200 mg / kg.

[0051] In some embodiments, the subject has previously been treated with a first FcRn antagonist at a dose of about 750 mg to about 3000 mg administered subcutaneously.

[0052] In some embodiments, the subject has been previously treated with a first FcRn antagonist at a dose of between 750 mg and 3000 mg administered subcutaneously.

[0053] In some embodiments, the subject has previously been treated with a first FcRn antagonist at a dose of about 3 mg / kg to about 60 mg / kg administered intravenously.

[0054] In some embodiments, the subject has previously been treated with a first FcRn antagonist at a dose of 3 mg / kg to 60 mg / kg administered intravenously.

[0055] In some embodiments, the subject has previously been treated with a first FcRn antagonist at a dose of about 10 mg / kg to about 30 mg / kg administered intravenously.

[0056] In some embodiments, the subject has previously been treated with a first FcRn antagonist at a dose of 10 mg / kg to 30 mg / kg administered intravenously.

[0057] In some embodiments, the effective amount of the second FcRn antagonist is a higher dose than the previous treatment with the first FcRn antagonist.

[0058] In some embodiments, the effective amount of the second FcRn antagonist is a lower dose than the previous treatment with the first FcRn antagonist.

[0059] In some embodiments, an effective amount of the second FcRn antagonist is administered at a fixed dose of about 200 mg to about 20,000 mg, or at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, an effective amount of the second FcRn antagonist is administered at a fixed dose of 200 mg to 20,000 mg, or at a dose of 2 mg / kg to 200 mg / kg.

[0060] In some embodiments, the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 750 mg to about 3000 mg once every week, once every two weeks, once every three weeks, once every four weeks, or once every six weeks.

[0061] In some embodiments, the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0062] In some embodiments, the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg or about 2000 mg once every week, every 2 weeks, every 3 weeks, every 4 weeks, or every 6 weeks.

[0063] In some embodiments, the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0064] In some embodiments, the first FcRn antagonist and the second FcRn antagonist are each the same FcRn antagonist. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region comprises or consists of two Fc domains that form a homodimer or heterodimer. In some embodiments, the FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In some embodiments, the FcRn antagonist is efgaltigimod.

[0065] In some embodiments, the first FcRn antagonist and the second FcRn antagonist are different FcRn antagonists. In some embodiments, the first FcRn antagonist or the second FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region comprises or consists of two Fc domains that form a homodimer or heterodimer. In some embodiments, the first FcRn antagonist or the second FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In some embodiments, the first FcRn antagonist or the second FcRn antagonist is efgaltigimod.

[0066] In some embodiments, the amino acid sequence of at least one of the Fc domains is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3. In some embodiments, the amino acid sequences of both of the Fc domains are independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3.

[0067] In some embodiments, the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist is efgartigimod.

[0068] In some embodiments, the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3.

[0069] In some embodiments, the anti-FcRn antibody is rozanolixizumab, nipocalimab, orilanolimab, or batoclimab.

[0070] In some embodiments, the patient has not been previously treated with efgartigimod.

[0071] In some embodiments, the subject has one or more physical symptoms of myositis after treatment with the first FcRn antagonist.

[0072] In some embodiments, the subject has a serum level of MAA or MSA associated with myositis flare. In some embodiments, the MSA is selected from the group consisting of anti-SRP, anti-HMGCR, anti-Mi-2, anti-TIF1, anti-SAE, anti-NXP, anti-MDA5, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ. In some embodiments, the MAA is selected from the group consisting of anti-PM / Scl75, anti-Ku, anti-snRNP, anti-Ro52 (SSA), anti-Ro / 60 (SSA), and anti-La (SSB).

[0073] In some embodiments, the myositis is selected from the group consisting of IMNM, DM, JDM, PM, and ASyS. [Brief description of the drawings]

[0074] [Figure 1] Schematic diagram of prophylactic efgartigimod treatment protocol in a mouse model of immune-mediated necrotizing myopathy (IMNM). Groups of n=8 complement C5-deficient C57BL / 10 Snj C5def (C5- / -) mice received daily intraperitoneal injections of IgG-depleted human serum as a source of human complement. To prevent xenoimmunization against human proteins, C5- / - mice were pretreated with a single injection of cyclophosphamide (day -1). Disease was induced by injection of 2 mg of IgG purified from an anti-HMGCR autoAb+ IMNM patient or a healthy donor as a control (days 0 and 4). C5- / - mice were treated in a prophylactic setting with subcutaneous injections of 20 mg / kg efgartigimod (days -1, 2, 4 and 6).

[0075] [Diagram 2] FIG. 1 is a set of graphs showing human IgG and anti-HMGCR titers. Human IgG titers were determined by ELISA (left panel) and anti-HMGCR+ autoantibody (aAb) titers were determined by ALBIA (right panel) in serum of C57BL / 10 Snj C5def (C5- / -) mice receiving control IgG or anti-HMGCR+ IgG with or without efgartigimod. Levels of total IgG or anti-HMGCR IgG aAb were monitored in mouse serum by ELISA and ALBIA, respectively. Data are presented as mean ± SD; ***p<0.005 by Mann-Whitney two-tailed test. Experiments were performed in triplicate (Exp1-3).

[0076] [Diagram 3] FIG. 1 is a set of graphs showing grip strength (left panels) and muscle strength (right panels) in C57BL / 10 Snj C5def (C5- / -) mice following injection of control IgG or anti-HMGCR+ IgG with or without efgartigimod. Muscle strength was assessed by measurement of gastrocnemius muscle strength upon electrical stimulation of the sciatic nerve (anesthetized animals). Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test. Experiments were performed in triplicate (Exp1-3).

[0077] [Figure 4A] A set of four images showing the degree of staining of human IgG (with anti-human IgG) in mouse muscle tissue. Top left: negative control (mouse not treated with human IgG); Top right: mouse treated with total IgG from a healthy donor; Bottom left: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies; Bottom right: mouse treated with efgaltigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies. [Figure 4B]A set of four images showing the degree of nuclear (with DAPI) and human IgG (with anti-human IgG) staining in mouse muscle tissue. Top left: negative control (mouse not treated with human IgG); Top right: mouse treated with total IgG from a healthy donor; Bottom left: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies; Bottom right: mouse treated with efgaltigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies.

[0078] [Figure 5A] Set of three images showing hematoxylin and eosin (H&E) staining of frozen sections of mouse muscle tissue showing necrotic myofibers. Left: mouse treated with total IgG from a healthy donor (control IgG); center: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies (anti-HMGCR+ IgG); right: mouse treated with efgaltigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies. Triangles indicate necrotic cells. [Figure 5B] Graph showing quantification of necrotic myofibers in C57BL / 10 Snj C5def (C5- / -) mice after injection of control IgG or anti-HMGCR+ IgG with or without efgartigimod. Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test. [Figure 5C] Graph showing quantification of muscle fiber regeneration in C57BL / 10 Snj C5def (C5- / -) mice after injection of control IgG or anti-HMGCR+ IgG with or without efgartigimod. Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test.

[0079] [Figure 6A]A set of schematic diagrams of the efgaltigimod therapeutic treatment protocol in a mouse model of immune-mediated necrotizing myopathy (IMNM). Groups of n=8 Rag2-deficient (Rag2- / -) C57 / BL6 mice received daily intraperitoneal injections of IgG-depleted human serum as a source of human complement. The rationale for using Rag2- / - mice was to prevent xenoimmunization against human proteins. Disease was induced by injection of 2 mg of IgG purified from anti-HMGCR auto-Ab+ IMNM patients or healthy donors as controls (days 0, 4 ± 8, 12, 16). Rag2- / - mice were treated in a therapeutic setting (days 8, 11, 15) after disease induction by anti-HMGCR auto-Ab+ IgG injection. [Figure 6B] A set of schematic diagrams of the efgaltigimod therapeutic treatment protocol in a mouse model of immune-mediated necrotizing myopathy (IMNM). Groups of n=8 Rag2-deficient (Rag2- / -) C57 / BL6 mice received daily intraperitoneal injections of IgG-depleted human serum as a source of human complement. The rationale for using Rag2- / - mice was to prevent xenoimmunization against human proteins. Disease was induced by injection of 2 mg of IgG purified from anti-HMGCR auto-Ab+ IMNM patients or healthy donors as controls (days 0, 4 ± 8, 12, 16). Rag2- / - mice were treated in a therapeutic setting (days 8, 11, 15) after disease induction by anti-HMGCR auto-Ab+ IgG injection.

[0080] [Figure 7] Graph showing reduction of human IgG titers in a mouse model of IMNM in response to therapeutic treatment with efgartigimod. Levels of total IgG were monitored in mouse serum by ELISA. Data are presented as mean ± SD; **p<0.01, ***p<0.005 by two-tailed Mann-Whitney test.

[0081] [Figure 8]Graph showing reduction of anti-HMGCR titers in a mouse model of IMNM in response to therapeutic treatment with efgartigimod. Levels of anti-HMGCR IgG aAb were monitored in mouse serum by ALBIA. Data are presented as mean ± SD; **p<0.01, ***p<0.005 by two-tailed Mann-Whitney test.

[0082] [Figure 9] 1 is a graph showing recovery of grip strength in a mouse model of IMNM in response to therapeutic treatment with efgartigimod. Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test.

[0083] [Figure 10] FIG. 1 is a graph showing recovery of muscle strength in a mouse model of IMNM in response to therapeutic treatment with efgartigimod. Data are presented as mean ± SD; *p<0.05 by two-tailed Mann-Whitney test. Muscle strength was assessed by measuring gastrocnemius strength during electrical stimulation of the sciatic nerve (anesthetized animals).

[0084] [Figure 11A] A set of four images showing the degree of staining for human IgG (with anti-human IgG) in muscle tissue of mice in response to therapeutic treatment with efgartigimod. Top left: negative control (mouse not treated with human IgG); Top right: mouse treated with total IgG from a healthy donor; Bottom left: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies; Bottom right: mouse treated with efgartigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies. [Figure 11B]A set of four images showing the degree of nuclear (by DAPI) and human IgG (by anti-human IgG) staining in muscle tissue from mice in response to therapeutic treatment with efgartigimod. Top left: negative control (mouse not treated with human IgG); Top right: mouse treated with total IgG from a healthy donor; Bottom left: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies; Bottom right: mouse treated with efgartigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies.

[0085] [Figure 12] Set of three images showing hematoxylin and eosin (H&E) staining of frozen sections of muscle tissue showing necrotic and regenerating muscle fibers in mice in response to therapeutic treatment with efgartigimod. Left: mouse treated with total IgG from a healthy donor (control IgG); center: mouse treated with total IgG from an IMNM patient positive for anti-HMGCR autoantibodies (anti-HMGCR+ IgG); right: mouse treated with efgartigimod + total IgG from an IMNM patient positive for anti-HMGCR autoantibodies. Triangles indicate necrotic cells and stars indicate regenerating cells.

[0086] [Figure 13] FIG. 13 is a graph showing quantification of necrotic muscle fibers in Rag2- / - C57 / BL6 mice following injection of control IgG or anti-HMGCR+ IgG with or without efgartigimod. Muscle biopsies were taken on day 18. Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test.

[0087] [Figure 14] FIG. 13 shows quantification of regenerating muscle fibers in Rag2-deficient (Rag2- / -) C57 / BL6 mice following injection of control IgG or anti-HMGCR+ IgG with or without efgartigimod. Muscle biopsies were taken on day 18. Data are presented as mean ± SD; *p<0.05, **p<0.01 by two-tailed Mann-Whitney test. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0088] The present disclosure provides engineered FcRn antagonists and methods for their use in the treatment of myositis, including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), polymyositis (PM), and antisynthetase syndrome (ASyS). Advantageously, the methods disclosed herein allow for rapid treatment of disease and the possibility of tapering or even ceasing corticosteroids after achieving clinical remission. The present disclosure shows that FcRn antagonists are highly effective in treating myositis. Treatment with FcRn antagonists significantly reduced myositis-specific autoantibodies and improved muscle strength within 9 days in an animal model of immune-mediated necrotizing myopathy (IMNM), an idiopathic inflammatory myopathy.

[0089] definition As used herein, the term "FcRn" refers to neonatal Fc receptor. Exemplary FcRn molecules include human FcRn, which is encoded by the FCGRT gene as shown in RefSeq NM 004107. The amino acid sequence of the corresponding protein is shown in RefSeq NP_004098.

[0090] As used herein, the term "FcRn antagonist" refers to any agent that specifically binds to FcRn and inhibits the binding of an immunoglobulin to FcRn (e.g., human FcRn). In one embodiment, the FcRn antagonist is an Fc region (e.g., a variant Fc region disclosed herein) that specifically binds to FcRn via the Fc region and inhibits the binding of an immunoglobulin to FcRn. In one embodiment, the FcRn antagonist is not a full-length IgG antibody. In one embodiment, the FcRn antagonist comprises an antigen-binding site that binds to a target antigen and a variant Fc region. In one embodiment, the FcRn antagonist is an Fc fragment that comprises or consists of an Fc region and lacks an antigen-binding site. In one embodiment, the term "FcRn antagonist" refers to an antibody or antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain or its Fc region and inhibits the binding of an Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn.

[0091] As used herein, the terms "antibody" and "antibodies" include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules containing an antibody CDR, VH region, or VL region. Exemplary antibodies include monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-antibody heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (sdAbs), monovalent antibodies, single chain antibodies or single chain Fvs (scFvs), camelized antibodies, affibody molecules, humanized antibodies, VHH fragments, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFvs), anti-idiotypic (anti-Id) antibodies (including, for example, anti-anti-Id antibodies), and antigen-binding fragments of any of the above. An antibody can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclass (e.g., IgG 2a or IgG 2b )

[0092] As used herein, the term "Fc domain" refers to a portion of a single immunoglobulin heavy chain that includes both the CH2 and CH3 domains of an antibody. In some embodiments, the Fc domain includes at least a portion of the hinge (e.g., upper, middle, and / or lower hinge region), the CH2 domain, and the CH3 domain. In some embodiments, the Fc domain does not include the hinge region.

[0093] As used herein, the term "hinge region" refers to the portion of a heavy chain molecule that connects the CH1 domain to the CH2 domain. This hinge region comprises approximately 25 amino acid residues and is flexible, thus allowing the two N-terminal antigen-binding regions to move independently. The hinge region can be subdivided into three different domains: the upper, middle, and lower hinge domains. The FcRn antagonists of the present disclosure can include all or any portion of the hinge region. In some embodiments, the hinge region is from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence of EPKSCDKTHTCPPCP (SEQ ID NO: 12).

[0094] As used herein, the term "Fc region" refers to the portion of an immunoglobulin formed by the Fc domains of its two heavy chains. The Fc region may be a wild-type Fc region (native Fc region) or a variant Fc region. A native Fc region is a homodimer. The Fc region may be derived from any naturally occurring immunoglobulin. In some embodiments, it is formed from an IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed from an IgG heavy chain constant region. In some embodiments, the IgG heavy chain is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region. In some embodiments, the Fc region is formed from an IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region comprises a G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype. See, e.g., Jefferis and Lefranc (2009) mAbs 1(4):332-338, and de Taeye et al. (2020) Front Immunol. 11:740, which are incorporated by reference in their entireties.

[0095] As used herein, the term "variant Fc region" refers to an Fc region having one or more modifications relative to a native Fc region. Modifications can include amino acid substitutions, additions and / or deletions, linking of additional moieties, and / or modification of native glycans. The term encompasses heterodimeric Fc regions in which each of the constituent Fc domains is different. The term also encompasses single chain Fc regions in which the constituent Fc domains are linked together by linker moieties.

[0096] As used herein, the term "FcRn-binding fragment" refers to a portion of an Fc region sufficient to confer FcRn binding.

[0097] As used herein, the term "EU position" refers to an amino acid position in the EU numbering convention for the Fc region as described in Edelman, GM et al., Proc. Natl. Acad. USA, 63, 78-85 (1969), and Rabat et al, "Sequences of Proteins of Immunological Interest," USDept. Health and Human Services, 5th edition, 1991.

[0098] As used herein, the term "baseline" refers to measurements in a patient, e.g., the patient's blood or urine (e.g., B cell frequency, IgG levels), prior to the first administration (e.g., intravenous or subcutaneous administration) of a therapy (e.g., an FcRn antagonist).

[0099] As used herein, the term "autoantibody-mediated disease" refers to any disease or disorder in which the underlying pathology is caused, at least in part, by pathogenic IgG autoantibodies.

[0100] As used herein, the terms "treat", "treating" and "treatment" refer to therapeutic or prophylactic measures as described herein. A "treatment" method employs administration of a polypeptide to a subject having or susceptible to a disease or disorder to prevent, cure, delay, reduce the severity of, or ameliorate a disease or disorder, or one or more symptoms of a recurrent disease or disorder, or to extend the subject's survival beyond that expected in the absence of such treatment.

[0101] As used herein, in the context of administering a therapy, the term "effective amount" refers to the amount of the therapy that achieves a desired prophylactic or therapeutic effect.

[0102] As used herein, the term "dose" or "dosage" refers to the amount of a drug administered to a subject in a single administration.

[0103] As used herein, the terms "fixed dose" or "flat dose" both refer to a dose that does not vary based on subject characteristics (e.g., weight, e.g., within a set range; sex; age, e.g., within a set range, etc.).

[0104] As used herein, the term "prednisone equivalent" refers to a dose of prednisone or an equivalent amount of a systemic corticosteroid other than prednisone. Systemic corticosteroids are well known and include compounds of various potencies and formulations. They are usually formulated as injections or pills. Examples of commercially available systemic corticosteroids include, but are not limited to, betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, prednisolone, and triamcinolone.

[0105] As used herein, the term "remission" refers to a patient who has no new markers of autoantibody-mediated disease and has completely resolved or been cured of baseline markers of disease.

[0106] As used herein, the term "relapse" or "flare" refers to a patient having an autoantibody-mediated disease having the appearance of physical symptoms and / or an increase in markers of the autoantibody-mediated disease after a period of remission of the autoantibody-mediated disease.

[0107] As used herein, the term "subject" or "patient" or "participant" includes any human or non-human animal. In one embodiment, the subject, patient, or participant is a human or non-human mammal. In one embodiment, the subject, patient, or participant is a human.

[0108] As used herein, the terms "about" or "approximately," when referring to a measurable value, such as a dosage, encompass variations of ±20%, ±15%, ±10%, ±5%, ±1%, or ±0.1% of a given value or range, as appropriate for practicing the methods disclosed herein.

[0109] Myositis Myositis is a group of inflammatory disorders of skeletal muscle, also called idiopathic inflammatory myopathy (IIM). This heterogeneous group of diseases includes many subtypes with various pathologies. There is evidence that some IIM subtypes, especially those involving certain subtypes of polymyositis (PM), such as immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), and antisynthetase syndrome (ASyS), are likely driven by IgG autoantibodies (including myositis-specific antibodies [MSA] and myositis-associated antibodies [MAA]).

[0110] Common symptoms of chronic IIM include slow but progressive muscle weakness. Inflammation can damage muscle fibers, causing weakness and affecting the arteries and blood vessels that pass through the muscle. Other symptoms include fatigue after walking or standing, frequent episodes of tripping or falling, and difficulty swallowing or breathing. Some individuals may have muscle pain or tender muscles.

[0111] Immune-mediated necrotizing myopathy (IMNM) represents a rare and relatively newly recognized distinct group of inflammatory myopathies. IMNM can occur at any age, but usually affects adults. Symptoms are similar to polymyositis and dermatomyositis, with both upper and lower body weakness and difficulty rising from a low chair, climbing stairs, or lifting objects. However, the onset of these symptoms can be more severe and sudden, peaking over days or weeks. Other symptoms include fatigue, weight loss, and muscle pain. IMNM is characterized by necrosis of skeletal muscle fibers accompanied by high creatine kinase levels and deposition of C5b-9 membrane attack complex (MAC). Most IMNM patients have autoantibodies (aAbs) directed against signal recognition particle (SRP) or hydroxy-3-methylglutaryl-CoaA reductase (HMGCR). In addition to their role as biomarkers, the observed relationship between aAb titers and disease severity provides early indications that these aAbs may be pathogenic and thus may be central players in IMNM pathophysiology.

[0112] Polymyositis (PM) affects skeletal muscles and is rarely seen in children. Onset generally occurs between the ages of 30 and 60. Symptoms vary widely from person to person, which can make diagnosis difficult. Untreated progressive muscle weakness can lead to difficulty swallowing, speaking, rising from a sitting position, climbing stairs, lifting objects, or reaching overhead. Some people with polymyositis may also develop arthritis, shortness of breath, cardiac arrhythmia (irregular heartbeat), or congestive heart failure (when the heart can no longer pump enough oxygen-rich blood). Antisynthetase syndrome (ASyS) is a polymyositis subtype associated with anti-tRNA synthetase autoantibodies (e.g., anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ) and one or more of Raynaud's phenomenon, arthritis, interstitial lung disease, fever not attributable to another cause, or evidence of myositis.

[0113] Dermatomyositis (DM) is characterized by a skin rash that precedes or accompanies progressive muscle weakness. The rash appears patchy and characteristically affects the eyelids and muscles used to extend or straighten joints (such as the knuckles, elbows, knees, and toes). The rash may also occur on the face, neck, shoulders, upper chest, back, and other sites and may be accompanied by swelling in the affected areas. One form the rash takes is called "heliotrope" (light purple) or lilac, but can also be red. This can occur around the eyes along with swelling, but what is called a "shawl" (around the neck) or "V sign" on the upper chest can also occur on the upper chest or back, and may also occur on the face, upper arms, thighs, or hands. Another form the rash can take is called Gottron's sign, which is a red or purple, sometimes scaly, slightly elevated papule that erupts on one of the knuckles (metacarpophalangeal or interphalangeal joints). The rash may occur without obvious muscle involvement and is often more noticeable with exposure to sunlight.

[0114] Adults with dermatomyositis may experience weight loss or low-grade fever, may have inflamed lungs, and may be sensitive to light. Unlike polymyositis, adult dermatomyositis may be associated with tumors in the breast, lungs, female genitals, or intestines. Children and adults with dermatomyositis may develop calcium deposits (calcinosis) under the skin or in the muscles. Raised reddish bumps (Gottron papules) may appear on the knuckles. Calcinosis most often occurs 1 to 3 years after the onset of the disease, but may occur many years later.

[0115] Anti-TIF1 (human transcription intermediary factor) antibodies are the most common autoantibody found in children with juvenile dermatomyositis. It is also found in adults with dermatomyositis, and high levels of the antibody are associated with an increased risk of cancer-associated DM in adults. Other autoantibodies specific for DM include anti-NXP (nuclear matrix protein) antibodies, anti-SAE (anti-small ubiquitin like modifier activating enzyme heterodimer) antibodies, and anti-IFN-induced melanoma differentiation-associated protein 5 (MDA5).

[0116] In some cases of polymyositis and dermatomyositis, distal muscles may become affected as the disease progresses. Polymyositis and dermatomyositis may be associated with collagen vascular diseases or autoimmune diseases such as lupus. Polymyositis may also be associated with infectious disorders such as HIV, which causes AIDS.

[0117] Anti-PM / Scl is associated with pulmonary problems and overlap with polymyositis and scleroderma. Anti-Ro / SSA antibodies (e.g., anti-Ro52 (SSA) and anti-Ro60 (SSA)) are the most common MAAs in myositis and frequently occur together with anti-ARS antibodies or other MAAs (e.g., anti-Ku, anti-snRNP, and anti-La (SSB)).

[0118] Many patients with IIM have persistent impairment of muscle function, which leads to difficulties with activities of daily living and reduced health-related quality of life. The typical treatment for IIM is high-dose glucocorticoids combined with immunosuppressants. The deleterious long-term effects of corticosteroids are well established and include osteoporosis, cataracts, and weight gain. No therapy has been approved by the U.S. Food and Drug Administration (FDA) or European regulatory agencies based on the results of randomized controlled trials for IMNM and PM. Only one approved treatment (10% intravenous immunoglobulin [IVIg]) is available for adults with DM, which was approved based on the results of a randomized controlled clinical trial.

[0119] The Total Improvement Score (TIS) has been approved by the American College of Rheumatology [ACR] and the European League Against Rheumatism [EULAR] to monitor IIM symptoms. This score is a weighted sum of improvements in six Core Set Measures of Disease Activity (CSM): Physician Global Assessment of Disease Activity (MDGA), Patient Global Assessment of Disease Activity (PGA), Manual Muscle Testing-8 (MMT8), Health Assessment Questionnaire Disability Index (HAQ-DI), muscle enzymes, and extramuscular disease activity (assessed by the Myositis Disease Activity Assessment Tool [MDAAT]).

[0120] The TIS includes CSM scored by both the patient and the physician, taking into account muscle symptoms and extramuscular disease activity and physical function. It also includes objective disease activity parameters, i.e., activity of muscle enzymes. The International Myositis Assessment and Clinical Studies Group (IMACS) recommends a minimal TIS as the primary endpoint for IIM treatment studies. Criteria can be used with the TIS as a continuous outcome measure or as a categorical outcome of improvement (minimal, moderate, or great improvement). IMACS considers a minimal TIS threshold to be clinically significant for distinguishing between treatment groups in clinical studies. To date, several phase 3 studies in patients with IIM have used the TIS as a primary endpoint (NCT02728752, NCT03981744, NCT04044690, and NCT04999020).

[0121] The absolute percentage change from baseline in each measurement with various weights is combined to obtain the TIS on a scale of 0 to 100. Higher scores indicate greater improvement. Improvement is defined by the following increase in the TIS:

[0122] Minimal improvement - at least 20 points,

[0123] Moderate improvement - at least 40 points,

[0124] Significant improvement - at least 60 points.

[0125] MDGA

[0126] The MDGA is a tool that measures a physician's global assessment of a participant's overall disease activity, defined as potentially reversible pathology or physiology resulting from IIM. Physicians assess disease activity on the MDGA using a 10 cm VAS. Overall disease activity is assessed by drawing vertical marks on the VAS 10 cm from the left end of the line (no evidence of disease activity), the midpoint of the line (moderate disease activity), and the right end of the line (very active or severe disease activity).

[0127] PGA

[0128] The PGA is a tool that measures a patient's global assessment of overall disease activity at the time of assessment using a 10 cm VAS. Patients rate their overall disease activity by drawing a vertical mark on the 10 cm VAS from the left end of the line (no evidence of disease activity) to the right end of the line (very active or severe disease activity).

[0129] MMT8

[0130] The MMT8 is a physician-administered assessment of strength in a set of eight specified muscles tested bilaterally (proximal muscles [deltoid, biceps, gluteus maximus, gluteus medius, quadriceps], and distal muscles [wrist extensors and ankle dorsiflexors], potential score 0-140) and axially (cervical flexors, potential score 0-10).

[0131] HAQ-DI

[0132] The HAQ-DI is recommended by IMACS as a CSM in treatment studies to assess physical function and report myositis disease activity. Patients rate their usual abilities within the past week in eight categories: dressing and grooming, standing, walking, reaching, eating, hygiene, grasping, and activity. Each category has two to three questions that participants score by using a four-point scale ranging from 0 (no difficulty) to 3 (cannot do). Scores may be adjusted based on the patient's answers to individual questions regarding the need for assistive devices and equipment, or help from others. The questionnaire may include a VAS. Respondents are asked to record how much pain they have had due to their illness in the past week, from 0 (no pain) to 100 (severe pain).

[0133] Muscle Enzymes

[0134] Muscle-related enzymes include creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), and aldolase. These enzymes are measured in patient blood samples using validated methods. A reduction in the prevalence of at least one of these enzymes indicates improvement in myositis.

[0135] MDAAT

[0136] The MDAAT is a composite tool that includes MYOACT, a serial physician assessment of disease activity in various organ systems modified from the Vasculitis Activity Index, and MITAX, modified from the British Isles Lupus Assessment Group approach to assess disease activity in lupus. Among the MYOACT components of the MDAAT assessment, the Extramuscular Global Assessment is a CSM of the TIS and is a tool used by physicians for an overall assessment of disease activity in all extramuscular organ systems. This assessment specifically excludes muscle disease activity. Physicians use a 10 cm VAS to assess the participant's overall disease activity in all extramuscular systems within the past 4 weeks caused by active IIM disease. The MITAX component of the MDAAT assesses disease activity in various organ systems by assessing 26 clinical features within the past 4 weeks caused by active disease, using a 5-point scale: 0 = absent in the past 4 weeks, 1 = improved, 2 = same, 3 = worse, 4 = new.

[0137] CDASI

[0138] The CDASI is a skin-specific outcome measure used to assess disease in patients with DM. Disease in 15 different anatomical locations is assessed using three activity measures (erythema, scaling, erosion / ulceration) and two damage measures (poikiloderma, calcification). The three activity measures in 15 anatomical locations can add up to 90 points. The hands, periungual Gottron papules, and alopecia can add up to 10 points. The two damage measures in 15 anatomical locations can add up to 30 points for the Gottron hands and an additional 2 points for the alopecia. The CDASI also assesses the presence and severity of Gottron papules, periungual changes, and alopecia. The resulting activity and damage scores range from 0 to 100 and 0 to 32, respectively. Higher scores indicate greater disease severity.

[0139] FcRn antagonists FcRn antagonists useful in the methods and uses provided herein include any molecule that binds to and inhibits FcRn, including, but not limited to, any anti-FcRn antibody, any anti-FcRn binding region, or any Fc domain or Fc region.

[0140] In some embodiments, the FcRn antagonist disclosed herein comprises two, three, or four FcRn binding regions, such as Fc regions.

[0141] Any Fc region can be modified to generate a variant Fc region for use in the methods disclosed herein. Generally, the Fc region, or an FcRn-binding fragment thereof, is derived from a human immunoglobulin. However, it is understood that the Fc region can be derived from an immunoglobulin of any other mammalian species, including, for example, camelid species, rodents (e.g., mouse, rat, rabbit, guinea pig), or non-human primate (e.g., chimpanzee, macaque) species. Furthermore, the Fc region or a portion thereof can be derived from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, and any immunoglobulin isotype, including IgG1, IgG2, IgG3, and IgG4. In one embodiment, the Fc region is an IgG Fc region (e.g., a human IgG region). In one embodiment, the Fc region is an IgG1 Fc region (e.g., a human IgG1 region). In one embodiment, the Fc region is a chimeric Fc region that includes portions of several different Fc regions. Suitable examples of chimeric Fc regions are described in US2011 / 0243966A1, which is incorporated herein by reference in its entirety. Various Fc region gene sequences (e.g., human constant region gene sequences) are available in the form of public deposits.

[0142] The Fc region can be further truncated or internally deleted to generate its minimal FcRn-binding fragment. The ability of the Fc region fragment to bind to FcRn can be determined using any art-recognized binding assay, such as ELISA.

[0143] To improve the manufacturability of the FcRn antagonists disclosed herein, the Fc region preferably does not contain any non-disulfide bonded cysteine ​​residues. Thus, in one embodiment, the Fc region does not contain any free cysteine ​​residues.

[0144] Any Fc variant, or FcRn-binding fragment thereof, that specifically binds to FcRn with increased affinity and reduced pH-dependence relative to the native (i.e., wild-type) Fc region can be used in the methods disclosed herein. In one embodiment, the variant Fc region comprises amino acid changes, substitutions, insertions, and / or deletions that confer the desired characteristics. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, or an FcRn-binding fragment thereof, that binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region, or an FcRn-binding fragment thereof, that binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises a variant Fc region, or an FcRn-binding fragment thereof, that binds to FcRn with higher affinity at both acidic and neutral pH.

[0145] In some embodiments, the variant Fc region is derived from the Fc region of any native immunoglobulin. In some embodiments, the native immunoglobulin is a human immunoglobulin. In some embodiments, the immunoglobulin is IgA, IgD, IgE, or IgG. In some embodiments, the immunoglobulin is IgG. In some embodiments, the immunoglobulin is human IgA, human IgD, human IgE, or human IgG. In some embodiments, the immunoglobulin is human IgG. In some embodiments, the IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region is altered from a human IgG1 Fc region. In some embodiments, the human IgG1 Fc region comprises a G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype.

[0146] In one embodiment, the variant Fc region, or FcRn-binding fragment thereof, consists of two Fc domains. In one embodiment, the FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0147] In one embodiment, the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or a heterodimer. In one embodiment, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0148] In one embodiment, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3. In one embodiment, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3.

[0149] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 3. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 3.

[0150] In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region comprises two Fc domains, the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.

[0151] In certain embodiments, the variant Fc region is a heterodimer, and the constituent Fc domains are different from each other. Methods for generating Fc heterodimers are known in the art (see, for example, US 8,216,805, which is incorporated herein by reference in its entirety). In one embodiment, the FcRn antagonist consists of a variant Fc region, the variant Fc region consists of two Fc domains that form a heterodimer, and the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, which consists of or comprises two Fc domains forming a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, which consists of or comprises two Fc domains forming a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0152] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:1.

[0153] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:2.

[0154] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:3.

[0155] In one embodiment, the FcRn antagonist is efgartigimod (CAS Registry Number 1821402-21-4). As used herein, the term "efgartigimod" is interchangeable with "efgartigimod-alpha". In some embodiments, efgartigimod is efgartigimod-alpha fcab. [Table 1]

[0156] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161).

[0157] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is nipocalimab, also known as M281. Nipocalimab is a full-length "Fc-dead" IgG1 monoclonal antibody. Nipocalimab has been administered as an intravenous infusion in a Phase 2 clinical trial for the treatment of myasthenia gravis (MG), warm autoimmune hemolytic anemia (WAIHA), and hemolytic disease of the fetus and newborn (HDFN). Nipocalimab comprises the light chain (SEQ ID NO: 4) and heavy chain (SEQ ID NO: 5) sequences shown in Table 2 below. [Table 2]

[0158] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is rozanolixizumab, also known as UCB7665. Rozanolixizumab is a full-length humanized IgG4 monoclonal antibody. Rozanolixizumab has been administered as a subcutaneous infusion in ongoing clinical trials for MG, immune thrombocytopenia (FTP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Rozanolixizumab comprises the light chain (SEQ ID NO: 6) and heavy chain (SEQ ID NO: 7) sequences shown in Table 3 below. [Table 3]

[0159] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is orilanolimab, also known as SYNT001. Orilanolimab is another full-length humanized IgG4 monoclonal antibody. Orilanolimab has been administered as an intravenous infusion in a Phase 2 clinical trial for the treatment of WAIHA. Orilanolimab comprises the light chain (SEQ ID NO: 8) and heavy chain (SEQ ID NO: 9) sequences shown in Table 4 below. [Table 4]

[0160] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is batoclimab, also known as IMVT1401 / RVT1401 / HBM9161. Batoclimab is another full-length "Fc-dead" IgG1 monoclonal antibody. Batoclimab is administered as a subcutaneous injection in ongoing Phase 2 clinical trials for the treatment of MG and Graves' ophthalmopathy. Batoclimab comprises the light chain (SEQ ID NO: 10) and heavy chain (SEQ ID NO: 11) sequences shown in Table 5 below. [Table 5]

[0161] Pharmaceutical Compositions In one aspect, the present disclosure provides pharmaceutical compositions comprising FcRn antagonists for use in methods of treating myositis. In certain embodiments, these compositions comprise or consist of a variant Fc region, or an FcRn-binding fragment thereof, that specifically binds to FcRn, particularly human FcRn, with increased affinity and reduced pH-dependence compared to native Fc regions. In other embodiments, the FcRn antagonist composition is an antibody or an antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain and inhibits the binding of the Fc region of an immunoglobulin to FcRn. In general, these FcRn antagonists inhibit the binding of Fc-containing agents (e.g., antibodies and immunoadhesins) to FcRn in vivo, thereby increasing the rate of degradation of the Fc-containing agents and concomitantly reducing the serum levels of these agents.

[0162] In one embodiment, the FcRn antagonist is efgartigimod. Efgartigimod (ARGX-113) is a modified human immunoglobulin (Ig) gamma (IgG) 1-derived Fc of the za allotype that binds to human FcRn with nanomolar affinity. Efgartigimod encompasses the IgG1 Fc region (comprising residues of SEQ ID NO:2) and has been engineered using ABDEG™ technology to increase its affinity for FcRn at both physiological and acidic pH. Vaccaro C et al., Nat Biotechnol. 2005;23(10):1283. See also U.S. Patent No. 10,316,073, the contents of which are incorporated herein by reference in their entirety. The increased affinity of efgartigimod for FcRn at both acidic and physiological pH results in blocking FcRn-mediated recirculation of IgG.

[0163] Efgartigimod has a molecular weight of about 54 kDa, which is about one third of the molecular weight of full-length IgG (MW about 150 kDa). Thus, 10 mg of efgartigimod is about 185 nmol, so that a dose of 10 mg of efgartigimod / kg body weight corresponds to about 185 nmol of efgartigimod / kg body weight and a dose of 25 mg of efgartigimod / kg body weight corresponds to about 462.5 nmol of efgartigimod / kg body weight. In contrast, a dose of 10 mg of full-length IgG antibody / kg body weight corresponds to about 67 nmol / kg body weight. Furthermore, a fixed dose of 1000 mg of efgartigimod corresponds to a fixed dose of about 18500 nmol of efgartigimod, while a fixed dose of 2000 mg of efgartigimod corresponds to a fixed dose of about 37,000 nmol of efgartigimod.

[0164] Due to its increased affinity for FcRn at both acidic and neutral pH, efgartigimod blocks the formation of FcRn / IgG complexes, which leads to the degradation of endogenous IgG, including the autoantibodies that cause IgG-mediated autoimmune diseases. This blockade of FcRn by efgartigimod results in a rapid and profound reduction in autoantibody levels, which is the basis of a therapeutic strategy for the treatment of autoimmune indications where IgG autoantibodies are expected to have a central role in disease pathology, e.g., conditions such as myositis.

[0165] Efgartigimod is in development for both intravenous (IV) and subcutaneous (SC) routes of administration. For SC administration, in certain embodiments, efgartigimod may be administered alone. Alternatively, for SC administration, in certain embodiments, efgartigimod may be administered co-formulated with hyaluronidase, such as, in particular, rHuPH20. Co-formulated materials would allow for larger volumes of SC dosing.

[0166] rHuPH20 is the active ingredient in Halozyme's commercial product, HYLENEX® Recombinant (Hyaluronidase Human Injection), called HYLENEX®, which was approved by the FDA for commercial use in the United States in December 2005. HYLENEX® is a tissue permeability modifier indicated as an adjuvant in SC fluid administration to achieve hydration, to increase dispersion and absorption of other injected medications, and in SC urography to improve resorption of radiopaque agents.

[0167] rHuPH20 is the recombinant enzyme human hyaluronidase produced by genetically engineered Chinese hamster ovary (CHO) cells containing a deoxyribonucleic acid plasmid encoding a soluble fragment of human hyaluronidase (occipital protein 20 [PH20]).

[0168] HZ202 rHuPH20 DS is currently registered in HYLENEX® and other biologic products that are co-formulated with rHuPH20 DS, and therefore, in certain embodiments, HZ202 rHuPH20 DS is used in an efgartigimod / rHuPH20 co-formulation for SC administration (i.e., efgartigimod PH20 SC).

[0169] SC injection volumes are typically limited to 2.5 mL due to concerns regarding injection pain associated with larger volumes. rHuPH20 has been shown to provide a solution to the volume limitations associated with fast SC injections. rHuPH20 acts locally and transiently to depolymerize hyaluronan, a gel-like substance found in the subcutaneous layer of the skin. This results in a decrease in resistance to fluid flow, which can increase the dispersion and absorption of injected medications and fluids, allowing larger volumes to be injected with limited swelling or pain. rHuPH20 has been shown to allow for rapid absorption of relatively large volumes (10 mL) when administered SC. Shpilberg O et al., Br J Cancer. 2013;109(6):1556-1561. Little injection site swelling was observed when 10 mL of IgG solution was administered SC with rHuPH20 at 2000 U / mL, whereas significant injection site swelling was observed when 10 mL of IgG solution was injected without rHuPH20. Shpilberg O et al.,Br J Cancer.2013;109(6):1556-1561.

[0170] rHuPH20 acts transiently and is not absorbed systemically. It has been shown not to provide long-term local activity. rHuPH20 has a half-life of less than 30 minutes in the skin. Hyaluronan levels in the subcutaneous tissue return to normal within 24-48 hours due to the rapid natural turnover of hyaluronan.

[0171] rHuPH20 is approved in the United States and Europe for SC administration in co-formulation with other active ingredients (RITUXAN HYCELA® / MABTHERA® SC [rituximab], and HERCEPTIN HYLECTATM / HERCEPTIN® SC [trastuzumab] for non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL)) at an enzyme concentration of 2000 U / mL and injectable volumes ranging from 5 to 13.4 mL.

[0172] In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 300 mg to about 6000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 750 mg to about 3000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 1000 mg to about 2500 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of about 1000 mg to about 2000 mg.

[0173] In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 300 mg to about 6000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 750 mg to about 3000 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 1000 mg to about 2500 mg. In some embodiments, the pharmaceutical preparation comprises an FcRn antagonist in an amount of 1000 mg to about 2000 mg.

[0174] In some embodiments, the pharmaceutical formulation comprises about 1000 mg or about 2000 mg of the FcRn antagonist. In some embodiments, the pharmaceutical formulation comprises 1000 mg or 2000 mg of the FcRn antagonist. In some embodiments, the FcRn antagonist is efgartigimod.

[0175] In some embodiments, the pharmaceutical formulation comprises efgartigimod in an amount of about 800 mg to about 1200 mg. In some embodiments, the pharmaceutical formulation comprises about 1000 mg of efgartigimod. In some embodiments, the pharmaceutical formulation comprises 1000 mg of efgartigimod.

[0176] In some embodiments, the pharmaceutical formulation comprises about 10 mg / mL to about 200 mg / mL of efgartigimod.In some embodiments, the pharmaceutical formulation comprises about 10 mg / mL to about 200 mg / mL of efgartigimod.

[0177] In some embodiments, the pharmaceutical formulation comprises about 20 mg / mL of efgartigimod. In some embodiments, the pharmaceutical formulation comprises about 20 mg / mL of efgartigimod.

[0178] In some embodiments, the pharmaceutical formulation comprises about 180 mg / ml of efgartigimod. In some embodiments, the pharmaceutical formulation comprises about 180 mg / ml of efgartigimod.

[0179] In some embodiments, the pharmaceutical formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

[0180] Hyaluronidase can be present in the pharmaceutical formulation in any suitable amount. In one embodiment, the amount of hyaluronidase enzyme is about 1000 U / ml to about 3000 U / ml. In one embodiment, the amount of hyaluronidase enzyme is about 1000 U / mL, about 1500 U / mL, about 2000 U / mL, about 2500 U / mL, or about 3000 U / mL. In one embodiment, the amount of hyaluronidase enzyme is 2000 U / mL.

[0181] In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of about 11,000 U. In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of 11,000 U.

[0182] In any of the above embodiments, the pharmaceutical formulation may be in a unit dosage form.

[0183] In one embodiment, the unit dosage form comprises the FcRn antagonist as a dry formulation for dissolution, such as a lyophilized powder, freeze-dried powder, or water-free concentrate, In one embodiment, the dry formulation is contained in a hermetically sealed container, such as a vial, ampoule, or sachet.

[0184] In one embodiment, the unit dosage form comprises an FcRn antagonist as a liquid formulation, e.g., an injection or infusion solution, hi one embodiment, the liquid formulation is contained in a sealed container such as a vial, a sachet, a pre-filled syringe, a pre-filled auto-injector, or a cartridge for a reusable syringe or applicator.

[0185] In one embodiment, a unit dosage per vial may contain 0.5 ml, 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 15 ml, or 20 ml of FcRn antagonist in the range of about 500 to about 2500 mg or about 1000 mg to about 2000 mg. In one embodiment, these preparations can be adjusted to the desired concentration by adding a sterile diluent to each vial.

[0186] The formulations disclosed herein include bulk drug compositions useful for manufacturing pharmaceutical compositions (e.g., compositions suitable for administration to a subject or patient) that can be used to prepare unit dosage forms. In one embodiment, the compositions of the invention are pharmaceutical compositions. Such compositions comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents (e.g., an FcRn antagonist of the invention or other prophylactic or therapeutic agent) and a pharma- ceutically acceptable carrier. In one embodiment, the pharmaceutical composition is formulated to be suitable for subcutaneous administration to a subject.

[0187] method In one aspect, a method for treating myositis using an FcRn antagonist is provided. In certain embodiments, the myositis is one or more of the following: immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), juvenile dermatomyositis (JDM), polymyositis (PM), and antisynthetase syndrome (ASyS). In certain embodiments, the myositis is IMNM. In certain embodiments, the FcRn antagonist is efgartigimod. An important goal and feature of the methods disclosed herein is the reduction or even elimination of the use of potentially toxic drugs such as corticosteroids (e.g., prednisone) in the treatment of myositis. Another important goal and feature of the methods disclosed herein is the rapid onset of disease control. Yet another important goal and feature of the methods disclosed herein is the achievement of long-term complete remission with minimal treatment, preferably without the use of potentially toxic drugs such as corticosteroids (e.g., prednisone). Effective treatment of myositis using an FcRn antagonist may include at least one of the elements of the group consisting of improved muscle strength, stabilization of muscle strength, improved QoL (quality of life), improved pulmonary function, stabilization of pulmonary function, safety and / or tolerability of the FcRn antagonist, steroid sparing effect, and improvement of pain.

[0188] In certain embodiments, myositis may be characterized as severe or non-severe as classified by Physician's Global Assessment of Disease Activity (MDGA). In certain embodiments, myositis may be characterized as severe myositis (e.g., an MDGA score of 5 or greater). In other embodiments, myositis may be characterized as non-severe myositis (e.g., an MDGA score of less than 5).

[0189] In some embodiments, myositis may be characterized by an MMT8 score of less than 142 / 150. In some embodiments, myositis may be characterized by one or more of the following: an MDGA score of 2 or greater, a PGA score of 2 or greater, an extramuscular global score of 2 or greater, a HAQ-DI score of 0.25 or greater, and muscle enzymes (such as CK, aldolase, lactate dehydrogenase (LDH), AST, or ALT) greater than or equal to 1.5 times the upper limit of normal.

[0190] In some embodiments, the myositis is IMNM and may be characterized as anti-signal recognition particle (SRP) positive, anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) positive, or both anti-SRP positive and anti-HMGCR positive.

[0191] In some embodiments, the myositis is PM (including ASyS) and may be characterized as being positive for at least one anti-aminoacyl-tRNA synthetase antibody (such as anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and / or anti-OJ antibody).

[0192] In some embodiments, the myositis is DM or JDM and may be characterized by active DM skin rash (such as Gottron papules, Gottron sign, and / or a heliotrope rash).

[0193] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 200 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 300 mg to about 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 750 mg to about 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2500 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0194] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 200 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 300 mg to 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2500 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0195] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20 mg, about 50 mg, about 100 mg, about 200 mg, about 250 mg, about 300 mg, about 500 mg, about 750 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 2500 mg, about 3000 mg, about 4000 mg, about 5000 mg, about 6000 mg, about 7000 mg, about 8000 mg, about 9000 mg, about 10,000 mg, about 11,000 mg, about 12,000 mg, about 13,000 mg, about 14,000 mg, about 15,000 mg, about 16,000 mg, about 17,000 mg, about 18,000 mg, about 19,000 mg, or about 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0196] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0197] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0198] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 2 mg / kg to 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 3 mg / kg to 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0199] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, The FcRn antagonist is administered at a dose of about 50 mg / kg, about 55 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, about 75 mg / kg, about 80 mg / kg, about 85 mg / kg, about 90 mg / kg, about 95 mg / kg, about 100 mg / kg, about 110 mg / kg, about 120 mg / kg, about 130 mg / kg, about 140 mg / kg, about 150 mg / kg, about 160 mg / kg, about 170 mg / kg, about 180 mg / kg, about 190 mg / kg, or about 200 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0200] In some embodiments, the FcRn antagonist is administered at 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, The FcRn antagonist is administered at a dose of 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, 110 mg / kg, 120 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 170 mg / kg, 180 mg / kg, 190 mg / kg, or 200 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0201] In some embodiments, the FcRn antagonist is administered intravenously. In some embodiments, the FcRn antagonist is administered intravenously once every week, once every two weeks, once every three weeks, once every four weeks, once every month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0202] In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 0.2 mg / kg to about 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 2 mg / kg to about 200 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 2 mg / kg to about 120 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 3 mg / kg to about 60 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 25 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0203] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, The FcRn antagonist is administered intravenously once every week or once every two weeks at a dose of about 55 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, about 75 mg / kg, about 80 mg / kg, about 85 mg / kg, about 90 mg / kg, about 95 mg / kg, about 100 mg / kg, about 110 mg / kg, about 120 mg / kg, about 130 mg / kg, about 140 mg / kg, about 150 mg / kg, about 160 mg / kg, about 170 mg / kg, about 180 mg / kg, about 190 mg / kg, or about 200 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0204] In some embodiments, the FcRn antagonist is administered at 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 ...5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg, 5 mg / kg 5mg / kg, 60mg / kg, 65mg / kg, 70mg / kg, 75mg / kg, 80mg / kg, 85mg / kg, 90mg / kg, 95mg / kg, 100mg / kg, 110mg / kg, 120mg / kg, 130mg / kg, 140mg / kg, 150mg / kg, 160mg / kg, 170mg / kg, 180mg / kg, 190mg / kg, or 200mg / kg administered intravenously once every week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0205] In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 30 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 25 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 15 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 20 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 25 mg / kg once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 30 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to 25 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 15 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 20 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 25 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 30 mg / kg, once every week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0206] In some embodiments, the FcRn antagonist is administered subcutaneously. In some embodiments, the FcRn antagonist is administered subcutaneously once every week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0207] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 20 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 100 mg to about 10,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0208] In some embodiments, the FcRn antagonist is administered in an amount of about 20 mg, about 50 mg, about 100 mg, about 250 mg, about 500 mg, about 750 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 3000 mg, about 4000 mg, about 5000 mg, about 6000 mg, about 7000 mg, about 8000 mg, about 9000 mg, about 10,000 mg, about 11,000 mg, or about 12,000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg, about 12,000 mg, about 13,000 mg, about 14,000 mg, about 15,000 mg, about 16,000 mg, about 17,000 mg, about 18,000 mg, about 19,000 mg, or about 20,000 mg once every week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0209] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 20 mg, 50 mg, 100 mg, 250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0210] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 750 mg to about 3000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg to about 2000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg or about 2000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0211] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once per week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0212] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of about 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of about 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is efgartigimod.

[0213] In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 750 mg to about 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 800 mg to about 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1500 mg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1750 mg once weekly. In some embodiments, the FcRn antagonist is efgartigimod.

[0214] In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 750 mg to 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 800 mg to 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once weekly at a fixed dose of about 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1500 mg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1750 mg once weekly. In some embodiments, the FcRn antagonist is efgartigimod.

[0215] In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of about 10 mg / kg to about 25 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of about 10 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of about 15 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of about 20 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of about 25 mg / kg once weekly. In some embodiments, the FcRn antagonist is efgartigimod.

[0216] In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of 10 mg / kg to 25 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of 10 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of 15 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of 20 mg / kg once weekly. In some embodiments, the FcRn antagonist is administered subcutaneously at a dose of 25 mg / kg once weekly. In some embodiments, the FcRn antagonist is efgartigimod.

[0217] In some embodiments, the FcRn antagonist is administered intravenously first, then subcutaneously. In some embodiments, the FcRn antagonist is administered intravenously first, then subcutaneously at a fixed dose of 100 mg to 10,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered intravenously first, then subcutaneously at a fixed dose of 1000 mg or 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0218] In some embodiments, one or more doses of FcRn antagonist are administered intravenously, followed by subcutaneous administration of a subsequent dose of FcRn antagonist. In some embodiments, one or more doses of FcRn antagonist are administered intravenously, followed by subcutaneous administration of a subsequent dose of FcRn antagonist at a fixed dose of 100 mg to 10,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, one or more doses of FcRn antagonist are administered intravenously, followed by subcutaneous administration of a subsequent dose of FcRn antagonist at a fixed dose of 1000 mg or 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0219] In some embodiments, the FcRn antagonist is administered for no more than 6, 12, 24, 39, or 52 weeks. In some embodiments, the FcRn antagonist is administered for no more than 24 weeks. In some embodiments, the FcRn antagonist is administered for no more than 52 weeks. In some embodiments, the FcRn antagonist is administered for at least 6, 12, 24, 39, or 52 weeks. In some embodiments, the FcRn antagonist is administered for at least 24 weeks. In some embodiments, the FcRn antagonist is administered for at least 52 weeks.

[0220] In some embodiments, the FcRn antagonist is rozanolixizumab. In some embodiments, rozanolixizumab is administered subcutaneously or intravenously. In some embodiments, rozanolixizumab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

[0221] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg mg / kg, approximately 25 mg / kg, approximately 26 mg / kg, approximately 27 mg / kg, approximately 28 mg / kg, approximately 29 mg / kg, approximately 30 mg / kg, approximately 31 mg / kg, approximately 32 mg / kg, approximately 33 mg / kg, approximately 34 mg / kg, approximately 35 mg / kg, approximately 36 mg / kg, approximately 37 m g / kg, approximately 38 mg / kg, approximately 39 mg / kg, approximately 40 mg / kg, approximately 41 mg / kg, approximately 42 mg / kg, approximately 43 mg / kg, approximately 44 mg / kg, approximately 45 mg / kg, approximately 46 mg / kg, approximately 47 mg / kg, approximately 48 mg / kg, approximately 49 mg / kg, approximately 50 mg / kg, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg kg, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / k g, about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once weekly.

[0222] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about

[0043] The compound is administered once every two weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0223] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about

[0043] The compound is administered once every three weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0224] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about

[0043] The compound is administered once every four weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0225] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / kg kg, approximately 51mg / kg, approximately 52mg / kg, approximately 53mg / kg, approximately 54mg / kg, approximately 55mg / kg, approximately 56mg / kg, approximately 57mg / kg, approximately 58mg / kg, approximately 59mg / kg, approximately 60mg / kg, approximately 61mg / kg, approximately 62mg / kg, approximately 63mg / k g, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg , about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0226] In some embodiments, the FcRn antagonist is nipocalimab. In some embodiments, nipocalimab is administered subcutaneously or intravenously. In some embodiments, nipocalimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

[0227] In some embodiments, nipocalimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 6 kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / k g, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg , about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once weekly.

[0228] In some embodiments, nipocalimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 6 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every two weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0229] In some embodiments, nipocalimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 6 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every three weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0230] In some embodiments, nipocalimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 6 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every four weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0231] In some embodiments, nipocalimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 6 kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0232] In some embodiments, the FcRn antagonist is olilanolimab. In some embodiments, olilanolimab is administered subcutaneously or intravenously. In some embodiments, olilanolimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

[0233] In some embodiments, orilanolimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about / kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / kg kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg kg, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / k g, about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once weekly.

[0234] In some embodiments, orilanolimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about

[0043] The compound is administered once every two weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0235] In some embodiments, orilanolimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about

[0043] The compound is administered once every three weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0236] In some embodiments, orilanolimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about

[0043] The compound is administered once every four weeks at a dose of about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0237] In some embodiments, orilanolimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about / kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0238] In some embodiments, orilanolimab is administered intravenously at a dose of about 30 mg / kg once weekly for three weeks, then at a dose of 10 mg / kg intravenously every other week.

[0239] In some embodiments, the FcRn antagonist is batoclimab. In some embodiments, batoclimab is administered subcutaneously or intravenously. In some embodiments, batoclimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

[0240] In some embodiments, batoclimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / k g, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg , about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once weekly.

[0241] In some embodiments, batoclimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every two weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0242] In some embodiments, batoclimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every three weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0243] In some embodiments, batoclimab is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7

[0043] The compound is administered once every four weeks at a dose of about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0244] In some embodiments, batoclimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0245] In one embodiment, the subject has been previously treated with a corticosteroid and / or an immunosuppressant and / or an antimalarial. In one embodiment, the subject has been previously treated with prednisone. In one embodiment, the corticosteroid is an oral corticosteroid. Examples of oral corticosteroids include, but are not limited to, betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, prednisolone, and triamcinolone. In one embodiment, the immunosuppressant is selected from methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mixolibin. In one embodiment, the antimalarial is selected from hydroxychloroquine, quinacrine, or chloroquine.

[0246] In one embodiment, the subject has been previously treated with prednisone at a dose of 5 mg / day to 20 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 7.5 mg / day to 15 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 8 mg / day to 15 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 10 mg / day to 15 mg / day.

[0247] In one embodiment, the method further comprises administering to the subject an effective amount of a corticosteroid and / or an immunosuppressant and / or an antimalarial. In one embodiment, the corticosteroid is an oral corticosteroid. Examples of oral corticosteroids include, but are not limited to, betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, prednisolone, and triamcinolone. In one embodiment, the immunosuppressant is selected from methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mixolibin. In one embodiment, the antimalarial is selected from hydroxychloroquine, quinacrine, or chloroquine.

[0248] In one embodiment, the effective amount of corticosteroid is administered in a dose of 2.5 mg / day to 20 mg / day. In one embodiment, the effective amount of corticosteroid is administered in a dose of 5 mg / day to 20 mg / day. In one embodiment, the effective amount of corticosteroid is administered in a dose of 7.5 mg / day to 20 mg / day. In one embodiment, the effective amount of corticosteroid is administered in a dose of 8 mg / day to 15 mg / day. In one embodiment, the effective amount of corticosteroid is administered in a dose of 10 mg / day to 15 mg / day. In one embodiment, the effective amount of corticosteroid is administered in a dose of about 20 mg per day. In one embodiment, the effective amount of corticosteroid is administered in a dose of about 10 mg per day. In one embodiment, the effective amount of corticosteroid is administered in a dose of about 7.5 mg per day. In one embodiment, the effective amount of corticosteroid is administered in a dose of about 5 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 2.5 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 5 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 3 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 2 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 1 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.5 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.4 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.3 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.25 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.2 mg / kg / day. In one embodiment, the effective amount of a corticosteroid is administered at a dose of about 0.1 mg / kg / day.

[0249] In one embodiment, the corticosteroid dosing regimen is tapered in the subject after treatment with the FcRn antagonist. In one embodiment, tapering the corticosteroid regimen is reducing the dose of the corticosteroid or reducing the dosing frequency. In one embodiment, the corticosteroid dose is reduced after 16 weeks of treatment with the FcRn antagonist. In one embodiment, the corticosteroid dose is reduced after 24 weeks of treatment with the FcRn antagonist. In one embodiment, if the corticosteroid dose is administered to the subject at more than 5 mg per day before the corticosteroid dose is reduced, the corticosteroid dose is reduced after 16 weeks of treatment with the FcRn antagonist. In one embodiment, if the corticosteroid dose is administered to the subject at more than 5 mg per day before the corticosteroid dose is reduced, the corticosteroid dose is reduced after 24 weeks of treatment with the FcRn antagonist. In one embodiment, if the subject is administered a dose of more than 7.5 mg per day before the corticosteroid dose is reduced, the corticosteroid dose is reduced after 16 weeks of treatment with an FcRn antagonist. In one embodiment, if the subject is administered a dose of more than 7.5 mg per day before the corticosteroid dose is reduced, the corticosteroid dose is reduced after 24 weeks of treatment with an FcRn antagonist. In some embodiments, the prednisone dose is reduced by 2.5 mg / day (or equivalent OCS) after 16 weeks of treatment with an FcRn antagonist. In some embodiments, the prednisone dose is reduced by 2.5 mg / day (or equivalent OCS) after 24 weeks of treatment with an FcRn antagonist. In some embodiments, each daily dose of prednisone (or equivalent OCS) is maintained for at least 2 weeks before the dose is further reduced. In some embodiments, each daily dose of prednisone (or equivalent OCS) is maintained for at least 3 weeks before the dose is further reduced. In some embodiments, each daily dose of prednisone (or equivalent OCS) is maintained for at least 4 weeks before the dose is further reduced.In some embodiments, each daily dose of prednisone (or equivalent OCS) is maintained for four weeks before the dose is further reduced.

[0250] In one embodiment, the first corticosteroid tapering dose can be a dose reduction of less than 2.5 mg. In one embodiment, for a baseline dose of 18-20 mg, the first reduced dose is 17.5 mg. In one embodiment, for a baseline dose of 16-17.5 mg, the first reduced dose is 15 mg. In one embodiment, for a baseline dose of 13-15 mg, the first reduced dose is 12.5 mg. In one embodiment, for a baseline dose of 11-12.5 mg, the first reduced dose is 10 mg. In some embodiments, for a baseline dose of 8-9 mg, the first reduced dose is 7.5 mg. In one embodiment, for a baseline dose of 6-7 mg, the first reduced dose is 5 mg. In some embodiments, the corticosteroid dose is maintained for 4 weeks before the dose is further reduced. In some embodiments, the corticosteroid dose is maintained for 4 weeks and then reduced by 2.5 mg. In some embodiments, each corticosteroid tapering dose is maintained for 4 weeks and then further reduced by 2.5 mg. In some embodiments, each corticosteroid tapering dose is maintained for 4 weeks and then further reduced by 2.5 mg until the corticosteroid dose is 5 mg or less prednisone / day or equivalent. In some embodiments, each corticosteroid tapering dose is maintained for 4 weeks and then further reduced by 2.5 mg until the corticosteroid dose is zero (i.e., cessation of corticosteroid therapy).

[0251] In some embodiments, the corticosteroid is administered at 20 mg or less of prednisone / day or equivalent. In some embodiments, the corticosteroid dose is 7.5 mg or less of prednisone / day or equivalent. In some embodiments, the corticosteroid dose is 5 mg or less of prednisone / day or equivalent.

[0252] In some embodiments, the FcRn antagonist is administered in the induction phase and the maintenance phase. In certain embodiments, during the induction phase, the FcRn antagonist is administered once a week or more frequently, for example, twice a week or every other day. In certain embodiments, during the induction phase, the FcRn antagonist is administered less frequently than once a week, for example, every other week. In certain embodiments, (i) during the induction phase, the FcRn antagonist is administered once a week concomitantly with a corticosteroid and / or an immunosuppressant and / or an antimalarial agent, and (ii) during the maintenance phase, the dose of the FcRn antagonist is reduced and / or the dosing interval of the FcRn antagonist is extended, for example, to once every two weeks, with or without a concomitant corticosteroid and / or an immunosuppressant and / or an antimalarial agent. In some embodiments, during the maintenance phase, the dose of the corticosteroid is decreased and / or the corticosteroid dosing interval is extended. In some embodiments, (i) during the induction phase, the FcRn antagonist is administered once every week at a dose of 1000 mg, and (ii) during the maintenance phase, the FcRn antagonist is administered once every two weeks at a dose of 1000 mg.

[0253] In one embodiment, the subject has a serum level of a pathogenic IgG autoantibody associated with myositis (e.g., myositis-associated antibody (MAA) or myositis-specific antibody (MSA)). In one embodiment, the pathogenic IgG autoantibody is an anti-HMGCR antibody, an anti-SRP antibody, or an anti-aminoacyl-tRNA synthetase antibody. In one embodiment, the level of pathogenic IgG autoantibody is measured by ELISA or addressable laser bead immunoassay (ALBIA). In one embodiment, the serum level of pathogenic IgG autoantibody is compared to a baseline level in the subject.

[0254] In one embodiment, the myositis is immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), juvenile dermatomyositis (JDM), polymyositis (PM), or antisynthetase syndrome (ASyS). In some embodiments, the myositis is IMNM.

[0255] In some embodiments, the treatment of myositis is characterized by a reduction in autoantibodies. In some embodiments, the autoantibodies are anti-SRP autoantibodies. In some embodiments, the prevalence of anti-SRP autoantibodies is reduced by at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% after administration of one or more of the treatments described herein. In some embodiments, anti-SRP autoantibodies are undetectable in the subject after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod. In some embodiments, the myositis is IMNM.

[0256] In some embodiments, the autoantibody is an anti-HMGCR autoantibody. In some embodiments, the prevalence of anti-HMGCR autoantibody is reduced by at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% after administration of one or more of the treatments described herein. In some embodiments, anti-HMGCR autoantibody is undetectable in the subject after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod. In some embodiments, the myositis is IMNM.

[0257] In some embodiments, the treatment of myositis is characterized by a total improvement score (TIS). In some embodiments, the TIS is at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, or at least 70 points after administration of one or more of the treatments described herein. In some embodiments, a minimal clinical improvement (TIS≧20) is observed within 24 weeks, within 12 weeks, or within 6 weeks after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0258] In some embodiments, the treatment of myositis is characterized by an improvement in muscle strength. In some embodiments, the improvement in muscle strength is measured by MMT8. In some embodiments, the MMT8 score increases by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0259] In some embodiments, the treatment of myositis is characterized by a decrease in Patient Global Assessment (PGA) of disease activity. In some embodiments, the PGA is decreased by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0260] In some embodiments, the treatment of myositis is characterized by a decrease in Physician's Global Assessment of Disease Activity (MDGA). In some embodiments, the MDGA is decreased by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0261] In some embodiments, the treatment of myositis is characterized by an improvement in extramuscular global assessment of disease activity. In some embodiments, the extramuscular global assessment of disease activity is improved by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0262] In some embodiments, the treatment of myositis is characterized by an improvement in pain and / or fatigue reported by the subject. In some embodiments, the improvement in pain and / or fatigue in the subject is determined by a subject-reported numerical score (NRS). In some embodiments, the pain and / or fatigue is improved by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0263] In some embodiments, the treatment of myositis is characterized by an improvement in physical function. In some embodiments, the improvement in physical function is determined by HAQ-DI. In some embodiments, the physical function improves by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0264] In some embodiments, the treatment of myositis is characterized by a reduction in muscle necrosis. In some embodiments, muscle necrosis is reduced by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0265] In some embodiments, the treatment of myositis is characterized by muscle fiber regeneration. In some embodiments, muscle fiber regeneration is determined by the presence of centrally-nucleated fibers, and an increase in centrally-nucleated fibers indicates muscle fiber regeneration. In some embodiments, muscle necrosis is increased by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0266] In some embodiments, the treatment of myositis, particularly dermatomyositis (DM), is characterized by a decrease in CDASI. In some embodiments, the CDASI is decreased by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0267] In one aspect, provided herein is a method for monitoring treatment of myositis in a subject following treatment with an FcRn antagonist, the method comprising: a) measuring muscle enzymes, autoantibodies, or both in a blood sample taken from the subject; and b) comparing the level of muscle enzymes, the level of autoantibodies, or both to a reference value associated with an autoantibody-mediated disease in the subject, wherein the subject is in remission from the autoantibody-mediated disease when the muscle enzymes, autoantibodies, or both in the sample are at or below the reference value.

[0268] In one aspect, provided herein is a method for monitoring the effectiveness of a treatment of myositis in a subject following treatment with a first FcRn antagonist, the method comprising: a) measuring in vitro a serum level of a myositis-associated antibody (MAA) or a myositis-specific antibody (MSA) in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the treatment is ineffective; and if the serum level of MAA or MSA in the sample is less than the reference value, the treatment is effective.

[0269] In one aspect, provided herein is a method of treating myositis in a subject receiving a first FcRn antagonist and a corticosteroid dosing regimen, the method comprising: a) administering to the subject an effective amount of a second FcRn antagonist; b) measuring in vitro a serum level of MAA or MSA in a blood sample taken from the subject; and c) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the corticosteroid dosing regimen is maintained, or if the serum level of MAA or MSA is less than the reference value, the corticosteroid dosing regimen is tapered.

[0270] In one aspect, provided herein is a second FcRn antagonist for use in a method of treating myositis in a subject receiving a first FcRn antagonist and a corticosteroid dosing regimen, wherein a) an effective amount of the second FcRn antagonist is administered to the subject, b) a serum level of MAA or MSA is measured in vitro in a blood sample taken from the subject, and c) the serum level of MAA or MSA is compared to a reference value associated with myositis in the subject, and if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the corticosteroid dosing regimen is maintained, and if the serum level of MAA or MSA is less than the reference value, the corticosteroid dosing regimen is tapered.

[0271] In some embodiments, the corticosteroid dosing regimen is tapered to a lower dose or less frequent administration. In one embodiment, the method further comprises administering to the subject an effective amount of a second FcRn antagonist if the serum level of MAA or MSA in the sample is equal to or greater than the reference value. In one embodiment, the method further comprises administering to the subject an effective amount of a second FcRn antagonist if the serum level of MAA or MSA in the sample is equal to or greater than the reference value.

[0272] In one aspect, provided herein is a method for treating myositis in a subject, the method comprising: (a) administering to the subject one or more initial doses of an effective amount of a first FcRn antagonist; and (b) if the serum level of MAA or MSA in the subject after step (a) is equal to or greater than a reference value associated with myositis in the subject, administering to the subject one or more further doses of an effective amount of a second FcRn antagonist, or if the serum level of MAA or MSA in the subject after step (a) is less than a reference value associated with active disease in the subject, discontinuing treatment with the first FcRn antagonist.

[0273] In one aspect, provided herein is an FcRn antagonist for use in a method of treating myositis in a subject, wherein (a) one or more initial doses of an effective amount of a first FcRn antagonist are administered to the subject; and (b) if the serum level of MAA or MSA in the subject after step (a) is equal to or greater than a reference value associated with myositis in the subject, one or more further doses of an effective amount of a second FcRn antagonist are administered to the subject, or if the serum level of MAA or MSA in the subject after step (a) is less than the reference value associated with myositis in the subject, the first FcRn antagonist is discontinued.

[0274] In one embodiment, the effective amount of the first FcRn antagonist is a dose of about 10 mg / kg to about 30 mg / kg administered intravenously.

[0275] In one embodiment, the effective amount of the first FcRn antagonist is a dose of about 750 mg to about 3000 mg administered subcutaneously.

[0276] In one aspect, provided herein is a method for determining whether a subject previously treated for myositis using a first FcRn antagonist requires further treatment with a second FcRn antagonist, the method comprising: a) measuring in vitro the serum level of MAA or MSA in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the subject requires further treatment with the second FcRn antagonist.

[0277] In one aspect, provided herein is a method for treating myositis in a subject, comprising administering to the subject an effective amount of a second FcRn antagonist, wherein the myositis has recurred in the subject after prior therapy with a first FcRn antagonist, and the subject has a serum level of MAA or MSA that is equal to or greater than a reference value associated with myositis in the subject.

[0278] In one aspect, provided herein is a second FcRn antagonist for use in a method of treating myositis in a subject, wherein the myositis has recurred in the subject after prior therapy with a first FcRn antagonist, and the subject has a serum level of MAA or MSA at or above a reference level associated with myositis in the subject.

[0279] In one aspect, provided herein is a method for treating myositis in a subject, comprising administering to the subject an effective amount of a second FcRn antagonist, wherein after prior therapy with a first FcRn antagonist, the myositis recurs in the subject, and the effective amount of the FcRn antagonist is determined based on the serum level of MAA or MSA in a blood sample taken from the subject.

[0280] In one aspect, provided herein is a second FcRn antagonist for use in a method of treating myositis in a subject, wherein the myositis recurs in the subject after prior therapy with a first FcRn antagonist, the method comprising administering to the subject an effective amount of the second FcRn antagonist, wherein the effective amount is determined based on the serum level of MAA or MSA in a blood sample taken from the subject.

[0281] In one aspect, provided herein is a method for monitoring the effectiveness of treatment in a subject following treatment with a first FcRn antagonist, the subject having myositis, the method comprising: a) measuring in vitro a serum level of MAA or MSA in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein if the serum level of MAA or MSA in the sample is equal to or greater than the reference value, the treatment is ineffective, or if the serum level of MAA or MSA is less than the reference value, the treatment is effective.

[0282] In one aspect, provided herein is a method for monitoring remission of myositis in a subject following treatment with a first FcRn antagonist, the method comprising: a) measuring in vitro a serum level of MAA or MSA in a blood sample taken from the subject; and b) comparing the serum level of MAA or MSA to a reference value associated with myositis in the subject, wherein the subject is in remission from myositis if the serum level of MAA or MSA in the sample is at or below the reference value.

[0283] MAA and MSA are typically not present in the serum of healthy individuals (i.e., individuals not suffering from myositis or other autoantibody-mediated diseases), therefore, in one embodiment, the reference value is an undetectable serum level of MAA or MSA.

[0284] In some embodiments, the reference value is about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 109%, 109% of the maximum serum level of MAA or MSA measured in the subject prior to receiving any treatment for myositis. 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%. In one embodiment, the reference value is greater than about 60% of the maximum serum level of MAA or MSA measured in the subject prior to receiving any treatment for myositis.

[0285] In some embodiments, the reference value is 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 109%, 109%, 108%. 3%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%. In one embodiment, the reference value is greater than 60% of the maximum serum level of MAA or MSA measured in the subject prior to receiving any treatment for myositis.

[0286] In some embodiments, the reference value is about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 109%, 109% of the mean serum level of MAA or MSA measured in the subject prior to receiving any treatment for myositis. 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%. In one embodiment, the reference value is greater than about 60% of the mean serum level of MAA or MSA measured in subjects prior to receiving any treatment for myositis.

[0287] In one embodiment, the reference value is 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43% of the mean serum level of MAA or MSA measured in the subject prior to receiving any treatment for myositis. , 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%. In one embodiment, the reference value is greater than 60% of the mean serum level of MAA or MSA measured in subjects prior to receiving any treatment for myositis.

[0288] In one embodiment, the reference value is about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81% or more lower than the lowest serum level of MAA or MSA measured in a subject following treatment with a first FcRn antagonist for myositis. 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89% or 90% higher.

[0289] In one embodiment, the reference value is 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 109, 109, 104%, 105%, 106%, 107, 108, 109, 109, 102, 103, 104, 105, 106, 107, 108, 109, 10 2%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90% higher.

[0290] In one embodiment, the reference value is about 2-fold, 2.1-fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold, 3.5-fold, 3.6-fold, 3.7-fold, 3.8-fold, 3.9-fold, 3.10-fold, 3.12-fold, 3.14-fold, 3.16-fold, 3.18-fold, 3.19-fold, 3.21-fold, 3.22-fold, 3.23-fold, 3.24-fold, 3.25-fold, 3.26-fold, 3.27-fold, 3.28-fold, 3.29-fold, 3.30-fold, 3.31-fold, 3.32-fold, 3.3334-fold, 3.34-fold, 3.35-fold, 3.36-fold, 3.37-fold, 3.38-fold, 3.39-fold, 3.40-fold, 3.41-fold, 3.42-fold, 3.43-fold, 3.44-fold, 3.45-fold, 3.46-fold, 3.47-fold, 3.48-fold, 3.49-fold, 3.50-fold, 3.51-fold, 3.52-fold, 3.53-fold, 3.54-fold, 3.55-fold, 3.56-fold, 3.57-fold, 3.58-fold, 3.59-fold, 3.6 3.8x, 3.9x, 4x, 4.1x, 4.2x, 4.3x, 4.4x, 4.5x, 4.6x, 4.7x, 4.8x, 4.9x, 5x, 5.1x, 5.2x, 5.3x, 5.4x, 5.5x, 5.6x, 5.7x, 5.8x, 5.9x, 6x, 6.1x, 6.2x, 6.3x, 6.4x, 6.5x, 6.6x, 6.7x, 6.8x, or 6.9x higher.

[0291] In one embodiment, the reference value is 2-fold, 2.1-fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold, 3.5-fold, 3.6-fold, 3.7-fold, 3.8-fold, 3.9-fold, 3.10-fold, 3.12-fold, 3.14-fold, 3.16-fold, 3.18-fold, 3.19-fold, 3.20-fold, 3.21-fold, 3.22-fold, 3.23-fold, 3.24-fold, 3.25-fold, 3.26-fold, 3.27-fold, 3.28-fold, 3.29-fold, 3.30-fold, 3.31-fold, 3.32-fold, 3.3334-fold, 3.34-fold, 3.35-fold, 3.36-fold, 3.37-fold, 3.38-fold, 3.39-fold, 3.40-fold, 3.41-fold, 3.42-fold, 3.43-fold, 3.44-fold, 3.45-fold, 3.46-fold, 3.47-fold, 3.48-fold, 3.49-fold, 3.50-fold, 3.51-fold, 3.52-fold, 3.53-fold, 3.54-fold, 3.55-fold, 3.56-fold, 3.57-fold, 3.58-fold, 3.59 .8x, 3.9x, 4x, 4.1x, 4.2x, 4.3x, 4.4x, 4.5x, 4.6x, 4.7x, 4.8x, 4.9x, 5x, 5.1x, 5.2x, 5.3x, 5.4x, 5.5x, 5.6x, 5.7x, 5.8x, 5.9x, 6x, 6.1x, 6.2x, 6.3x, 6.4x, 6.5x, 6.6x, 6.7x, 6.8x, or 6.9x higher.

[0292] In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 10 mg / kg to about 30 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 10 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 15 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 20 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 25 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with the first FcRn antagonist at a dose of about 30 mg / kg administered intravenously.

[0293] In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 10 mg / kg to about 30 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 10 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 15 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 20 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 25 mg / kg administered intravenously. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 30 mg / kg administered intravenously once weekly.

[0294] In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 10 mg / kg to about 30 mg / kg administered intravenously, once every two weeks. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 10 mg / kg administered intravenously, once every two weeks. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 15 mg / kg administered intravenously, once every two weeks. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 20 mg / kg administered intravenously, once every two weeks. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 25 mg / kg administered intravenously, once every two weeks. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 30 mg / kg administered intravenously, once every two weeks.

[0295] In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 750 mg to about 3000 mg administered subcutaneously. In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 750 mg administered subcutaneously. In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 1000 mg administered subcutaneously. In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 1250 mg administered subcutaneously. In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 1500 mg administered subcutaneously. In one embodiment, the subject was previously treated with the first FcRn antagonist at a dose of about 1750 mg administered subcutaneously.

[0296] In one embodiment, the subject was previously treated with a first FcRn antagonist once weekly at a dose of about 750 mg to about 3000 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once weekly at a dose of about 750 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once weekly at a dose of about 1000 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once weekly at a dose of about 1250 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once weekly at a dose of about 1500 mg administered subcutaneously. In one embodiment, the subject has been previously treated with a first FcRn antagonist once weekly at a dose of about 1750 mg administered subcutaneously.

[0297] In one embodiment, the subject was previously treated with a first FcRn antagonist once every two weeks at a dose of about 750 mg to about 3000 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once every two weeks at a dose of about 750 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once every two weeks at a dose of about 1000 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once every two weeks at a dose of about 1250 mg administered subcutaneously. In one embodiment, the subject was previously treated with a first FcRn antagonist once every two weeks at a dose of about 1500 mg administered subcutaneously. In one embodiment, the subject has been previously treated with a first FcRn antagonist at a dose of about 1750 mg administered subcutaneously once every two weeks.

[0298] In one embodiment, the subject has also been previously treated with a corticosteroid or an immunosuppressant, hi one embodiment, the subject has been previously treated with prednisone.

[0299] In one embodiment, the subject has been previously treated with prednisone at a dose of 5 mg / day to 20 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 7.5 mg / day to 15 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 8 mg / day to 15 mg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 10 mg / day to 15 mg / day.

[0300] In one embodiment, the subject was previously treated with prednisone at a dose of less than 5 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 3 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 2 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 1 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 0.5 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 0.4 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 0.3 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 0.2 mg / kg / day. In one embodiment, the subject was previously treated with prednisone at a dose of less than 0.1 mg / kg / day.

[0301] In one embodiment, the effective amount of the second FcRn antagonist is a higher dose than the previous treatment with the first FcRn antagonist. In one embodiment, the effective amount of the second FcRn antagonist is a lower dose than the previous treatment with the first FcRn antagonist.

[0302] In one embodiment, the effective amount of the second FcRn antagonist is administered more frequently compared to a previous treatment with the first FcRn antagonist, hi one embodiment, the effective amount of the second FcRn antagonist is administered less frequently compared to a previous treatment with the first FcRn antagonist.

[0303] In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 30 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of 10 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of 15 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of 20 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of 25 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of 30 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0304] In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of about 10 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of about 15 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered intravenously at a dose of about 20 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of a second FcRn antagonist is administered intravenously at a dose of about 25 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of a second FcRn antagonist is administered intravenously at a dose of about 30 mg / kg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0305] In one embodiment, an effective amount of the second FcRn antagonist is subcutaneously administered at a fixed dose of about 750 mg to about 3000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is subcutaneously administered at a fixed dose of 1000 mg to 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is subcutaneously administered at a fixed dose of about 750 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1250 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1500 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1750 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0306] In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 1250 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 1500 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks. In one embodiment, an effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of 1750 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 6 weeks.

[0307] In one embodiment, the method further comprises administering to the subject an effective amount of a corticosteroid or an immunosuppressant. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 20 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 15 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 10 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 7.5 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 5 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 4 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 3 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 2 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 1 mg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.5 mg / day.

[0308] In one embodiment, the effective amount of corticosteroid is administered at a dose of about 5 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 3 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 2 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 1 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.75 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.5 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.4 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.3 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.25 mg / kg / day. In one embodiment, the effective amount of corticosteroid is administered at a dose of about 0.2 mg / kg / day. In one embodiment, the effective amount of a corticosteroid is administered at a dose of about 0.1 mg / kg / day. In one embodiment, the effective amount of a corticosteroid is administered at a dose of about 0.05 mg / kg / day.

[0309] In one embodiment, the subject's corticosteroid dosing regimen is tapered based on the serum level of MAA or MSA in the subject with myositis. In one embodiment, tapering the corticosteroid regimen is reducing the dose of the corticosteroid or reducing the dosing frequency. In one embodiment, the tapered corticosteroid dose is 5 mg or less prednisone / day or equivalent. In one embodiment, the tapered corticosteroid dose is less than 2 mg prednisone / kg / day or equivalent. In one embodiment, the tapered corticosteroid dose is about 1.5, 1.0, 0.75, 0.5, or 0.2 mg or less prednisone / kg / day or equivalent. In one embodiment, the tapered corticosteroid dose is less than 0.5 mg prednisone / kg / day or equivalent. In one embodiment, the tapered corticosteroid dose is 0.1 mg or less prednisone / kg / day or equivalent.

[0310] In one embodiment, serum levels of MAA or MSA are measured by ELISA or Addressable Laser Bead Immunoassay (ALBIA).

[0311] In one embodiment, the MSA is selected from the group consisting of anti-SRP, anti-HMGCR, anti-Mi-2, anti-TIF1, anti-SAE, anti-NXP, anti-MDA5, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ.

[0312] In one embodiment, the MAA is selected from the group consisting of anti-PM / Scl75, anti-Ku, anti-snRNP, anti-Ro52 (SSA), anti-Ro / 60 (SSA), and anti-La (SSB).

[0313] In one embodiment, the first FcRn antagonist and the second FcRn antagonist are each the same FcRn antagonist. In one embodiment, the first FcRn antagonist and the second FcRn antagonist are each different FcRn antagonists.

[0314] In one embodiment, the FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In one embodiment, the first FcRn antagonist or the second FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0315] In one embodiment, the FcRn antagonist is efgartigimod. In one embodiment, the first FcRn antagonist or the second FcRn antagonist is efgartigimod.

[0316] In one embodiment, the FcRn antagonist comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3. In one embodiment, the first FcRn antagonist or the second FcRn antagonist comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3.

[0317] In one embodiment, the FcRn antagonist is an anti-FcRn antibody. In one embodiment, the first FcRn antagonist is an anti-FcRn antibody. In one embodiment, the second FcRn antagonist is an anti-FcRn antibody.

[0318] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161).

[0319] In one embodiment, the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist is efgartigimod. In one embodiment, the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3. In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161). In one embodiment, the patient has not been previously treated with efgartigimod.

[0320] In one embodiment, the first FcRn antagonist is selected from the group consisting of rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161), and the second FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively. In one embodiment, the first FcRn antagonist is selected from the group consisting of rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161), and the second FcRn antagonist is efgartigimod. EXAMPLES

[0321] The following examples are offered by way of illustration and not by way of limitation.

[0322] Example 1: Development of a humanized mouse model of immune-mediated necrotizing myopathy (IMNM) Immune-mediated necrotizing myopathies (IMNM) represent a distinct group of inflammatory myopathies. IMNM is characterized by necrosis of skeletal muscle fibers accompanied by high creatine kinase levels and deposition of C5b-9 membrane attack complex (MAC). Most IMNM patients have autoantibodies (aAbs) directed against signal recognition particle (SRP) or hydroxy-3-methylglutaryl-CoaA reductase (HMGCR). In addition to their role as biomarkers, the observed relationship between aAb titers and disease severity provides early indications that these aAbs may be pathogenic and thus central players in IMNM pathophysiology.

[0323] In vitro experiments have shown that anti-SRP and anti-HMGCR aAbs cause muscle fiber atrophy and impair myoblast fusion, thus limiting their regenerative potential. Although they are normally intracellular proteins, SRP and HMGCR proteins can be found on the surface of myotubes exposed to purified patient-derived aAbs. + or anti-HMGCR + Passive transfer of IgG from IMNM patients into mice induces muscle defects accompanied by IgG and complement deposition on muscle fibers, and some degree of muscle necrosis. Disease is less pronounced in complement-deficient mice and is enhanced in mice supplemented with human complement. Together, these results establish a pathogenic role for aAbs in IMNM.

[0324] anti-SRP + or anti-HMGCR + In addition to IMNM patients, passive transfer of IgG from human complement complementing C5-deficient mice now represents a useful humanized model of IMNM to preclinically evaluate the efficacy of candidate therapies.

[0325] Example 2: Examination of the efficacy of prophylactic efgartigimod treatment in a humanized mouse model of immune-mediated necrotizing myopathy (IMNM) Immune-mediated necrotizing myopathy (IMNM) is a severe form of myositis characterized by muscle weakness and elevated serum creatine kinase levels. In biopsies, necrosis / regeneration of skeletal muscle fibers and deposition of C5b-9 membrane attack complex (MAC) are associated with variable levels of immune cell infiltration. The most frequent autoantibodies (aAb) in IMNM patients are directed against hydroxymethylglutaryl-coenzyme A reductase (HMGCR). Anti-HMGCR aAb are pathogenic and induce disease after adoptive transfer into mice by a mechanism that partly involves complement.

[0326] Efgartigimod is an IgG1 Fc fragment that targets the neonatal Fc receptor (FcRn). The ability of efgartigimod to prevent muscle weakness and loss of grip strength in the humanized mouse model of IMNM described in Example 1 was evaluated.

[0327] C57BL / 10 Snj C5 def (C5 - / - ) Mice were treated with total IgG from either anti-HMGCR positive IMNM patients or healthy donors as shown in the scheme in Figure 1. Mice (n=8) were administered 20 mg / kg efgartigimod by subcutaneous injection (SC) and were first injected 1 day prior with 2 mg purified total IgG from an anti-HMGCR positive IMNM patient. All mice received 100 μL of human IgG depleted complement daily to enhance disease induction by human IMNM autoantibodies anti-HMGCR and anti-SRP (Bergua et al. Ann Rheum Dis, 2019, 78(1):p.131-139). To prevent xenoimmunization against human proteins, C5 - / - Mice were pretreated with a single injection of cyclophosphamide (day -1). To demonstrate that anti-HMGCR reduces grip and muscle strength, a control group of mice was injected with 2 mg of purified total IgG from a healthy donor. This should not affect grip and muscle strength. Muscle strength was assessed by measuring gastrocnemius strength during electrical sciatic nerve stimulation (anesthetized animals). Experiments were performed in triplicate.

[0328] Total human IgG was measured on days 0, 2 and 7 using an AssayMax™ Human IgG ELISA kit (Assaypro LLC) according to the manufacturer's protocol.

[0329] Anti-HMGCR autoantibody (aAb) titers were measured on days 0, 3, and 7 using an addressable laser bead immunoassay (ALBIA) that was used to detect and quantify anti-HMGCR autoantibody (aAb) (ALBIA-HMCGR) (Drouot et al., Arthritis Res Ther, 2014, 16(1):p.R39), which is similar to the ALBIA for anti-SRP antibodies (ALBIA-SRP) described by Benveniste et al. (Arthritis Rheum, 2011, 63(7):p.1961-71). Briefly, 10 μg of recombinant HMGCR C domain was diluted with 1.25 × 10 6The beads were coupled to fluorescent Bio-Plex™ COOH-microspheres (Bio-Rad, Hercules, CA, USA). After coupling, the coated beads were used immediately or stored in the dark at −20° C. When indicated, human recombinant SRP or intrinsic factor proteins (Diarect AG, Freiburg, Germany) were used instead of HMGCR as negative controls. Immediately before use, the HMGCR-coated beads were vigorously agitated for 30 s. A 10 μl volume containing 1,250 beads was then added to 100 μl of serum from patients or controls (diluted in Dulbecco's phosphate-buffered saline (DPBS) + 1% fetal bovine serum) in a multiscreen 96-well plate (Millipore, Bedford, MA, USA). The plate was incubated for 2 h at room temperature in the dark on a plate shaker at 650 rpm. Blanks (no serum, secondary antibody only), negative controls (anti-HMGCR negative serum) and positive controls (highly positive human anti-HMGCR Ab serum or rabbit anti-HMGCR Ab with appropriate secondary antibody) were included in all assays. Beads were collected by filtration under vacuum and washed twice with 150 μl DPBS containing 0.1% Tween-20. Biotinylated mouse anti-human IgG or isotype (IgG1, IgG2, IgG3 or IgG4) specific secondary Abs (Southern Biotech, Birmingham, AL, USA) were added at 1 / 2,000 dilution and incubated for 1 h at room temperature under shaking. After washing, beads were incubated with 50 μl streptavidin-R-phycoerythrin (Qiagen, Venlo, The Netherlands) at 1 / 1,000 dilution for 15 min. Finally, the beads were resuspended in 100 μl of DPBS and the mean fluorescence intensity (MFI) was determined on a Bio-Plex™ instrument using Bio-Plex™ Manager software 4.0 (Bio-Rad). The analytical sensitivity of the detection of ALBIA-HMGCR was determined by triplicate doses of serial dilutions of rabbit anti-HMGCR antibody. For each well, the mean MFI and standard deviation (SD) were calculated after subtracting the negative control MFI value.The analytical specificity of detection of ALBIA-HMGCR was determined by using high-level human anti-HMGCR, anti-SRP or anti-intrinsic factor positive sera at 1 / 1,000 dilution. Sera were incubated with purified HMGCR, SRP or intrinsic factor beads for 1 hour at room temperature and MFI was determined as above. Specific inhibition of ALBIA-HMGCR was performed using increasing concentrations of recombinant HMGCR protein with a 1 / 2,000 dilution of anti-HMGCR serum used as 100% reference. Percent inhibition was calculated as (1-(MFI pre-adsorbed serum / MFI serum)) x 100. Homologous and heterologous inhibition of ALBIA-HMGCR was further performed by pre-absorption of three anti-HMGCR, three anti-SRP or three anti-intrinsic factor positive sera with 100 μg / ml of recombinant HMGCR, SRP or intrinsic factor protein. All patient sera were initially assayed at a 1 / 500 dilution. Anti-HMGCR Ab levels were determined at 1 / D dilution using the following formula: (MFI serum / MFI calibrator) x (level of calibrator) x D / 500. The calibrator was a human high positive anti-HMGCR serum (same throughout the study) and its level was arbitrarily set at 100 arbitrary units (AU) / mL. If the sample MFI at 1 / 500 dilution was higher than 80% of the calibrator MFI, further dilutions were performed and the first dilution resulting in an MFI less than 80% of the calibrator MFI was retained for level calculation.

[0330] Prophylactic treatment with 20 mg / kg efgartigimod SC significantly reduced the levels of human IgG and anti-HMGCR in recipient mice (Figure 2). In two of the three experiments, this reduction was already significant on day 2 after human IgG injection. In all three experiments, the reduction in human IgG and anti-HMGCR was significant on day 7.

[0331] Injection of total IgG from anti-HMGCR positive patients resulted in a significant loss of grip strength compared to mice injected with total IgG from healthy donors in two of three replicate experiments (Figure 3). In all three experiments, injection of total IgG from anti-HMGCR positive patients resulted in a significant loss of muscle strength. Prophylactic treatment with 20 mg / kg efgartigimod SC prevented anti-HMGCR-induced loss of grip strength and loss of muscle strength.

[0332] At the end of the life phase of the preventive experiment, mice were sacrificed and muscle tissue was stained with DAPI (nuclei) and anti-human IgG to stain for human IgG bound to muscle tissue. Mice treated with either total IgG from healthy donors or total IgG from IMNM patients positive for anti-HMGCR stained positive for human IgG bound to muscle tissue, whereas mice treated with efgaltigimod and total IgG from IMNM patients positive for anti-HMGCR stained virtually negative for human IgG (Figures 4A-4B). Hematoxylin and eosin (H&E) staining of frozen sections of gastrocnemius muscle isolated from mice treated with total IgG from healthy individuals did not show necrotic cells (Figures 5A-5B). However, muscle tissue from mice treated with total IgG from anti-HMGCR positive IMNM patients showed necrotic cells (triangles). Necrotic myofibers are defined as white and / or hyalinized myofibers combined with loss of sarcolemmal integrity / rough appearance. Prophylactic treatment of anti-HMGCR mice with efgartigimod resulted in less muscle cell necrosis. No regenerating myofibers were detected in mice prophylactically treated with efgartigimod, which may be due to the time point studied (day 7) being too early for regeneration to occur.

[0333] These experiments demonstrate that injection of patient-derived anti-HMGCR causes loss of grip and muscle strength in recipient mice. Muscle weakness is a major symptom suffered by patients with IMNM. Prophylactic treatment with efgartigimod significantly reduced anti-HMGCR levels, thereby preventing anti-HMGCR-induced loss of grip and muscle strength. Furthermore, prophylactic treatment with efgartigimod reduced or prevented muscle fiber necrosis.

[0334] Example 3: Examination of the efficacy of therapeutic efgartigimod treatment in a humanized mouse model of immune-mediated necrotizing myopathy (IMNM) To examine whether efgartigimod could reverse anti-HMGCR-induced muscle weakness and loss of grip strength, we used C57BL6 Rag2 mice. - / - Mice were treated with total IgG from either anti-HMGCR positive IMNM patients or healthy donors as shown in the schemes in Figures 6A-6B. Group A (8 mice) received 2 mg of control IgG from a healthy human donor intraperitoneally (ip). Group B (8 mice) received 2 mg of purified total IgG from an anti-HMGCR positive IMNM patient ip. Group C received 2 mg of purified total IgG from an anti-HMGCR positive IMNM patient ip. At day 8, after onset of disease, mice in group C were treated with efgaltigimod 20 mg / kg SC. Control groups D and E received 2 mg of total IgG from either a healthy donor (group D) or an anti-HMGCR positive IMNM patient (group E). All mice received 100 μL of human IgG deficient complement daily. Rag2 - / - The rationale for using mice is to prevent xenogeneic immunization against human proteins.

[0335] Muscle strength was measured on days 7 (control groups D and E) and 18 (groups A, B and C) by electrical stimulation of the released sciatic nerve as described in Example 2. Grip strength was measured on days 7, 14 and 18 as described in Example 2. Total human IgG was measured on days 0, 7, 11, 15 and 18 using the AssayMax™ human IgG ELISA kit according to the manufacturer's protocol as described in Example 2. Anti-HMGCR titers were measured on days 0, 7, 11, 15 and 18 using an addressable laser bead immunoassay (ALBIA) as described in Example 2 (ALBIA-HMCGR).

[0336] Figure 7 shows that injection of 2 mg of total human IgG results in clearly measurable titers in recipient mice. After an initial treatment with efgartigimod on day 8, human IgG levels were significantly reduced on day 11 and remained reduced on days 15 and 18 after new injections of total human IgG on days 12 and 16 and treatment with efgartigimod on days 11 and 15. Similarly, treatment with efgartigimod on day 8 significantly reduced titers of anti-HMGCR autoantibodies (Figure 8).

[0337] Passive transfer of purified total IgG from an anti-HMGCR positive patient significantly reduced the grip strength of recipient mice already at day 7, whereas mice receiving total IgG from healthy donors retained full grip strength (Figure 9). Treating mice with efgartigimod on day 8 after disease onset fully restored grip strength when measured on days 14 and 18. Similarly, passive transfer of purified total IgG from an anti-HMGCR positive patient resulted in a significant loss of muscle strength when measured on day 7. Treatment with efgartigimod on day 8 resulted in full restoration of muscle strength on day 18 (Figure 10).

[0338] At the end of the life phase of the therapeutic experiment, mice were sacrificed and muscle tissue was stained with DAPI (nuclei) and anti-human IgG to stain for human IgG bound to muscle tissue. Mice treated with either total IgG from healthy donors or total IgG from IMNM patients positive for anti-HMGCR stained positive for human IgG bound to muscle tissue, whereas mice treated with efgaltigimod and total IgG from IMNM patients positive for anti-HMGCR stained substantially less positive for human IgG (Figures 11A-11B). H&E staining of frozen sections of gastrocnemius muscle tissue isolated from mice treated with total IgG from healthy individuals showed no necrotic cells (Figure 12). However, muscle tissue from mice treated with total IgG from anti-HMGCR positive IMNM patients showed necrotic cells (triangles) and regenerating myofibers (stars). Regenerating myofibers appear as cells with one or more nuclei in the center of the cell. Muscle tissue isolated from anti-HMGCR mice treated with efgartigimod at day 8 showed fewer necrotic cells, indicating that treatment with efgartigimod prevents further muscle tissue necrosis in anti-HMGCR treated mice. Quantification of necrotic cells showed that treatment with efgartigimod resulted in significantly fewer necrotic cells compared to mice receiving total IgG from IMNM patients positive for anti-HMGCR that were not treated with efgartigimod (Figure 13). Muscle tissue isolated from anti-HMGCR mice treated with efgartigimod at day 8 showed substantially more regenerated muscle fibers (stars) compared to tissue from anti-HMGCR mice not treated with efgartigimod. Quantification of regenerated muscle fibers showed that treatment with efgartigimod resulted in significantly more regenerated muscle fibers compared to mice receiving total IgG from IMNM patients positive for anti-HMGCR that were not treated with efgartigimod (Figure 14).

[0339] In conclusion, therapeutic treatment of mice with reduced grip and muscle strength due to anti-HMGCR injection results in complete recovery of grip and muscle strength. The efficacy of efgartigimod in this IMNM model is supported by the reduction of pathogenic anti-HMGCR levels, prevention of further muscle fiber necrosis, and regeneration of muscle fibers.

[0340] Example 4: Investigation of the efficacy and safety of efgartigimod in patients with active idiopathic inflammatory myopathy (IIM) Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that include subtypes with various pathologies that primarily target muscle and / or skin as well as other organs. In many subsets, there is a potential role for myositis-specific autoantibodies, most of which are immunoglobulin G (IgG), in disease pathogenesis. Many patients with IIM have persistent impairment of muscle function, which leads to difficulties with activities of daily living and reduced health-related quality of life. The typical treatment for IIM is high-dose glucocorticoids combined with immunosuppressants. The deleterious long-term effects of corticosteroids are well established and include osteoporosis, cataracts, and weight gain. No therapy has been approved by the U.S. Food and Drug Administration (FDA) or European regulatory authorities based on the results of randomized controlled trials for IMNM and PM. Only one approved treatment (10% intravenous immunoglobulin [IVIg]) is available for adults with DM, which was approved based on the results of a randomized controlled clinical trial.

[0341] Neonatal Fc receptor (FcRn) maintains a constant level of IgG in serum by rescuing IgG antibodies from lysosomal degradation after uptake into cells. Efgartigimod is an engineered Fc fragment that inhibits FcRn function by competing with endogenous IgG binding, resulting in reduced IgG recycling and increased IgG degradation. Given the mechanism of action of efgartigimod, which reduces IgG levels, efgartigimod PH20 SC may be beneficial for patients with these specific IIM subtypes.

[0342] ALKIVIA is a global, Phase 2 / 3, randomized, double-blind, placebo-controlled trial of efgartigimod in patients with active IIM. The objective of the study is to investigate the efficacy, safety, tolerability, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod administered subcutaneously (SC; referred to throughout as "efgartigimod PH20 SC") co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) in participants with immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), or polymyositis (PM; including PM with antisynthetase syndrome [ASyS]) in combination with background treatment for idiopathic inflammatory myopathy (IIM).

[0343] To allow for convenient SC injection of the investigational medicinal product (IMP), participants will receive efgartigimod PH20 SC, a solution of efgartigimod co-formulated with rHuPH20, or a matching placebo with the same concentration of rHuPH20. rHuPH20 is currently used co-formulated with approved therapeutic antibodies to facilitate SC injections of volumes greater than 2 mL. As both an IV formulation (efgartigimod IV) and efgartigimod PH20 SC, efgartigimod has been investigated in nonclinical studies in patients with IgG-driven autoimmune diseases (generalized myasthenia gravis [gMG], primary immune thrombocytopenia [ITP], chronic inflammatory demyelinating polyneuropathy, and pemphigus), clinical studies in healthy volunteers, and clinical studies.

[0344] In clinical studies including PD evaluation, efgartigimod IV and efgartigimod PH20 SC effectively reduced IgG antibodies. Available clinical data support the clinical benefit of efgartigimod. Efficacy was demonstrated in a pivotal Phase 3 study in participants with gMG (ARGX-113-1704), and clear signs of efficacy were demonstrated in Phase 2 studies in participants with primary ITP (ARGX-113-1603) or pemphigus (ARGX-113-1701).

[0345] The primary objective of ALKIVIA is to evaluate the efficacy and safety of efgartigimod PH20 subcutaneous (SC) treatment compared to placebo, in addition to standard of care immunomodulatory therapy for the treatment of IIM.

[0346] A. Study Design Overall Design This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, operationally seamless Phase 2 / 3 study to evaluate the efficacy, safety, tolerability, PK, PD, and immunogenicity of efgartigimod PH20 SC in adult participants with active IIM. The study consists of two distinct phases (Phase 2 and Phase 3) with separate cohorts of participants.

[0347] Participants with IIM subtypes of IMNM, DM, and PM will be included in the study. The PM subtype includes patients with ASyS diagnosed under the Connors criteria (i.e., positive serology for anti-tRNA synthetase antibodies and one or more of the following clinical features: Raynaud's phenomenon, arthritis, interstitial lung disease, fever not attributable to another cause, or evidence of myositis). Participants will be classified into the IIM subtype and will meet the specified disease activity parameters.

[0348] At screening, participants must be receiving background IIM treatment of either oral corticosteroids (OCS), one antimalarial, or one protocol-specified immunosuppressant. Participants may receive either a combination of OCS and one antimalarial or OCS and one immunosuppressant. Background treatment for IIM has the required duration of treatment at a stable dose. Screening period is up to 4 weeks, although ad-hoc extensions may be permitted in certain circumstances.

[0349] All screening assessments must be completed and reviewed to ensure potential participants meet all eligibility criteria. After assessments are completed, laboratory results are reported, and, if applicable, eligibility is determined, participants may be randomized. Certain designated screening assessments will be submitted for medical monitor (MM) review prior to the investigator's decision to randomize a participant. The sponsor will also review the designated screening assessments on a subset of participants.

[0350] An independent Data Monitoring Committee (IDMC) has been appointed for this study. In addition, an independent committee, including members with IIM expertise, will be appointed to review previous biopsy data and determine eligibility of participants with a diagnosis of PM or IMNM who had a negative MSA test result (central laboratory) or PM-Sjögren's syndrome overlap (regardless of MSA result).

[0351] Screening will be followed by a 24-week (Phase 2) or 52-week (Phase 3) treatment period during which participants will be randomized to receive either efgartigimod PH20 SC 1000 mg or matching placebo (same concentration of rHuPH20) weekly in addition to background treatment for IIM. Background treatment must follow protocol guidelines during the treatment period.

[0352] In both phases, during the treatment period, participants will receive a fixed dose of IMP (either efgartigimod PH20 SC or matching placebo) every week, except for the last week when they attend the final treatment period visit (i.e., week 24 [visit 7, Phase 2 phase] or week 52 [visit 14, Phase 3 phase]). At the end of the treatment period (i.e., week 24 [visit 7, Phase 2 phase] or week 52 [visit 14, Phase 3 phase]), eligible participants can enroll in the open-label extension (OLE) study ARGX-113-2011, in which all participants will be treated with efgartigimod PH20 SC. Otherwise, participants will continue in the 56-day safety follow-up period.

[0353] During the treatment period, the IMP will be administered at the study site during scheduled visits, which may be administered at the site or in the participant's home by either a home nurse or a fully trained participant / caregiver.

[0354] Phase 2 Approximately 90 adult participants will be enrolled and randomized in the Phase 2 stage of the study, stratified by (1) clinical IIM subtype (IMNM, DM, or PM) and (2) MDGA (severe [MDGA≧5] or non-severe [MDGA<5]). Participants will be randomized in a 1:1 ratio within each stratum to receive either efgartigimod PH20 SC or matching placebo in conjunction with background treatment for IIM. Randomization of approximately 30 participants of each IIM subtype will be targeted. The number of MSA-seronegative participants will be limited to 30% of all participants.

[0355] Final data from Phase 2 will be analyzed to evaluate proof of concept for each disease subtype, support decisions about predictive enrichment, stop the study for futility if efficacy is lacking in all disease subtypes, and confirm the Phase 3 design. The unblinded Phase 2 data will be analyzed and used to recommend adaptations for the Phase 3 design. Only the Phase 2 data will be unblinded; the sponsor and all clinical staff will remain blinded to all Phase 3 data until study completion.

[0356] Phase 3 Recruitment for phase 3 of the study will begin after 90 participants have been randomized in phase 2. The two phases of the study will be conducted in parallel between the start of recruitment for phase 3 and the visit of the last participant in phase 2.

[0357] The design and sample size for the Phase 3 phase will be confirmed after analysis of the Phase 2 data. Approximately 150 adult participants are planned to be enrolled and randomized in the Phase 3 phase, stratified by (1) clinical IIM subtype (IMNM, DM, or PM) and (2) MDGA (severe [MDGA≧5] or non-severe [MDGA<5]). Participants will be randomized in a 1:1 ratio within each stratum to receive either efgartigimod PH20 SC or placebo in conjunction with background treatment for IIM. The number of MSA-seronegative participants will be limited to 30% of all participants.

[0358] For any participant in the Phase 3 phase of the study who has an IIM subtype that is deselected based on data from the Phase 2 phase, the investigator and participant will be notified. The participant will be permanently discontinued from the study and will complete the EDV and safety follow-up visits. However, if the participant is benefiting from the IMP and the investigator determines that continued treatment with the IMP is in the participant's best interest, the participant will have the option to discontinue this study, complete the EDV, and enroll in ARGX-113-2011.

[0359] Rationale for Primary Endpoint The primary endpoint of the study was TIS (assessed by the 2016 American College of Rheumatology [ACR] / European League Against Rheumatism [EULAR] criteria) in the placebo and efgartigimod groups. This score is a weighted sum of improvements in six Core Set Measures for Disease Activity (CSM): MDGA, PGA, MMT8, HAQ-DI, muscle enzymes, and extramuscular disease activity.

[0360] This composition of measurements is designed to allow for the demonstration of efficacy in DM and PM (of which IMNM is a subset). To facilitate combined clinical studies, myositis experts used common response criteria for adult DM / PM, acknowledging the limitation that the ACR / EULAR response criteria were developed using PM diagnosis based on the Bohan and Peter classification criteria, where PM may include different syndromes such as IMNM. These response criteria will still apply to these new entities, given that the data-driven and consensus-driven process used herein includes these syndromes.

[0361] Response criteria are accepted by ACR and EULAR. The TIS includes CSMs scored by both the patient and the physician, taking into account muscle symptoms and extramuscular disease activity and physical function. It also includes objective disease activity parameters, i.e., activity of muscle enzymes. The International Myositis Assessment and Clinical Studies Group (IMACS) recommends a minimal TIS as the primary endpoint for IIM treatment studies. The criteria can be used with the TIS as a continuous outcome measure or as a categorical outcome of improvement (minimal, moderate, or substantial improvement). IMACS considers a minimal TIS threshold to differentiate between treatment groups in clinical studies as clinically significant. IMACS previously developed and partially validated an international consensus on a preliminary definition of improvement in adult and juvenile myositis that combined the CSMs of disease activity and defined the minimal degree of clinically significant change in each of the CSMs. These criteria have been published and have previously been used as endpoints in myositis treatment studies. With the development of the TIS, these criteria / definitions of improvement are no longer recommended for use. To date, several phase 3 studies in patients with IIM have used the TIS as a primary endpoint (NCT02728752, NCT03981744, NCT04044690, and NCT04999020).

[0362] Response rates at the end of the treatment period, time to response, and duration of response in the TIS (secondary endpoints) will provide supportive evidence for the primary endpoint.

[0363] Rationale for inclusion cutoffs Inclusion threshold cutoffs for MDGA, PGA, MMT8, and CDASI were based on previous clinical trials from the past 10-15 years and input from key opinion leaders.

[0364] For MDGA and PGA, the minimum threshold of ≥2 / 10 is based on the study "Rituximab in Myositis," which was the largest clinical study in myositis funded by the National Institutes of Health (NIH). These thresholds were based on discussions among key opinion leaders and underwent a peer review process for the NIH grant. More importantly, these thresholds have been validated by multiple phase 2 and phase 3 clinical studies in participants with IIM, including the ProDERM study, the Acthar study, the Rituximab in Myositis study, and the Tocilizumab clinical study (NCT02043548).

[0365] The MMT8 threshold of 142 / 150 is based on ProDERM research and key opinion leader discussion. An MMT8 below 142 / 150 is identified as a significant weakness that leads to difficulties with activities of daily living and impacts quality of life. Furthermore, a threshold of 142 indicates an approximate mean MMT8 of 125, which is a severe weakness in patients with IIM.

[0366] For eligibility of participants with DM, the CDASI threshold for the Phase 2 stage is set at 7 or higher, which is the established average for mild skin disease activity, and the CDASI threshold for the Phase 3 stage is set at 14 or higher, which is the cutoff for mild to moderate skin disease activity.

[0367] The upper limit of 30% of MSA-seronegative participants corresponds to an estimate of the prevalence of MSA in patients with DM or PM, based on a review of real-world data.

[0368] Rationale for duration of treatment The selected 24-week treatment duration during the Phase 2 phase follows the International Conference on Harmonization (ICH) E1 guideline for the Safety Evaluation of Medicines intended for the long-term treatment of non-life-threatening diseases (chronic or repeated intermittent use longer than 6 months), which states that the number of patients treated for 6 months at the dosage level intended for clinical use should be sufficient to characterize the pattern of adverse drug effects over time.

[0369] The selected 52-week treatment period during the Phase 3 phase accounts for the different IIM subtypes, which are slowly progressive and chronic with waxing and waning disease courses. After confirming the therapeutic effect in the selected disease subtypes, this longer treatment period will allow a more thorough evaluation of the durability of the therapeutic effect and a complete assessment of the primary and key secondary endpoints.

[0370] Dosage Justification The sponsor selected a dose of 1000 mg efgartigimod with rHuPH20 administered as a weekly SC injection for the entire duration of the study as the appropriate dosing regimen for further clinical development.

[0371] Initially, clinical development of efgartigimod was based on IV dosing. Results from phase 1 studies in healthy subjects, phase 2 and 3 studies in patients with gMG, phase 2 studies in patients with primary ITP, phase 2 studies in patients with pemphigus, and PK / PD modeling analysis showed that efgartigimod IV 10 mg / kg administered once weekly achieved near-maximal reduction in serum IgG levels. In interventional studies in patients with gMG or ITP, this dose regimen resulted in clinical efficacy outcomes and reduction in pathogenic autoantibody levels while also maintaining a good safety and tolerability profile.

[0372] The SC route of administration offers convenience to patients with IIM, their caregivers, and healthcare providers because SC injections are easier to administer than IV injections. Additionally, co-formulation of efgartigimod with rHuPH20 allows for higher volumes of SC dosing than typical SC injections because rHuPH20 reduces resistance to fluid flow and increases the dispersion and absorption of injected medication and fluids, allowing larger volumes to be injected with limited skin swelling or pain.

[0373] In this Phase 2 / 3 study, participants will receive efgartigimod PH20 SC as a flat dose (rather than an adjusted dose based on weight change) because this may be more convenient for study participants and site staff and reduce the risk of dosing errors. Results from a PK / PD modeling analysis indicate that efgartigimod PH20 SC 1000 mg once weekly results in serum IgG levels equivalent to a once weekly dose of efgartigimod IV 10 mg / kg. Results from a Phase 1 study comparing the PK and PD properties of efgartigimod IV and SC administration in healthy subjects (ARGX-113-1907) confirmed that four weekly injections of efgartigimod PH20 SC 1000 mg were non-inferior to four weekly injections of efgartigimod IV 10 mg / kg in reducing serum IgG levels. Therefore, the sponsor selected efgartigimod PH20 SC 1000 mg once weekly as the dose regimen for this study.

[0374] A dosing regimen of weekly doses administered throughout the study was selected to achieve and maintain maximal PD efficacy, i.e., steady-state reduction of IgG, including pathogenic autoantibodies. This dosing regimen is expected to maximize the opportunity to induce rapid clinical improvement and sustain this improvement over the 24-week study period. Based on chronic dosing data from nonclinical studies and completed and ongoing clinical studies with efgartigimod PH20 SC, it is expected that this chronic dosing regimen in IIM will be well tolerated.

[0375] B. Study Population Anticipatory approval of protocol deviations from recruitment and enrollment criteria, also known as protocol waivers or exemptions, are not permitted.

[0376] Certain designated screening assessments will be submitted for the Sponsor's review prior to the Investigator's decision to randomize a participant.

[0377] In addition, eligibility (regardless of MSA test result) of participants with a clinical diagnosis of PM or IMNM who had a negative MSA test result (central laboratory) or PM Sjogren's overlap will be adjudicated by an independent committee selected for their expertise in IIM.

[0378] Inclusion criteria Participants were eligible for inclusion in the study only if all of the following criteria applied to them: - At least 18 years of age (or the legal age of consent in the jurisdiction in which the study is conducted) at the time of signing the informed consent; - Definite or probable clinical diagnosis of IIM according to the 2017 EULAR / ACR classification criteria; - History of one of the following medical conditions: A diagnosis of DM or young-onset DM (JDM) (age at disease onset <18 years) fulfilling the 2017 EULAR / ACR criteria for DM or JDM. The date of diagnosis for JDM must not be more than 5 years from the date of screening. A diagnosis of PM (including ASyS) with any of the following: 1) a previous muscle biopsy diagnosis of IIM, 2) a positive test in a central laboratory for at least one anti-aminoacyl-tRNA synthetase MSA (-Jo-1, -PL-7, -PL-12, -EJ, -OJ), The diagnosis of IMNM was made by fulfilling the 2017 European Neuromuscular Center classification criteria with any of the following: 1) anti-signal recognition particle (SRP)-positive (in a central laboratory) myopathy, 2) anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)-positive (in a central laboratory) myopathy, or 3) a prior muscle biopsy with pathological features of IMNM. Participants with PM overlapping with Sjögren's syndrome had to meet the ACR / EULAR 2016 classification criteria for Sjögren's syndrome and would only be included if muscle biopsy did not show any of the following: P62(+) inclusions, rimmed vacuoles, or increased numbers of ragged red fibers and cytochrome oxidase fibers, depending on patient age. Note: Participants with a clinical diagnosis of PM with a negative MSA result and participants with a clinical diagnosis of PM Sjogren's overlap regardless of MSA result will be included after review by an independent committee selected for their IIM expertise. NOTE: Participants with a clinical diagnosis of IMNM with negative anti-SRP and anti-HMGCR results will be included after review by an independent committee selected for their expertise in IMNM. - Active disease defined by the presence of at least one of the following criteria: Abnormal levels of at least one of the following enzymes: CK (≥4 × upper limit of normal [ULN]), aldolase (≥4 × ULN), lactate dehydrogenase (LDH) (≥4 × ULN), AST (≥4 × ULN), or ALT (≥4 × ULN), based on central laboratory results; Electromyogram showing active disease within the past 3 months; Active DM skin rash (Gottron papules, Gottron signs, or heliotrope rash) at screening and baseline, or CDASI ≥ 7 (Phase 2 stage) or ≥ 14 (Phase 3 stage), Muscle biopsy showing active IIM in the past 3 months, Magnetic resonance imaging within the past 3 months showing active inflammation. - Muscle weakness as assessed by an MMT8 score less than 142 / 150 and abnormalities of any two of the other five CSMs: 1) MDGA ≥ 2, 2) PGA ≥ 2, 3) extramuscular global ≥ 2, 4) HAQ-DI ≥ 0.25, 5) muscle enzymes ≥ 1.5 x ULN. -Receive permitted background therapy for IIM. Acceptable background therapy includes: OCS; one antimalarial (hydroxychloroquine, quinacrine, or chloroquine); or one of the following immunosuppressants: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mizoribine. Participants may receive any combination of OCS and up to one antimalarial or OCS and up to one immunosuppressant. Acceptable background therapy must meet the following dose duration(s): 1) Immunosuppressants or antimalarials administered for at least 12 weeks prior to screening, and at least 8 weeks prior to screening, with stable doses thereafter until baseline. Participants who discontinued treatment with immunosuppressants or antimalarials are eligible if their last dose was administered more than 8 weeks prior to screening (except for leflunomide). Participants who discontinued treatment with leflunomide are eligible if their last dose was administered more than 12 weeks prior to screening, unless leflunomide washout treatment was used, in which case participants are eligible if washout treatment was completed more than 4 weeks prior to screening. Note: If participants are receiving Chinese traditional medicines, they should contact the MM to discuss any possible immunosuppressant properties. 2) OCS (≤20 mg prednisone or dose equivalent) initiated >8 weeks prior to screening and at a stable dose >4 weeks prior to screening through baseline. Participants who discontinued treatment with OCS prior to enrollment are eligible if their last dose of steroid was >4 weeks prior to screening. Concurrent stable (>2 weeks prior to screening) use of topical corticosteroid (or other immunomodulator) therapy is permitted if used for a non-IIM-related condition. NOTE: If a participant is receiving both an OCS and an additional medication, the dose durations described for both (1) and (2) must be met. -Contraceptive use by non-sterilized male participants and women of childbearing potential (WOCBP) will be consistent with local regulations, where available, for individuals participating in clinical studies. WOCBP must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline to establish non-pregnant status prior to receiving the IMP. - Able to give signed informed consent, including compliance with the requirements and restrictions stated in the Informed Consent Form (ICF) and in this protocol.

[0379] Exclusion criteria Participants will be excluded from the study if the following criteria apply: - Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening. - A positive COVID-19 polymerase chain reaction (PCR) test less than 72 hours prior to enrollment. COVID-19 testing will only be done if the participant has symptoms or is required by applicable law. In these cases, a negative PCR test (central or local laboratory) within 72 hours prior to enrollment is required and should be done regardless of the participant's vaccination status. - Any other known autoimmune disease which, in the opinion of the investigator, would prevent accurate assessment of the clinical manifestations of IIM or would place the patient at undue risk. -History of malignancy unless deemed cured by adequate treatment, with no evidence of recurrence for ≥3 years prior to first dose of IIM. Adequately treated participants with the following cancers may be included at any time: 1) basal or squamous cell skin cancer, 2) carcinoma in situ of the cervix, 3) carcinoma in situ of the breast, 4) incidental histological findings of prostate cancer (TNM stage T1a or T1b). Note: Patients with IIM are at increased risk for associated malignancies, therefore study participants are encouraged to comply with and be up to date on local recommendations for cancer screening procedures (based on age, sex, and autoantibodies). - Severe muscle damage defined as an overall muscle damage score of >5 on the 10 cm visual analog scale (VAS) scale of the Myositis Damage Index (MDI). - Glucocorticoid-induced myopathy with the primary cause of muscle weakness or permanent weakness related to causes other than IIM, as determined by the investigator. - JDM diagnosed >5 years from screening or with extensive calcifications (defined as calcifications involving the trunk or two extremities) or severe calcifications (indicating calcifications associated with severe loss of function). - Uncontrolled interstitial lung disease or any other uncontrolled IIM condition that, in the investigator's opinion, is likely to require treatment with prohibited medications (e.g., cyclophosphamide) during the study. -Other inflammatory and non-inflammatory myopathies: inclusion body myositis (based on biopsy or if weakness affects finger and / or wrist flexors out of proportion to shoulder abductors), overlapping myositis (connective tissue disease-associated myositis, excluding overlap with Sjogren's syndrome, allowed if biopsy does not show any of the features listed in inclusion criterion 3b), metabolic myopathy, muscular dystrophy or family history of muscular dystrophy, drug-induced or endocrine-induced myositis (excluding statin-induced IMNM), and juvenile myositis (other than JDM). - Has clinically significant illness, recent major surgery (within 3 months of screening), or is intending to undergo surgery during the study, or has any other condition that, in the investigator's opinion, may confound the results of the study or place the patient at undue risk. Known hypersensitivity reaction to IMP or one of its excipients. - Receipt of a live or live-attenuated vaccine <4 weeks prior to screening. Receipt of other types of vaccines at any time prior to screening is not considered an exclusion. Participants are encouraged to keep vaccinations up to date prior to the first dose of IMP. - Lack of clinical response to plasmapheresis / plasma exchange (PLEX). - Positive serological test at screening for active viral infection with any of the following conditions: 1) Hepatitis B virus (HBV) indicating acute or chronic infection unless associated with a negative HBV DNA test, 2) Hepatitis C virus (HCV) based on an HCV antibody assay unless associated with a negative HCV RNA test, 3) HIV based on a test result associated with either an AIDS-defining condition or a CD4 count below 200 cells / mm3 or not adequately treated with antiretroviral therapy. - Any of the following prior therapies or procedures: 1) Treatment within 2 weeks prior to screening: topical corticosteroids or topical immunomodulators (e.g., tacrolimus) for IIM-associated rash, 2) Treatment within 4 weeks prior to screening: local corticosteroid injections (intra-articular, bursal, and tendon sheath injections), anakinra, etanercept, Janus kinase (JAK) inhibitors, intramuscular or IV corticosteroids, PLEX, immunoadsorption, 3) Treatment within 8 weeks prior to screening: SC or intramuscular corticosteroid precursors, 4) Treatment within 12 weeks prior to screening: IVIg, SCIg, tocilizumab, abatacept, infliximab, adalimumab, golimumab, certolizumab, ustekinumab, 5) Treatment within 12 weeks prior to screening: 5) Use of investigational nonbiologic agents within 12 weeks or 5 half-lives (whichever is longer) prior to screening, unless a drug washout is specified in the protocol; 6) Use of a nonbiologic investigational agent within 12 weeks or 5 half-lives (whichever is longer) prior to screening, unless a drug washout is specified in the protocol; 7) Use of biologic therapy and / or monoclonal antibodies (including investigational biologic agents) within 24 weeks or 5 half-lives (whichever is longer) prior to screening, unless a drug washout is specified in the protocol; 8) Treatment with OCS doses >20 mg of prednisone or dose equivalent; 9) Treatment with more than one immunosuppressant, more than one antimalarial, or a combination of an immunosuppressant and an antimalarial. - Participant has previously participated in an efgartigimod clinical study and received at least one dose of IMP. - Participant is concurrently participating in any other clinical study, including non-interventional studies. - Participant has IgG less than 4 g / L at screening. - Participant has a current or medical history (i.e., within 12 months of screening) of alcohol, drug, or substance abuse. - Participant is pregnant or breastfeeding, or is planning to become pregnant during the study. Participant must have severe renal impairment (estimated glomerular filtration rate < 30 mL / min / 1.73 m) at screening 2 ). - Participant is institutionalized by court or other government order or is in a dependent relationship with the sponsor or investigator.

[0380] C. IMP(s) and combination therapy An investigational medicinal product (IMP) is defined as an investigational intervention(s), marketed product(s), placebo, or medical device(s) intended to be administered to study participants according to a study protocol. Administered IMP(s) [Table 6]

[0381] Any medications or vaccines (including over-the-counter or prescription drugs, recreational drugs, vitamins, and / or herbal supplements [including Chinese Traditional Medicine]) that participants are receiving at screening or during the study, or other specified category of purpose, must be recorded and include the following information: 1) reason for use, 2) dates of administration, including start and end dates, 3) dosage information, including dose and frequency.

[0382] Participants must receive background treatment for IIM and follow the requirements listed. Acceptable background treatment for IIM includes any of the following: 1) oral corticosteroids (OCS), 2) one antimalarial (hydroxychloroquine, quinacrine, or chloroquine), 3) one of the following immunosuppressants - methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mizoribine (Japan only).

[0383] Participants must be taking at least one of these specified background treatments and may receive a combination of OCS and up to one antimalarial or OCS and up to one immunosuppressant. Combinations of antimalarials and immunosuppressant drugs are not permitted. Administration of more than one drug with immunosuppressant properties, including Chinese traditional medicines, is prohibited. If a participant is receiving Chinese traditional medicine to discuss any possible immunosuppressant properties.

[0384] Ongoing physical therapy or exercise programs should follow the guidelines outlined.

[0385] Concurrent use of topical corticosteroid therapy for IIM-related rashes is not permitted. Topical treatments for non-IIM conditions in the participant's medical history are permitted at stable doses within 2 weeks of screening and throughout the study. Topical treatments to treat non-IIM-related TEAEs are also permitted.

[0386] Intramuscular or IV corticosteroids are permitted for the treatment of non-IIM-related TEAEs if the requirements for corticosteroids are met. However, participants who require intramuscular or IV corticosteroids during screening will be considered as having failed screening.

[0387] Local corticosteroid injections will be permitted to treat non-IIM-related TEAEs (e.g., local tendon, joint, bursa inflammation). However, participants who require local corticosteroid injections during screening will be considered as having failed screening.

[0388] Statins are permitted. It is recommended that statin type and dose be maintained consistently from screening to the end of the treatment period. However, dose modifications are permitted at the investigator's discretion.

[0389] Analgesics and nonsteroidal anti-inflammatory drugs will be permitted as needed based on the investigator's judgment.

[0390] Vaccines are allowed during the study, except for live or live attenuated vaccines. Vaccines must be recorded as concomitant medications. Other types of vaccines are allowed during the study at the investigator's discretion.

[0391] Corticosteroid rescue is defined as an increase in OCS dose (e.g., steroid burst) above the participant's baseline dose. Guidance on rescue treatment is provided below.

[0392] Background IIM Treatment Immunosuppressants or antimalarials may be administered at stable doses for a minimum of 12 weeks prior to screening, and for a minimum of 8 weeks prior to screening, thereafter until baseline.

[0393] Participants who discontinued treatment with immunosuppressants (except leflunomide) or antimalarials were eligible if their last dose was >8 weeks prior to screening.

[0394] Participants who discontinued treatment with leflunomide were eligible if their last dose was more than 12 weeks prior to screening, unless leflunomide washout treatment was used, in which case participants were eligible if they completed washout treatment more than 4 weeks prior to screening.

[0395] The dose regimen should remain stable from baseline to the end of the treatment period, but may be reduced due to toxicity or to optimize management of AEs such as infection. Toxicity / events must be confirmed as recorded AEs. Dose may be returned to baseline levels once toxicity / events have resolved and are clinically indicated.

[0396] OCS (up to 20 mg prednisone or dose equivalent) may be initiated more than 8 weeks prior to screening and must be on a stable dose through baseline for a minimum of 4 weeks prior to screening. Participants who discontinued treatment with OCS prior to enrollment are eligible if their last dose was more than 4 weeks prior to screening.

[0397] All corticosteroid doses are expressed in terms of equivalent prednisone doses.

[0398] Increasing the dose above the baseline dose is defined as a steroid burst. The increased dose should not be more than 20 mg above the participant's baseline dose. The following section describes the conditions under which a steroid burst is permitted.

[0399] If a steroid burst is administered because of an exacerbation of IIM disease, the following schedule is recommended: maximum dose (no more than 20 mg above the baseline dose) for 3 days, then reduce the dose by up to 5 mg every 2 to 3 days.

[0400] Disease Worsening Criteria: Disease worsening is defined as the occurrence of any of the following (compared to baseline): Worsening of MDGA ≥ 2 cm and MMT8 ≥ 20% on VAS; Worsening of global extramuscular activity ≥ 2 cm on VAS with MDAAT of 10 cm; Worsening of any three of the six IMACS CSMs ≥ 30%.

[0401] Worsening of IIMs must be recorded in the worsening report. TEAEs not related to IIMs must be described as AEs.

[0402] Phase 2:

[0403] Through Week 12: If possible, dose should be maintained stable based on participant's condition. Steroid bursts are permitted if the participant meets IIM disease worsening treatments (i.e., rescue treatment) above or if needed to treat a TEAE not related to IIM. Dose must be reduced to the participant's baseline dose within 14 days of the increase or within Visit 4, whichever occurs first. Steroid bursts beginning less than 14 days prior to Visit 4 must not be extended beyond Visit 4. A single steroid burst is permitted only if there is an imminent risk to the participant's safety, as determined by the investigator.

[0404] After Weeks 12 through 24: Dose must remain stable from Visit 4 through Visit 7. Dose escalation will only be permitted if there is an imminent risk to the participant's safety, as judged by the investigator.

[0405] Phase 3:

[0406] Through Week 40: Steroid bursts are permitted for IIM exacerbations (see above) and non-IIM related TEAEs. Up to two steroid bursts are permitted through Visit 11, but only one for IIM exacerbations. Dose must be reduced to the participant's baseline dose within 14 days of the increase or within Visit 11, whichever occurs first. Steroid bursts beginning less than 14 days prior to Visit 11 must not be extended beyond Visit 11.

[0407] After Weeks 40 through 52: Participant's dose must remain stable from Visit 11 through Visit 14. Dose escalation will only be permitted if there is an imminent risk to the participant's safety, as determined by the investigator.

[0408] OCS Tapering:

[0409] Phase 2:

[0410] Participants' OCS dose tapers are not permitted unless necessary to reduce toxicity or optimize management of AEs. Steroid toxicity or AEs must be recorded as AEs. Dose may be returned to baseline levels if toxicity or AEs resolve and if clinically indicated.

[0411] Phase 3:

[0412] Through Week 16: Participants' OCS dose tapers are not permitted unless necessary to reduce toxicity or optimize management of AEs. Steroid toxicity or AEs must be recorded as AEs. Dose may be returned to baseline levels if toxicity or AEs resolve and as clinically indicated.

[0413] After Weeks 16 through 40: OCS tapering should begin at Visit 5 and continue through Visit 14 for participants receiving more than 5 mg of corticosteroids, unless any of the disease worsening criteria are met. In this case, tapering may be delayed until the participant no longer meets these criteria. Tapering will be based on the participant's baseline dose and prednisone equivalent if the participant is receiving other OCS. After the first reduction, participants will decrease their OCS by 2.5 mg every 4 weeks. The first OCS tapering dose may be a dose reduction of less than 2.5 mg. For a baseline dose of 18-20 mg, the first reduced dose will be 17.5 mg. For a baseline dose of 16-17.5 mg, the first reduced dose will be 15 mg. For a baseline dose of 13-15 mg, the first reduced dose will be 12.5 mg. For a baseline dose of 11-12.5 mg, the first reduced dose will be 10 mg. For a baseline dose of 8-9 mg, the first reduced dose will be 7.5 mg. For a starting dose of 6-7 mg, the first reduced dose will be 5 mg. Tapering is not required for participants receiving 5 mg or less of OCS. Tapering may continue if safety or tolerability issues abate or if reduction is otherwise clinically indicated.

[0414] Participants with increasing IIM disease activity upon tapering attempt may reverse tapering by one step or less, based on the investigator's judgment. Reversal of tapering by more than one step is recommended to reverse tapering by the minimum number of steps necessary to reduce IIM disease activity. Reversal of tapering to a participant's baseline OCS dose is not considered rescue treatment.

[0415] After Weeks 40 through 52: Participants' OCS dose must remain stable from Visit 11 through Visit 14. Reductions in OCS dose after Visit 11 are permitted only to reduce toxicity or optimize management of AEs. Steroid toxicity or AEs must be documented as AEs. Dose may be returned to the 40-week dose if toxicity or AEs have resolved and if clinically indicated.

[0416] Prohibited Substances Use of cyclophosphamide, any immunomodulatory biologic, JAK inhibitors, immunoglobulin therapy, PLEX, any other experimental / investigational IMP, or live or live attenuated vaccines is not permitted from pre-enrollment through the respective washout periods until Visit 7 in the Phase 2 phase, Visit 14 in the Phase 3 phase, or the IMP discontinuation visit for participants who permanently discontinue the IMP. Participants using any of these prohibited therapies will be permanently discontinued from the IMP. These restrictions do not apply to biologics that do not have an immunomodulatory effect (e.g., insulin). If a participant's condition mandates treatment with any prohibited substance based on the investigator's judgment, the IMP must be permanently discontinued before the prohibited substance is administered. [Table 7] TIFF2025508766000008.tif247170TIFF2025508766000009.tif248170TIFF20255087660 00010.tif248170TIFF2025508766000011.tif246170TIFF2025508766000012.tif248170 [Table 8] TIFF2025508766000014.tif246170TIFF2025508766000015.tif248170TIFF2025508766000016.tif248170 TIFF2025508766000017.tif244170TIFF2025508766000018.tif249170TIFF2025508766000019.tif247170

[0417] TIS and CSM TIS will assess minimal, moderate, and substantial clinical response and will be graded using ACR / EULAR criteria.

[0418] The ACR / EULAR criteria calculate the TIS using six CSMs: MDGA, PGA, MMT8, HAQ-DI, muscle enzymes, and extramuscular global assessment (assessed by the Myositis Disease Activity Assessment Tool [MDAAT]).

[0419] The absolute percentage change from baseline in each measure with various weights is combined to obtain the TIS on a scale of 0 to 100. Higher scores indicate greater improvement. Improvement is defined by the following increases in the TIS: minimal improvement - at least 20 points, moderate improvement - at least 40 points, and significant improvement - at least 60 points.

[0420] MDGA The MDGA is a tool that measures a physician's global assessment of a participant's overall disease activity, defined as potentially reversible pathology or physiology resulting from IIM. Physicians rate disease activity on the MDGA using a 10 cm VAS.

[0421] Global disease activity is assessed by drawing vertical marks on the VAS 10 cm from the left end of the line (no evidence of disease activity), the midpoint of the line (moderate disease activity), and the right end of the line (very active or severe disease activity).

[0422] No data on the MDGA Likert scale will be collected in this study.

[0423] PGA The PGA is a tool that measures a patient's global assessment of overall disease activity at the time of assessment using a 10-cm VAS.

[0424] Participants rate global disease activity by drawing a vertical mark on a 10 cm VAS from the left end of the line (no evidence of disease activity) to the right end of the line (very active or severe disease activity).

[0425] MMT8 MMT8 is a physician-administered assessment of muscle strength in a set of eight specified muscles tested bilaterally (proximal muscles [deltoid, biceps, gluteus maximus, gluteus medius, and quadriceps], and distal muscles [wrist extensors and ankle dorsiflexors], potential score 0-140) and axially (cervical flexors, potential score 0-10). MMT8 is scored according to the Kendall scale. The highest potential MMT8 total score is 150. All 15 MMT8 muscle groups must be assessed at screening to determine eligibility. If none of the MMT8 muscle groups are assessable at screening, the participant will not be considered eligible. The following muscles (in addition to those tested in MMT8) should be assessed for weakness at screening: wrist flexors, finger flexors (flexor digitorum profundus, flexor pollicis longus), and extensor digitorum.

[0426] HAQ-DI The HAQ-DI is recommended by IMACS as a CSM in treatment studies to assess physical function and report myositis disease activity.

[0427] Participants rate their usual abilities within the past week in eight categories: dressing and grooming, standing, walking, reaching, eating, hygiene, grasping, and activity. Each category has two to three questions that participants score using a four-point scale ranging from 0 (no difficulty) to 3 (cannot do). Scores may be adjusted based on participants' answers to separate questions about the need for assistive devices and equipment, or help from others.

[0428] Muscle Enzymes Muscle-related enzymes include CK, transaminases (ALT, AST), LDH, and aldolase. These enzymes will be measured using validated methods from blood draws as shown in Tables 2 and 3. The actual date and time of blood sample collection will be collected and included in the central laboratory data transfer.

[0429] MDAAT The MDAAT is a composite tool that includes MYOACT, a serial physician assessment of disease activity in various organ systems modified from the Vasculitis Activity Index, and MITAX, modified from the British Isles Lupus Assessment Group approach to assessing disease activity in lupus.

[0430] Among the MYOACT components of the MDAAT assessment, the Extramuscular Global Assessment is a CSM of the TIS and is a tool used by physicians for the global assessment of disease activity in all extramuscular organ systems. This assessment specifically excludes muscle disease activity. Physicians use a 10 cm VAS to assess the participant's overall disease activity in all extramuscular systems within the past 4 weeks caused by active IIM disease.

[0431] The MITAX component of the MDAAT assesses disease activity in various organ systems by rating 26 clinical features within the past 4 weeks caused by active disease using a 5-point scale: 0 = absent in the past 4 weeks, 1 = improved, 2 = same, 3 = worse, 4 = new.

[0432] PGI-S and PGI-C The PGI-S and PGI-C are simple, valid, participant-rated, single-item global measures of these conditions.

[0433] The PGI-S asks participants to rate the severity of their disease symptoms over the past seven days on a four-point Likert scale, with scores ranging from "no symptoms" to "severe."

[0434] The PGI-C asks participants to rate how much their overall status has changed since the start of the study on a 7-point Likert scale ranging from "much better" to "much worse."

[0435] CGI-S and CGI-C The CGI-S and CGI-C are simple, valid, physician-rated, single-item global measures of a participant's illness.

[0436] The CGI-S asks clinicians to rate the severity of participants' illness on a four-point Likert scale, with scores ranging from "inactive" to "severe."

[0437] The CGI-C asks doctors to rate how much a participant's overall illness has changed since the start of the study on a seven-point Likert scale, with scores ranging from "much better" to "much worse."

[0438] FI-3 The FI-3 is a validated method for assessing functional impairment (i.e., muscle endurance and stamina) in patients with DM or PM. Participants attempt to perform tasks involving three different muscle groups: head lift (neck flexion), shoulder flexion, and hip flexion.

[0439] The pace of movement for each task will be standardized using a metronome (40 beats / min). Participants will attempt to perform up to 60 hip and shoulder flexion repetitions within 3 min and up to 30 head flexion repetitions within 1.5 min. After performing each task, participants will rate perceived muscle exertion on the Borg CR-10 scale from 0 (no exertion) to 10 (maximum exertion).

[0440] PROMIS evaluation PROMIS is a publicly available system of reliable and accurate measurements of patient-reported health status for physical, mental, and social well-being. PROMIS instruments measure concepts including pain, fatigue, and physical function.

[0441] The PROMIS Fatigue (Short Form 7a) instrument assesses the impact and experience of fatigue over the past 7 days. This validated 7-question scale has 5 response options and scores range from 1 to 5. Scores are converted to T-scores, with higher scores indicating higher levels of fatigue. A decrease in score (negative change from baseline) indicates improvement in fatigue.

[0442] The PROMIS Pain Interference (Short Form 6a) instrument measures self-reported outcomes of pain across aspects of life, including social, cognitive, emotional, physical, and recreational activities during the past 7 days. This validated 6-question scale has 5 response options and scores range from 1 to 5. Scores are converted to T-scores, with higher scores indicating greater pain interference. A decrease in score (negative change from baseline) indicates improvement in pain interference.

[0443] The PROMIS Physical Function (Short Form 8b) instrument measures self-reported capacity rather than actual performance of physical activity. A single physical functional capacity score is derived from the Short Form. This validated eight-question scale has five response options and scores range from 1 to 5. Scores are converted to T-scores, with higher scores indicating better self-reported capacity in physical functioning. An increase in score (positive change from baseline) indicates improvement in self-reported physical functioning.

[0444] pain NRS Participants were asked to record a score (0 to 10) for the worst pain they had experienced within the past 7 days.

[0445] Fatigue NRS Participants were asked to record a score (0–10) for the worst physical fatigue they had experienced within the past seven days.

[0446] SF-36v2 The SF-36v2 is a 36-item scale constructed to investigate health-related quality of life in eight domains: 1) limitations in physical activity caused by health problems, 2) limitations in social activities caused by physical or emotional problems, 3) limitations in usual role activities caused by physical health problems, 4) bodily pain, 5) overall mental health (psychological distress and well-being), 6) limitations in usual role activities caused by emotional problems, 7) vitality (energy and fatigue), and 8) overall health perception.

[0447] EQ-5D-5L The EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a generic measure of health status for clinical and economic evaluations.

[0448] The descriptive system includes five items: 1) mobility, 2) self-care, 3) usual activities, 4) pain / discomfort, and 5) anxiety / depression.

[0449] Each item has five levels: 1) no problem, 2) mild problem, 3) moderate problem, 4) severe problem, and 5) extreme problem.

[0450] Participants will be asked to indicate their health status by checking a box (or putting a cross) against the most appropriate statement in each of the five items. This decision will result in a single digit number representing the level chosen for that item. The numbers for the five items will be compiled into a five digit number representing the respondent's health status. A unique health status will be defined by combining one level from each of the five items. In this way, a total of 3125 possible health states can be defined. Each status is expressed in terms of a five digit code. For example, the status 11111 indicates no problems in any of the five items, while the status 12345 indicates no problems with mobility, slight problems with washing or dressing, moderate problems with performing normal activities, severe pain or discomfort, and extreme anxiety or depression.

[0451] The VAS is included in the EQ-5D-5L, where participants are asked to mark their health status on the day the interview takes place from 0 (the worst health you can imagine) to 100 (the best health you can imagine).

[0452] m30 STS test The m30 STS test measures proximal muscle weakness. Participants will be seated in a standard chair with armrests and will be instructed to stand up and sit down again for 30 seconds. If necessary, participants can use their hands and arms to assist them in standing up. The number of sit-to-stand repetitions will be recorded.

[0453] Monitor actigraphy Participants will be instructed to wear an actigraph (physical activity monitor) at the times specified in the SoA, which will record step count, cadence, vector magnitude, and time spent in different levels of daily activity (light, moderate-vigorous, and sedentary).

[0454] Abbreviated portable dynamometry Portable dynamometry measures the peak isometric force generated from muscle groups and will be used to quantify muscle strength in patients with IIM. Muscle strength will be assessed by portable dynamometry on both sides of the deltoid and iliopsoas muscles using the provided dynamometer and following the methods specified in the study manual.

[0455] CDASI (only for participants with DM) The CDASI is a skin-specific outcome measure used to assess disease in patients with DM. Disease in 15 different anatomical locations is assessed using three activity measures (erythema, scaling, erosion / ulceration) and two damage measures (poikiloderma, calcification). The three activity measures in 15 anatomical locations can add up to 90 points. The hands, periungual Gottron papules, and alopecia can add up to 10 points. The two damage measures in 15 anatomical locations can add up to 30 points for the Gottron hands and an additional 2 points for the alopecia. The CDASI also assesses the presence and severity of Gottron papules, periungual changes, and alopecia. The resulting activity and damage scores range from 0 to 100 and 0 to 32, respectively. Higher scores indicate greater disease severity.

[0456] Pruritus NRS (participants with DM only) DM pruritus symptoms will be assessed by participants using the Pruritus NRS, which involves recording the average and worst scores (0-10) for the itch they experienced in the past 24 hours.

[0457] Skindex-16 (only for participants with DM) The Skindex-16 is a one-page survey that assesses how symptoms, feelings, and functioning from skin symptoms of DM affect participants' quality of life. Using a Likert scale from 0 (never) to 6 (always), participants rate the frequency of each skin disease effect in the previous week. The Skindex-16 provides a single score and a mean score for each domain (symptoms, feelings, and functioning).

[0458] MDI The MDI is a tool used in physician assessment of the extent and severity of disease damage in 11 organ systems. In this study, only the muscle damage VAS will be used, and the severity of damage is measured by the physician's global assessment of disease damage to the muscular system using a 10 cm VAS.

[0459] Damage is defined as a persistent / permanent change in anatomy, physiology, pathology, or function that occurs after a diagnosis of myositis and is believed to be present for at least 6 months. Damage may be the result of previous active disease (causing scarring, fibrosis, and atrophy), complications of therapy, coexisting conditions, or other events. Part of the damage of the disease is the chronicity of the disease. The damage features must be confirmed by clinical evaluation and present for at least 6 months (or the pathology leading to the features must be present for at least 6 months) despite previous immunosuppressive or other therapy, including exercise and rehabilitation. Examples of muscle damage include, but are not limited to, muscle atrophy (assessed by loss of muscle mass on clinical examination and / or by radiographic methods), muscle weakness not attributable to active muscle disease, and muscle dysfunction (e.g., loss of aerobic exercise tolerance not attributable to other factors).

[0460] Muscle biopsy Participants who require a muscle biopsy diagnosis for inclusion in the study will submit a previous muscle biopsy slide for review by the Biopsy Adjudication Committee. Full details of this process are described in the Biopsy Adjudication Charter.

[0461] If a participant requiring a muscle biopsy does not have previous biopsy data available, the participant will not be considered eligible for enrollment. If a biopsy is performed after a screening failure within the participant's routine medical course, that biopsy may be used if the participant is rescreened.

[0462] C-GTI (Phase 3 only) The C-GTI serves as a primary instrument to capture possible toxicities caused by glucocorticoid exposure and allows monitoring of the long-term tolerability of glucocorticoids during chronic use. The C-GTI has nine functional domains: body mass index, glucose regulation, BP, lipid metabolism, bone mineral density, muscle strength, skin toxicity, neuropsychiatric effects, and infection. Each domain contains several weighted items corresponding to various degrees of glucocorticoid toxicity. In this study, the bone mineral density domain will not be evaluated.

[0463] Two analytical scores are generated from the weighted C-GTI items: the CWS and the AIS. The CWS is designed to assess cumulative glucocorticoid toxicity, and the AIS can be used to evaluate whether a new therapy is effective at reducing glucocorticoid toxicity over time. Both the CWS and the AIS provide complementary information about the ability of an investigational agent to reduce overall glucocorticoid toxicity.

[0464] E. Pharmacokinetics Blood samples for PK analysis will be collected for measurement of serum concentrations of efgartigimod as specified in Tables S2 and S3. Sampling should be performed pre-dose, preferably within 2 hours before IMP is administered. During unscheduled visits, blood samples for PK will be collected only if IMP is administered.

[0465] Serum efgartigimod concentrations will be determined using a validated assay.

[0466] In the Phase 2 phase of the study only, optional additional PK samples will be collected at selected investigational sites on Day 3 (± 1 day; opt-in visit) until at least 32 participants have these additional PK samples. This blood sampling should preferably be performed at the site, although if necessary, samples may be collected at the participant's home by qualified personnel.

[0467] No intervention concentration information that could unblind the study will be reported to the study sites or blinded personnel.

[0468] F. Pharmacodynamics Blood samples will be collected for determination of total IgG serum levels as described in Tables S2 and S3. Total IgG will be determined using a validated assay.

[0469] Screening will involve measuring total IgG serum levels to assess eligibility.

[0470] At baseline and all post-baseline PD assessment time points, sample collection will be performed pre-dose.

[0471] Total IgG concentrations will be quantified in a central laboratory and results will not be reported to the study site or other study personnel in order to maintain study blinding.

[0472] PD blood samples collected at the screening visit may be used for methodology validation and / or future research purposes. Such use of these samples will be allowed only after obtaining informed consent from participants.

[0473] G. Genetics The assessment will include measurement of the IFN signature, a normalized score calculated from the set of transcripts systemically induced by IFN (IFN score). This assessment will be mandatory unless classified as a genetic test by local regulations, in which case this assessment will be optional and will only be assessed if the participant consents.

[0474] H. Biomarkers Blood samples will be collected and serum will be aliquoted for biomarker measurements according to Tables S2 and S3. Full details of measurements and methods are provided in the laboratory manual provided separately to the facility.

[0475] MSA and MAA Blood samples will be collected and serum will be aliquoted for measurement of MSA and MAA. Samples will be collected according to the schedules listed in Tables S2 and S3. Separate samples will be collected for MSA and MAA as follows:

[0476] Screening samples for the presence of specific MSAs used for eligibility and classification of participants' IIM subtypes.

[0477] Measurement of MSA / MAA titers. The MSA / MAA panel may include, but is not limited to: MSA: anti-SRP, -HMGCR, -Mi-2, -TIF1, -SAE, -NXP, -MDA5, -Jo-1, -PL-7, -PL-12, -EJ, -OJ, PM / Scl-75, and Ku; MAA: snRNP, -Ro52(SSA), -Ro / 60(SSA), -La(SSB).

[0478] Optional baseline samples for research in MSA assay testing and methods. These samples may be used for further MSA assay testing and research in the IIM population only. Thus, blood samples may be collected for future exploratory studies, if local regulations and IRB / IEC permit.

[0479] Other exploratory biomarkers Samples will be collected for the following measurements as specified in Tables 2 and 3:

[0480] This may include, but is not limited to, immunophenotyping of PBMCs, including assessment of the percentage of CD19+ B cells within the CD45+ population, and assessment of myositis-antigen specificity.

[0481] Assessment of IFN concentrations, including but not limited to IFN-alpha and IFN-beta protein levels.

[0482] Assessment of IFN gene expression score (regulation of IFN-regulated gene expression) by nanostring technology, including but not limited to mRNA quantification of the following six interferon stimulated genes (ISGs): interferon alpha-inducible protein 27 (IFI27), interferon-inducible protein 44 (IFI44L), interferon-inducible protein with tetratricopeptide repeats 1 (IFIT1), ISG15 ubiquitin-like modifier (ISG15), radical S-adenosylmethionine domain containing 2 (RSAD2), and sialic acid-binding Ig-like lectin 1 (SIGLEC1). In addition, three housekeeping genes will be evaluated: actin beta (ACTB), hypoxanthine phosphoribosyltransferase (HPRT1), and RNA polymerase II subunit A (POLR2A). Testing of this sample is mandatory unless classified as a genetic test by local regulations. If considered a genetic test, this evaluation is optional.

[0483] Serological markers of complement activation, including but not limited to C3, C4, and / or their cleavage products (C3b / c and C4b / c).

[0484] I. Immunogenicity Assessment Blood samples will be collected to assess serum levels of ADA to efgaltigimod and plasma levels of antibodies to rHuPH20 from all participants as listed in Tables S2 and S3. Full details of the measurements and methods are described in the laboratory manual provided separately to the sites. Immunogenicity samples taken at screening will be used for validation purposes only.

[0485] All samples will be analyzed in a three-tiered approach using validated immunogenicity methods. First, all samples will be evaluated in a screening assay (Tier 1) and scored positive or negative. Second, screened positive samples will be evaluated in a confirmatory assay (Tier 2) to assess the specificity of the immunogenic response. Samples will be scored as confirmed positive or confirmed negative. Samples confirmed as positive in Tier 2 will be further analyzed in a titration assay to characterize the magnitude of the antibody response and a neutralizing antibody assay (Tier 3) to assess the antibodies for neutralizing activity. J. Objectives and Evaluation Items [Table 9] TIFF2025508766000021.tif239170TIFF2025508766000022.tif58170

[0486] The present invention is not limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims.

Claims

1. 1. A method of treating myositis in a subject in need thereof, said method comprising administering to said subject an effective amount of a human neonatal Fc receptor (FcRn) antagonist.

2. The method of claim 1 , wherein the FcRn antagonist comprises two, three, or four FcRn binding regions.

3. The method of claim 1 or 2, wherein the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof.

4. The method of claim 3, wherein the variant Fc region, or FcRn-binding fragment thereof, binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region.

5. 5. The method of claim 3 or 4, wherein the variant Fc region, or FcRn-binding fragment thereof, binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

6. 6. The method of any one of claims 3 to 5, wherein the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or a heterodimer.

7. 7. The method of claim 6, wherein the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively.

8. 8. The method of claim 6 or 7, wherein the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

9. 9. The method of any one of claims 6 to 8, wherein the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:

3.

10. 10. The method of any one of claims 6 to 9, wherein the first Fc domain and the second Fc domain comprise amino acid sequences independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:

3.

11. The method of any one of claims 1 to 10, wherein the FcRn antagonist is efgartigimod.

12. The method of claim 1 , wherein the FcRn antagonist is an anti-FcRn antibody.

13. 13. The method of any one of claims 1 to 12, wherein the FcRn antagonist is administered to the subject at a fixed dose of 20 mg to 20,000 mg, or at a dose of 0.2 mg / kg to 200 mg / kg.

14. 14. The method of any one of claims 1-13, wherein the FcRn antagonist is administered subcutaneously once every week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

15. 15. The method of claim 14, wherein the FcRn antagonist is administered subcutaneously at a fixed dose of 200 mg to 20,000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

16. 16. The method of claim 14 or 15, wherein the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

17. 17. The method of claim 16, wherein the FcRn antagonist is initially administered subcutaneously in a fixed dose of about 1000 mg twice on the same day.

18. 12. The method of claim 11, wherein the efgartigimod is administered subcutaneously once weekly at a fixed dose of 800-1200 mg.

19. 12. The method of claim 11, wherein the efgartigimod is administered subcutaneously once weekly at a fixed dose of about 1000 mg.

20. 12. The method of claim 11, wherein the efgartigimod is administered subcutaneously once weekly at a fixed dose of 1000 mg.

21. The method of any one of claims 14 to 20, wherein the FcRn antagonist is co-formulated with hyaluronidase and administered subcutaneously.

22. 22. The method of claim 21, wherein the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

23. 23. The method of claim 22, wherein the rHuPH20 is administered at about 11,000 U once a week.

24. The method of any one of claims 1 to 13, wherein the FcRn antagonist is administered intravenously once every week or once every two weeks.

25. 25. The method of claim 24, wherein the FcRn antagonist is administered intravenously once every week or once every two weeks at a dose of 2 mg / kg to 200 mg / kg.

26. 26. The method of claim 24 or 25, wherein the FcRn antagonist is administered intravenously once every week or once every two weeks at a dose of 3 mg / kg to 60 mg / kg.

27. 27. The method of any one of claims 24 to 26, wherein the FcRn antagonist is administered intravenously at a dose of 10 mg / kg once every week or once every two weeks.

28. 27. The method of any one of claims 24 to 26, wherein the FcRn antagonist is administered intravenously at a dose of 25 mg / kg once every week or once every two weeks.

29. The method of any one of claims 1 to 28, wherein the FcRn antagonist is administered for up to 52 weeks.

30. The method of any one of claims 1 to 29, wherein the FcRn antagonist is administered for up to 24 weeks.

31. The method of any one of claims 1 to 29, wherein the FcRn antagonist is administered for at least 24 weeks.

32. The method of any one of claims 1 to 28, wherein the FcRn antagonist is administered for at least 52 weeks.

33. 33. The method of any one of claims 1 to 32, further comprising administering to the subject a dose of a corticosteroid.

34. 34. The method of claim 33, wherein the dose of corticosteroid is reduced after 16 weeks of treatment with the FcRn antagonist.

35. 35. The method of claim 33 or 34, wherein the corticosteroid is prednisone.

36. 36. The method of claim 35, wherein the dose of prednisone is decreased after 16 weeks of treatment with the FcRn antagonist if the dose of prednisone is administered to the subject at greater than 5 mg per day prior to the dose of prednisone being decreased.

37. 37. The method of claim 36, wherein after 16 weeks of treatment with the FcRn antagonist, the daily dose of prednisone is reduced by 2.5 mg and the reduced dose is maintained for 4 weeks.

38. 37. The method of claim 36, wherein after 16 weeks of treatment with the FcRn antagonist, the daily dose of prednisone is reduced by 2.5 mg every 4 weeks for one or more 4-week periods.

39. 39. The method of any one of claims 35-38, wherein the prednisone is administered at 20 mg or less per day.

40. 40. The method of any one of claims 1 to 39, wherein the myositis is selected from the group consisting of immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), juvenile dermatomyositis (JDM), polymyositis (PM), and antisynthetase syndrome (ASyS).

41. The method of any one of claims 1 to 40, wherein the subject is diagnosed with idiopathic inflammatory myopathy (IIM).

42. 42. The method of claim 41, wherein the IIM is selected from the group consisting of IMNM, DM, JDM, PM, and ASyS.

43. The method of any one of claims 1 to 42, wherein the myositis is IMNM.

44. The method of any one of claims 1 to 42, wherein the myositis is DM or JDM.

45. The method of any one of claims 1 to 44, wherein the subject has an active DM skin rash.

46. 46. ​​The method of claim 45, wherein the active DM skin rash is selected from the group consisting of Gottron papules, Gottron signs, and heliotrope rash.

47. The method of any one of claims 1 to 42, wherein the myositis is PM or ASyS.

48. 48. The method of any one of claims 1 to 47, wherein the subject has detectable serum levels of myositis-associated antibodies (MAA) or myositis-specific antibodies (MSA).

49. The method of claim 48, wherein the MSA is an anti-aminoacyl-tRNA synthetase antibody.

50. 50. The method of claim 49, wherein the anti-aminoacyl-tRNA synthetase antibody is selected from the group consisting of anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ antibodies.

51. 49. The method of claim 48, wherein the MSA is selected from the group consisting of anti-SRP, anti-HMGCR, anti-Mi-2, anti-TIF1, anti-SAE, anti-NXP, and anti-MDA5 antibodies.

52. 49. The method of claim 48, wherein the MAA is selected from the group consisting of anti-PM / Scl75, anti-Ku, anti-snRNP, anti-Ro52 (SSA), anti-Ro / 60 (SSA), and anti-La (SSB) antibodies.

53. The method of any one of claims 48 to 52, wherein the subject exhibits a reduction in serum levels of the MAA or MSA following administration of an anti-FcRn antagonist.

54. 54. The method of claim 53, wherein the reduction in the serum level of the MAA or MSA following administration of the anti-FcRn antagonist is at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the subject's serum level of the MAA or MSA before administration of the anti-FcRn antagonist.

55. 55. The method of claim 53 or 54, wherein the serum levels of the MAA or MSA are undetectable after administration of the FcRn antagonist.

56. 56. The method of any one of claims 1 to 55, wherein the subject exhibits a TIS of at least 20 points.

57. 57. The method of claim 56, wherein the subject exhibits a TIS of at least 20 points within 12 weeks.

58. 58. The method of claim 56 or 57, wherein the subject exhibits a TIS of at least 20 points within 6 weeks.

59. 56. The method of any one of claims 1 to 55, wherein the subject exhibits a TIS of at least 40 points.

60. 56. The method of any one of claims 1 to 55, wherein the subject exhibits a TIS of at least 60 points.

61. 61. The method of any one of claims 1-60, wherein the subject shows at least a 20% improvement in MMT8 score.

62. 62. The method of any one of claims 1-61, wherein the subject shows at least a 30% improvement in MMT8 score.

63. 63. The method of any one of claims 1-62, wherein the subject exhibits at least a 20% reduction in Patient Global Assessment (PGA) of disease activity.

64. 64. The method of any one of claims 1-63, wherein the subject exhibits at least a 30% decrease in PGA.

65. 65. The method of any one of claims 1 to 64, further comprising measuring at least one muscle-associated enzyme in the subject, wherein a reduction in at least one muscle-associated enzyme in the subject indicates an improvement in the disease.

66. 66. The method of claim 65, wherein the at least one muscle-associated enzyme is selected from the group consisting of creatine kinase, alanine aminotransferase, aspartate aminotransaminase, lactate dehydrogenase, and aldolase.

67. 67. The method of claim 66, wherein the at least one muscle-associated enzyme is creatine kinase.

68. 13. An FcRn antagonist for use in the treatment of myositis, said treatment being carried out according to the method of any one of the preceding claims.

69. 13. An FcRn antagonist for use in the manufacture of a medicament for the treatment of myositis, wherein said treatment is carried out according to the method of any one of the preceding claims.

70. 1. A method for monitoring the effectiveness of a treatment of myositis in a subject following treatment with a first FcRn antagonist, the method comprising: a) measuring in vitro the serum level of MAA or MSA in a blood sample taken from said subject; b) comparing the serum level of the MAA or MSA to a reference value associated with myositis in the subject; The method, wherein if the serum level of the MAA or MSA in the sample is equal to or greater than the reference value, the treatment is ineffective, and if the serum level of the MAA or MSA is less than the reference value, the treatment is effective.

71. 1. A method of treating myositis in a subject receiving a first FcRn antagonist and a corticosteroid dosing regimen, the method comprising: a) administering to the subject an effective amount of a second FcRn antagonist; b) measuring in vitro the serum level of MAA or MSA in a blood sample taken from said subject; c) comparing the serum level of the MAA or MSA to a reference value associated with myositis in the subject; wherein the corticosteroid dosing regimen is maintained if the serum level of the MAA or MSA in the sample is equal to or greater than the reference value, or the corticosteroid dosing regimen is tapered if the serum level of the MAA or MSA in the sample is less than the reference value.

72. 1. A method for treating myositis in a subject, comprising: (a) administering to the subject one or more initial doses of an effective amount of a first FcRn antagonist; (b) administering to the subject one or more further doses of an effective amount of a second FcRn antagonist if the serum level of the MAA or MSA in the subject after step (a) is equal to or greater than a reference level associated with myositis in the subject, or discontinuing treatment with the first FcRn antagonist if the serum level of the MAA or MSA in the subject after step (a) is less than a reference level associated with active disease in the subject.

73. 1. A method for treating myositis in a subject, the method comprising administering to the subject an effective amount of a second FcRn antagonist; The method, wherein the myositis has recurred in the subject after prior therapy with a first FcRn antagonist, and the subject has a serum level of MAA or MSA that is equal to or greater than a reference level associated with myositis in the subject.

74. 1. A method for determining whether a subject previously treated for myositis with a first FcRn antagonist requires further treatment with a second FcRn antagonist, the method comprising: a) measuring in vitro the serum level of MAA or MSA in a blood sample taken from said subject; b) comparing the serum level of the MAA or MSA to a reference value associated with myositis in the subject; If the serum level of the MAA or MSA in the sample is equal to or greater than the reference value, the subject requires further treatment with the second FcRn antagonist.

75. 75. The method of any one of claims 70-74, wherein the subject has previously been treated with the first FcRn antagonist at a fixed dose of about 200 mg to about 20,000 mg, or at a dose of 2 mg / kg to 200 mg / kg.

76. 76. The method of claim 75, wherein the subject was previously treated with the first FcRn antagonist at a dose of about 750 mg to about 3000 mg administered subcutaneously.

77. 76. The method of claim 75, wherein the subject was previously treated with the first FcRn antagonist at a dose of about 3 mg / kg to about 60 mg / kg administered intravenously.

78. 78. The method of claims 71-77, wherein the effective amount of the second FcRn antagonist is a higher dose than previous treatment with the first FcRn antagonist.

79. 78. The method of any one of claims 71-77, wherein the effective amount of the second FcRn antagonist is a lower dose than previous treatment with the first FcRn antagonist.

80. 80. The method of any one of claims 71-79, wherein the effective amount of the second FcRn antagonist is administered in a fixed dose of about 200 mg to about 20,000 mg, or in a dose of about 2 mg / kg to about 200 mg / kg.

81. 81. The method of claim 80, wherein the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 750 mg to about 3000 mg once every week, every two weeks, every three weeks, every four weeks, or every six weeks.

82. 81. The method of claim 80, wherein the effective amount of the second FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg or about 2000 mg once every week, every two weeks, every three weeks, every four weeks, or every six weeks.

83. 83. The method of any one of claims 71-82, wherein the first FcRn antagonist and the second FcRn antagonist are each the same FcRn antagonist.

84. The method of any one of claims 71 to 82, wherein the first FcRn antagonist and the second FcRn antagonist are each a different FcRn antagonist.

85. 85. The method of claim 84, wherein the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof.

86. 85. The method of claim 84, wherein the first FcRn antagonist or the second FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof.

87. 87. The method of claim 85 or 86, wherein the variant Fc region, or FcRn-binding fragment thereof, binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region.

88. 87. The method of claim 85 or 86, wherein the variant Fc region comprises or consists of two Fc domains that form a homodimer or heterodimer.

89. 90. The method of any one of claims 83, 85, 87, or 88, wherein the FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

90. 90. The method of any one of claims 84, 86, 87, or 88, wherein the first FcRn antagonist or the second FcRn antagonist is an Fc region comprising amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

91. 90. The method of claim 89, wherein the FcRn antagonist is efgartigimod.

92. 91. The method of claim 90, wherein the first FcRn antagonist or the second FcRn antagonist is efgartigimod.

93. 90. The method of any one of claims 83, 85, 87, or 88, wherein at least one amino acid sequence of the Fc domain is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:

3.

94. 90. The method of any one of claims 84, 86, 87, or 88, wherein the amino acid sequences of both of the Fc domains are independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:

3.

95. 94. The method of claim 93, wherein the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist is efgartigimod.

96. 94. The method of claim 93, wherein the first FcRn antagonist is an anti-FcRn antibody and the second FcRn antagonist comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3.

97. 97. The method of claim 95 or 96, wherein the patient has not been previously treated with efgartigimod.

98. The method of any one of claims 71-97, wherein the subject has one or more physical symptoms of myositis after treatment with the first FcRn antagonist.

99. The method of any one of claims 71 to 98, wherein the subject has a serum level of MAA or MSA associated with a relapse of myositis.

100. 100. The method of any one of claims 71 to 99, wherein the MSA is selected from the group consisting of anti-SRP, anti-HMGCR, anti-Mi-2, anti-TIF1, anti-SAE, anti-NXP, anti-MDA5, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-OJ.

101. The method of any one of claims 71 to 100, wherein the MAA is selected from the group consisting of anti-PM / Scl75, anti-Ku, anti-snRNP, anti-Ro52 (SSA), anti-Ro / 60 (SSA), and anti-La (SSB).

102. 102. The method of any one of claims 71-101, wherein the myositis is selected from the group consisting of IMNM, DM, JDM, PM, and ASyS.

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