Anti-CD19 binding agents for the treatment and prevention of immune-mediated necrotizing myopathy

Abstract

The present disclosure relates to compositions and methods for treating diseases (e.g., myositis) in a subject in need thereof using an anti-CD19 antibody or an antigen-binding fragment thereof. For example, the present invention provides a method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or an antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 480,908, filed January 20, 2023, which is incorporated herein by reference in its entirety for all purposes.

[0002] Sequence Listing The contents of the electronic sequence listing (HOPA_064_01WO_SeqList_ST26.xml; size: 10,639 bytes; and creation date: January 4, 2024) are incorporated herein by reference in their entirety.

[0003] The present disclosure relates to compositions comprising anti-CD19 binding proteins and methods of using same in the treatment and prevention of myopathies. [Background technology]

[0004] If idiopathic inflammatory myopathy is not promptly controlled, it may lead to permanent muscle damage accompanied by muscle weakness. Currently, corticosteroids, intravenous immunoglobulin (IVIG), and other immunomodulators are used for treatment, but these drugs are also associated with side effects, including the risk of diabetes, osteoporosis, cataracts, opportunistic infections, and thrombosis. In addition, some patients cannot control their disease in a timely manner with these therapies. This, along with the burden of side effects, has created a clinical need for therapies to treat these patients.

[0005] Cluster of differentiation 19 (CD19) can be targeted for the treatment and prevention of myopathy. Accordingly, compositions and methods are provided that utilize anti-CD19 antibodies or antigen-binding fragments thereof to reduce or eliminate symptoms or diseases associated with CD19. Summary of the Invention [Means for solving the problem]

[0006] Provided is a method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8.

[0007] Provided is a method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, and the subject in need thereof is a child. In one embodiment, the pediatric subject is 16 to 18 years of age.

[0008] Provided is a method for treating immune-mediated necrotizing myopathy (IMNM), comprising the step of administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, where HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is approximately 100 mg to 1000 mg.

[0009] Provided is a method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is about 300 mg.

[0010] Provided is a method of treatment comprising administering to a pediatric subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively.

[0011] Provided is a method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of inebilizumab to a subject in need thereof, wherein the effective amount is between about 100 mg and 1000 mg.

[0012] Provided is a method of treatment comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is positive for an autoantibody selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0013] Provided is a method of treatment comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is negative for autoantibodies selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0014] In embodiments, the subject is signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl-coenzyme A reductase-antibody positive (HMGCR-Ab+), or both SRP-Ab+ and HMGCR-Ab+. In embodiments, the subject is SRP-Ab+. In embodiments, the subject is HMGCR-Ab+. In embodiments, the subject is signal recognition particle-antibody negative (SRP-Ab-), 3-hydroxy-3-methylglutaryl-coenzyme A reductase-antibody negative (HMGCR-Ab-), or both SRP-Ab- and HMGCR-Ab-. In embodiments, the subject in need thereof has previously been treated with conventional therapy. In embodiments, the conventional therapy includes corticosteroids, nonsteroidal immunosuppressants (ISTs), antibody therapy, or any combination thereof. In embodiments, the conventional therapy is a corticosteroid, and the corticosteroid is prednisone. In some embodiments, the conventional therapy is an IST selected from the group consisting of methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and any combination thereof. In some embodiments, the conventional therapy is an antibody therapy selected from the group consisting of rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab intravenous immunoglobulin (IVIg), and combinations thereof. In some embodiments, after administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, the conventional therapy is tapered. In some embodiments, tapering comprises reducing the dosage of the conventional therapy every two weeks starting at week 26. In some embodiments, the conventional therapy includes prednisone, and the prednisone is tapered by 5 mg every two weeks after administration. In some embodiments, tapering continues until at least week 12. In embodiments, the subject was determined to have at least one of SRP-Ab or HMGCR-Ab prior to administration. In embodiments, administration of the anti-CD19 antibody or antigen-binding fragment thereof is repeated. In embodiments, administration is repeated at weeks 2, 26, 52, 78, 104, 130, and 156. In embodiments, the administration, repeated administration, or both, is effective to alleviate the disease or its symptoms by week 12, 26, or 52.In an embodiment, the administration, repeat administration, or both is determined by an increase in the 2016 ACR / EULAR Total Improvement Score (TIS). Decision In embodiments, the administration, repeated administration, or both are effective to reduce the disease or symptoms thereof by 26 weeks after administration, compared to the subject's baseline score or the score of an untreated subject. In embodiments, the administration, repeated administration, or both are effective to reduce the disease or symptoms thereof by 26 weeks after administration, compared to the subject's baseline level or the level of an untreated subject. In embodiments, the reduction in the disease or symptoms thereof is determined by improvement in muscle weakness, reduction in serum CK levels, reduction in atrophy, reduction in edema, reduction in fatty tissue replacement, reduction in interstitial lung disease, reduction in B cell levels, MMT8 score, and combinations thereof. In embodiments, the subject is a human. In embodiments, the reduction in the disease is at least about 3-fold, 5-fold, 20-fold, 40-fold, 60-fold, 80-fold, or up to ... in In an embodiment, the TIS score is ≧5, 10, 20, 30, 40, 50, 60, 80, or 100. In an embodiment, a glucocorticoid, an antihistamine, an analgesic, or any combination thereof is administered prophylactically prior to administration to a subject in need thereof. In an embodiment, the subject is administered prophylactically a glucocorticoid, an antihistamine, and an analgesic. In an embodiment, the subject is administered prophylactically methylprednisolone, diphenhydramine, and acetaminophen. In an embodiment, the effective amount of the anti-CD19 antibody or antigen-binding fragment thereof is about 50 mg to 1000 mg, 100 to 800 mg, In an embodiment, the effective amount is: aboutThe effective dose is 50 mg, 100 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the effective amount is about 300 mg. In embodiments, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In embodiments, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In embodiments, the anti-CD19 antibody is a monoclonal antibody. In embodiments, the anti-CD19 antibody is defucosylated. In embodiments, the administration, repeated administration, or both, is effective to eliminate IMNM for at least about 3 months, 6 months, 1 year, or 2 years. In embodiments, the administration, repeated administration, or both, is effective to stabilize or reduce IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0015] In embodiments, administration of any of the disclosed methods comprises 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof on days 1 and 15, followed by one 300 mg injection approximately every six months thereafter.

[0016] Also provided is a method of treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, where HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is about 300 mg administered every six months, with an initial dose of 300 mg administered two weeks before the first 300 mg dose every six months. In embodiments, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), where the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In aspects, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0017] Provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM), the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8. Provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM) in a pediatric subject, the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise SEQ ID NOs: 2, 3, 4, 6, 7, and 8. In embodiments, the pediatric subject is 16-18 years old. In embodiments, the subject is signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl-coenzyme A reductase-antibody positive (HMGCR-Ab+), or both SRP-Ab+ and HMGCR-Ab+. In embodiments, the subject is SRP-Ab+. In embodiments, the subject is HMGCR-Ab+. In embodiments, the subject is signal recognition particle-antibody negative (SRP-Ab-), 3-hydroxy-3-methylglutaryl-coenzyme A reductase-antibody negative (HMGCR-Ab-), or both SRP-Ab- and HMGCR-Ab-. In one embodiment, the subject in need thereof has previously been treated with conventional therapy. In one embodiment, the conventional therapy comprises a corticosteroid, a nonsteroidal immunosuppressant (IST), an antibody therapy, or any combination thereof. In one embodiment, the conventional therapy is a corticosteroid, and the corticosteroid is prednisone. In one embodiment, the conventional therapy is an IST selected from the group consisting of methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and any combination thereof. In one embodiment, the conventional therapy is an antibody therapy selected from the group consisting of rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab intravenous immunoglobulin (IVIg), and combinations thereof. In one embodiment, after administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, the conventional therapy is tapered. In embodiments, tapering comprises reducing the dosage of the conventional therapy every two weeks starting at week 26. In embodiments, the conventional therapy includes prednisone, and the prednisone is tapered by 5 mg every two weeks after administration. In embodiments, tapering continues until at least week 12. In embodiments, the subject was determined to have at least one of SRP-Ab or HMGCR-Ab prior to administration. In embodiments, administration of the anti-CD19 antibody or antigen-binding fragment thereof is repeated. In embodiments, administration is repeated at weeks 2, 26, 52, 78, 104, 130, and 156. In embodiments, the administration, repeated administration, or both is effective in alleviating the disease or its symptoms by week 12, 26, or 52. In embodiments, the administration, repeated administration, or both is effective in alleviating the disease or its symptoms by week 12, 26, or 52. In embodiments, the administration, repeated administration, or both is effective in alleviating the disease or its symptoms by week 12, 26, or 52, as determined by an increase in the 2016 ACR / EULAR Total Improvement Score (TIS). DecisionIn embodiments, the administration, repeated administration, or both are effective to reduce the disease or symptoms thereof by 26 weeks after administration, compared to the subject's baseline score or the score of an untreated subject. In embodiments, the administration, repeated administration, or both are effective to reduce the disease or symptoms thereof by 26 weeks after administration, compared to the subject's baseline level or the level of an untreated subject. In embodiments, the reduction in the disease or symptoms thereof is determined by improvement in muscle weakness, reduction in serum CK levels, reduction in atrophy, reduction in edema, reduction in fatty tissue replacement, reduction in interstitial lung disease, reduction in B cell levels, MMT8 score, and combinations thereof. In embodiments, the subject is a human. In embodiments, the reduction in the disease is at least about 3-fold, 5-fold, 20-fold, 40-fold, 60-fold, 80-fold, or up to ... inThe TIS score is about 100 times greater. In embodiments, the TIS score is ≧5, 10, 20, 30, 40, 50, 60, 80, or 100. In embodiments, a glucocorticoid, an antihistamine, an analgesic, or any combination thereof is administered prophylactically prior to administration to a subject in need thereof. In embodiments, the subject is administered a glucocorticoid, an antihistamine, and an analgesic prophylactically. In embodiments, the subject is administered methylprednisolone, diphenhydramine, and acetaminophen prophylactically. In embodiments, the effective amount of the anti-CD19 antibody or antigen-binding fragment thereof is about 50 mg to 1000 mg, 100 to 800 mg, 200 to 600 mg, 200 to 500 mg, 250 to 450 mg, 200 to 350 mg, 250 to 350 mg, or 375 to 325 mg. In embodiments, the effective amount is about 50 mg, 100 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the effective amount is about 300 mg. In embodiments, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In embodiments, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In embodiments, the anti-CD19 antibody is a monoclonal antibody. In embodiments, the anti-CD19 antibody is defucosylated. In embodiments, the administration, repeated administration, or both, is effective to clear IMNM for at least about 3 months, 6 months, 1 year, or 2 years. In embodiments, the administration, repeated administration, or both, is effective to stabilize or reduce IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0018] and anti-CD40 antibodies for use in the treatment of immune-mediated necrotizing myopathy (IMNM). and an anti-CD19 antibody or antigen-binding fragment thereof, the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively. Approximately 100 mg to 1000 mg of the anti-CD19 antibody or antigen-binding fragment thereof is administered to a subject in need thereof. Also provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM), comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, wherein approximately 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof is administered to a subject in need thereof. Also provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells in a pediatric subject, the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively. Also provided is inebilizumab for use in treating immune-mediated necrotizing myopathy (IMNM), wherein approximately 100 mg to 1000 mg of inebilizumab is administered to a subject in need thereof.Also provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells, the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, in a subject positive for an autoantibody selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR. Also provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells, the antibody comprising complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is negative for autoantibodies selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR. In one embodiment, administration comprises 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof on days 1 and 15, followed by one 300 mg injection approximately every six months thereafter. Also provided is an anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM), comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and wherein approximately 300 mg is administered every six months, with an initial dose of 300 mg administered two weeks before the first 300 mg administration every six months.In aspects, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In aspects, the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0019] These and other embodiments are described below.

[0020] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate some, but not the only or exclusive, embodiments and / or features. It is intended that the aspects and figures disclosed herein be considered illustrative rather than limiting. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 shows an exemplary study flow diagram for a study with a randomized controlled period of 26 weeks. [Figure 2] FIG. 1 shows an exemplary study flow diagram for a study with a randomized controlled period of 52 weeks. DETAILED DESCRIPTION OF THE INVENTION

[0022] The present disclosure provides antibodies and antigen-binding fragments thereof that bind to Cluster of Differentiation 19 (CD19, also known as B lymphocyte antigen CD19). Inhibition of binding can reduce or eliminate activation of inflammatory signaling pathways associated with related diseases. In embodiments, the anti-CD19 antibodies and antigen-binding fragments thereof disclosed herein can be used to neutralize CD19. In embodiments, the anti-CD19 antibodies and antigen-binding fragments thereof disclosed herein can be used to regulate B cell activity. Polypeptides comprising anti-CD19 antibodies and antigen-binding fragments thereof are provided herein. Disclosed herein are methods for improving quality of life associated with myopathy using anti-CD19 antibodies and antigen-binding fragments thereof. In embodiments, the anti-CD19 antibodies and antigen-binding fragments thereof disclosed herein can be used to treat myopathy. In embodiments, the anti-CD19 antibodies and antigen-binding fragments thereof disclosed herein can be used to treat immune-mediated necrotizing myopathy (IMNM).

[0023] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this subject matter pertains. All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. The materials, methods, and examples disclosed herein are merely illustrative and are not intended to be limiting.

[0024] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0025] The term "about" or "approximately," when immediately preceding a numerical value, denotes a range (e.g., plus or minus 10% of that value). For example, "about 50" can mean 45 to 55, and "about 25,000" can mean 22,500 to 27,500, unless the context of this disclosure dictates otherwise or contradicts such an interpretation. For example, in a list of numerical values ​​such as "about 49, about 50, about 55, ...," "about 50" means a range extending to less than half the interval between the preceding and following values, e.g., greater than 49.5 to less than 52.5. Furthermore, the phrase "less than about" a value or "greater than about" a value should be understood in light of the definition of the term "about" provided herein. Similarly, the term "about," when preceding a series of numerical values ​​or ranges of values ​​(e.g., "about 10, 20, 30," or "about 10 to 30"), refers to the endpoints of all values ​​or ranges in the series, respectively.

[0026] As used herein, the term "subject" refers to any subject, e.g., a human or non-human mammal, for whom diagnosis, prognosis, or therapy is desired. The term "subject" refers to a human or non-human mammal that is suffering from, may be suffering from, or is suspected of being suffering from a disease. It may refer to a mammal. The terms "subject" and "subjects" are used interchangeably herein. In embodiments, the subject is a mammal. Mammals include primates such as humans, monkeys, chimpanzees, and apes, as well as non-primates such as laboratory animals (rabbits and rodents, e.g., guinea pigs, rats, or mice) and domestic animals, including household pets and livestock (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits), and non-domestic animals such as wildlife, birds, reptiles, fish, etc. The subject may be a child.

[0027] As used herein, the term "subject in need thereof" includes a subject who may or would benefit from the methods described herein. Subjects in need of treatment include, but are not limited to, subjects already with a condition or disorder, subjects prone to having a condition or disorder, subjects suspected of having a condition or disorder, and subjects in whom a condition or disorder needs to be prevented, ameliorated, or reversed.

[0028] As used herein, "treating" or "treat" describes the management and care of a subject for the purpose of combating a disease, condition, or disorder, and includes administering an anti-CD19 antibody or antigen-binding fragment thereof used in the methods described herein to alleviate the symptoms or complications of the disease, condition, or disorder, or to eliminate the disease, condition, or disorder. Thus, the term "treat" or "treating" refers to both therapeutic and prophylactic or preventative measures, the objective of which is to prevent, slow (alleviate), or ameliorate the progression of a disease (e.g., myositis or myopathy). Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, reduction in the extent of disease, stabilization (i.e., non-worsening) of disease, delay or slowing of disease progression, improvement or palliation of the disease state, and reversal of disease (whether partial or total).

[0029] When referring to protein sequences, the term "identity" is used to indicate the similarity between two sequences. Unless otherwise indicated, the percent identity described herein is determined using the BLAST algorithm, available on the World Wide Web at the following address: blast.ncbi.nlm.nih.gov / Blast.cgi, using default parameters.

[0030] Cluster of differentiation 19 (CD19) binding protein In some embodiments, anti-CD19 binding agents are provided herein. The anti-CD19 binding agents can be used in the disclosed therapeutic regimens for treating myositis (e.g., IMNM). IMNM is a debilitating, rapidly progressive form of idiopathic inflammatory myopathy that significantly impacts patients' muscle strength and functional activity. IMNM has been identified as an important and unique disease with specific serological, clinical, and pathological diagnostic criteria (Allenbach et al., 2018). IMNM is characterized by proximal muscle weakness, often the only clinical symptom, and elevated creatine kinase (CK) levels. IMNM manifests as three distinct subtypes depending on autoantibody status: signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl-coenzyme A reductase-antibody positive (HMGCR-Ab+), or negative for both SRP-Ab and HMGCR-Ab (seronegative).

[0031] In embodiments, a therapeutic regimen including any of the disclosed anti-CD19 binding agents results in the reduction or elimination of B cells in a subject in need thereof. Because B cells, particularly plasmablasts and plasma cells, contribute to disease, reducing or eliminating them is beneficial for subjects with myositis. In embodiments, the anti-CD19 binding agent reduces or eliminates at least one of CD19-positive B cells, plasmablasts, plasma cells, or any combination thereof. In embodiments, the anti-CD19 binding agent comprises an anti-CD19 antibody.

[0032] Exemplary sequences of anti-CD19 antibodies and antigen-binding fragments thereof are shown in Table 1. In embodiments, the anti-CD19 antibodies and antigen-binding fragments thereof have at least or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about any one of SEQ ID NOs: 1-10 shown in Table 1. inIn embodiments, any one of the sequences in Table 1 can be modified. In embodiments, modifications include one or more truncations, deletions, insertions, and combinations thereof. Modifications can occur at any of the residues provided in Table 1 and at any number of residues from Table 1. In embodiments, modifications can include 1 to 3, 1 to 5, 1 to 10, 1 to 20, 3 to 8, 3 to 10, 3 to 15, 5 to 8, 5 to 10, or 5 to 20 residues. In embodiments, modifications can include up to in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, or maximum in This can occur at residue 450.

[0033] [Table 1-1]

[0034] [Table 1-2]

[0035] In some embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof of the present disclosure may include sequence variants as long as they retain the ability to bind to CD19. For example, conservative amino acid substitutions can be made in any one of the disclosed CDRs. Various modifications can be made according to the methods described in Antibody Engineering, 2nd ed., Oxford University Press, ed. Borrebaeck, 1995. These modifications include, but are not limited to, nucleotide sequences that are altered by substitution of different codons that encode functionally equivalent amino acid residues within the sequence, thus producing "silent" changes. For example, nonpolar amino acids include alanine (A), leucine (L), isoleucine (I), valine (V), proline (P), phenylalanine (F), tryptophan (W), and methionine (M). Polar neutral amino acids Acids include glycine (G), serine (S), threonine (T), cysteine ​​(C), tyrosine (Y), asparagine (N), and glutamine (Q). Positively charged (basic) amino acids include arginine (R), lysine (K), and histidine (H). Negatively charged (acidic) amino acids include aspartic acid (D) and glutamic acid (E). In embodiments, the CDR amino acid sequences (SEQ ID NOS: 2-4, 6-8) disclosed herein are at least about 80%, 85%, 90%, 95%, 96%, variable 97%, 98%, 99%, or up to about 99%. in It can vary by approximately 100%.

[0036] Derivatives and analogs of antibodies or antigen-binding fragments thereof of the present disclosure can be produced by a variety of techniques, including recombinant and synthetic methods (Maniatis (1990) Molecular Cloning, A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, and Bodansky et al. (1995) The Practice of Peptide Synthesis, 2nd ed., Spring Verlag, Berlin, Germany). In embodiments, a method for generating a VH domain that is an amino acid sequence variant of a VH domain of the present disclosure comprises adding, deleting, substituting, or inserting one or more amino acids in the amino acid sequence of a VH domain of the present disclosure, optionally combining the VH domain so provided with one or more VL domains, and testing the VH domain or VH / VL combination for specific binding to antigen. Similar methods can be used to combine one or more sequence variants of a VL domain disclosed herein with one or more VH domains. In embodiments, the amino acid sequences of the VH or VL disclosed herein (SEQ ID NOs: 1 and 5) are at least about 80%, 85%, 90%, 95%, 96%, may vary from 97%, 98%, 99%, or up to about 100%. in It can vary by approximately 100%.

[0037] The present disclosure provides methods for the use of CD19 binding molecules, e.g., antibodies and antigen-binding fragments thereof that bind to CD19. The full-length amino acid sequence and nucleotide sequence of CD19 are known in the art (see, e.g., UniProt Acc. No. Q71UW0 for human CD19). In embodiments, the anti-CD19 antibody is also known as MEDI-551. In embodiments, the anti-CD19 antibody is also known as VIB551. In embodiments, the anti-CD19 antibody is also known as HZN551. In embodiments, the anti-CD19 antibody is also known as UPLIZNA™. In embodiments, the anti-CD19 antibody is also known as inebilizumab. In embodiments, compositions of the present disclosure can include any of the amino acid sequences set forth in PCT Patent Application No. PCT / US2007 / 077916, which is incorporated herein by reference in its entirety (VIB551 is referred to as "16C4" in PCT Patent Application No. PCT / US2007 / 077916). In embodiments, provided compositions can include any of the sequences shown in Table 1.

[0038] In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof disclosed herein can be glycosylated. In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof can have a glycosylation pattern that differs from the wild-type pattern. For example, one or more carbohydrate moieties can be deleted and / or one or more glycosylation sites can be added. Addition of glycosylation sites to the antibodies or antigen-binding fragments of the present disclosure can be achieved by modifying the amino acid sequence to contain glycosylation site consensus sequences known in the art. Another means of increasing the number of carbohydrate moieties on an antibody or antigen-binding fragment is by chemical or enzymatic coupling of glycosides to amino acid residues of the antibody or antigen-binding fragment. Such methods are described in WO 87 / 05330 and Aplin et al. (1981) CRC Crit. Rev. Biochem., 22:259-306. Removal of carbohydrate moieties from an antibody or antigen-binding fragment can be performed, for example, as described by Hakimuddin et al. (1987) ) Arch. Biochem. Biophys., 259:52; and Edge et al. (1981) Anal. Biochem., 118:131 and Thotakura et al. (1987) Meth. Enzymol., 138:350.

[0039] In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof disclosed herein can be aglycosylated. In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof can have a fucosylation pattern that differs from the wild-type pattern. For example, one or more fucose moieties can be deleted. Addition of fucosylation sites to the antibodies or antigen-binding fragments of the present disclosure can be achieved by modifying the amino acid sequence to remove fucosylation site consensus sequences known in the art. Another means of removing any fucose moieties from antibodies or antigen-binding fragments is described, for example, in Hakimuddin et al. (1987) Arch. Biochem. Biophys., 259:52; and Edge This can be accomplished chemically or enzymatically, as described by Thotakura et al. (1981) Anal. Biochem., 118:131 and Thotakura et al. (1987) Meth. Enzymol., 138:350.

[0040] In embodiments, the anti-CD19 binding agent comprises inebilizumab. Inebilizumab is a humanized, affinity-optimized, defucosylated IgG1 kappa monoclonal antibody (mAb) known as 16C-aFuc that binds to the B cell-specific surface antigen CD19 and reduces or eliminates CD19+ B cells. Inebilizumab is glycoengineered by expression of mAb 16C4 in a fucosyltransferase-deficient Chinese hamster ovary producer cell line (BioWa Potelligent® Technology), which produces a uniformly fucosylated antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). In aspects, the anti-CD19 antibodies or antigen-binding fragments thereof described herein mediate ADCC, complement-dependent cell-mediated cytotoxicity (CDC), and / or apoptosis. In aspects, the anti-CD19 antibodies or antigen-binding fragments thereof described herein inhibit anti-IgM / CpG-stimulated B cell proliferation.

[0041] Administration In embodiments, any of the compositions of the present disclosure comprising an anti-CD19 antibody or antigen-binding fragment thereof, and / or any of the conventional therapies disclosed herein can be administered in any form. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof, and / or any of the conventional therapies is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered by injection.

[0042] The anti-CD19 antibodies or antigen-binding fragments thereof of the present disclosure can be administered at any dose. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of from about 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, 1450 mg, or about 1500 mg.

[0043] In some embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered in an amount of about 50-100 mg, 50-150 mg, 100-200 mg, 130-180 mg, 150-250 mg, 20 In some embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of 0-300 mg, 250-350 mg, 50-1500 mg, 75-1200 mg, 100-800 mg, or 150-500 mg. In some embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose selected from the group consisting of 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 500 mg, 525 mg, 550 mg, 575 mg, and 600 mg. In some embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at an effective amount of approximately 300 mg. In some embodiments, 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof is administered. In some embodiments, 300 mg of inebilizumab is administered.

[0044] Methods are also provided that include administering conventional therapy.

[0045] In embodiments, conventional therapy provides at least about or at most about 100 mg of niacin per kg of body weight of the subject. Approximately 0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.5mg, 0.6mg, 0.7mg, 0.8mg, 0.9mg, 1mg, 2mg, 3mg, 4mg, 6mg, 8mg, 10mg, 12mg, 14mg, 15mg, 16mg, 18mg, 20mg, 22mg, 24mg, 26mg, 28mg, 30mg, 32mg, 34mg, 36mg, 38m g, 40mg, 42mg, 44mg, 46mg, 48mg, 50mg, 52mg, 54mg, 56mg, 58mg, 60mg, 62mg, 64mg, 66mg, 68mg, 70mg, 72mg, 74mg, 76mg, 78mg, 80mg, 82mg, 84mg, 86mg, 88mg, 90mg, 92mg, 94mg, 96mg, 98mg, or max. in The dosage is approximately 100 mg. In an embodiment, cyclophosphamide can be administered at about 40 mg to about 50 mg per kg of the subject's body weight. In an embodiment, cyclophosphamide can be administered to the subject for at least about 2 days to about 5 days. In some cases, cyclophosphamide can be administered at about 10 mg to about 15 mg per kg of the subject's body weight. In some cases, cyclophosphamide can be administered to the subject for at least about 7 days to about 10 days. In some cases, cyclophosphamide can be administered at about 3 mg to about 5 mg per kg of the subject's body weight. In some cases, cyclophosphamide can be administered at about 50 mg to about 80 mg per kg of the subject's body weight. In some cases, cyclophosphamide can be administered in an amount greater than 50 mg per kg of the subject's body weight. In some cases, cyclosporine can be administered at about 60 mg per kg of the subject's body weight. In some cases, cyclosporine can be administered at about 15 mg / kg (body weight) per day. In one embodiment, azathioprine can be administered at about 1 mg / kg body weight per day, either as a single dose once daily or in two divided doses. In another embodiment, tacrolimus can be administered at about 0.1 to about 0.2 mg / kg body weight per day.

[0046] In embodiments, conventional therapy is at least about or at most Approximately 1mg, 2mg, 3mg, 4mg, 6mg, 8mg, 10mg, 12mg, 14mg, 16mg, 18mg, 20mg, 22mg, 24mg, 26mg, 28mg, 30mg, 32mg, 34mg, 36mg, 38mg, 40mg, 42mg, 44mg, 46mg, 48mg, 50m g. in Doses of about 100 mg or more can be administered. In embodiments, methotrexate can be administered from about 25 to 75 milligrams once a week. In embodiments, methotrexate can be administered from about 2.5 milligrams two to four times a week. In embodiments, prednisone is administered from about 10 to about 60 mg / day in a single daily dose or in two to four divided doses. In embodiments, prednisone is administered from about 2.5 to 10 mg / day. In embodiments, prednisone is administered from about 1 to 1.5 mg / kg / day.

[0047] In an embodiment, the therapeutic regimen comprises administering an anti-CD19 antibody or antigen-binding fragment thereof. In an embodiment, the therapeutic regimen comprises administering 300 mg of inebilizumab. In an embodiment, the therapeutic regimen comprises administering 100 to 300 mg, 150 to 300 mg, 200 to 400 mg, 250 to 500 mg, or 300 to 500 mg of inebilizumab.

[0048] Any dosage provided may be a dosage effective for methods including prevention, alleviation, or elimination. The dosage provided may also be effective to stabilize, alleviate, or eliminate a disease or its symptoms, as described herein.

[0049] Dosage frequency In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof of the present disclosure are administered on a schedule that provides optimal results. In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof disclosed herein are administered to a subject in need thereof about once per week, about twice per week, about every two weeks, about every four weeks, about once per month, about every six weeks, about every two months, about every three months, about every 12 weeks, about every 15 weeks, about every 16 weeks, about every four months, about every five months, about every six months, or every six months.

[0050] Any number of administrations may be provided to a subject in need thereof. In embodiments, a subject is administered an effective dose daily, weekly, biweekly, or for approximately the subject's lifetime. In embodiments, administration occurs for up to about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, or 5 years. In embodiments, a subject receives an effective dose on days 1, 15, 183, 365, 547, 729, and 911 after initiation of treatment. In embodiments, a subject receives an effective dose on weeks 0, 2, 26, 52, 78, 104, 130, and 156 after initiation of treatment. In embodiments, a subject receives an effective dose of 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof on days 1, 15, 183, 365, 547, 729, and 911 after initiation of treatment. In embodiments, a subject receives an effective dose of 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof on weeks 0, 2, 26, 52, 78, 104, and 130 after initiation of treatment. In embodiments, a subject receives an effective dose of 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof on weeks 0, 2, 26, 52, 78, 104, 130, and 156 after initiation of treatment. In embodiments, a subject in need thereof is administered an effective dose of 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof on day 1, day 15, and every 6 months (or 24 weeks) thereafter as needed. Any of the foregoing administrations can be offset by about 0-7 days, 0-5 days, 0-4 days, 0-3 days, 0-2 days, about 3 days, or about 7 days.

[0051] In embodiments, the subject receives an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof on days 1, 15±3, 183±7, 365±7, and 547±7 after initiation of treatment. In embodiments, the subject receives an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof on days 1, 15±3, 183±7, 365±7, 547±7, and 729±7 after initiation of treatment. In embodiments, the subject receives an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof on days 1, 15±3, 183±7, 365±7, 547±7, 729±7, and 911±7 after initiation of treatment. In embodiments, the subject receives an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof at week 0, week 2 ± 3 days, week 26 ± 3 days, week 52 ± 7 days, week 78 ± 7 days, week 104 ± 7 days, and week 130 ± 7 days after initiation of treatment. ... , 52 weeks ± 7 days, 78 weeks ± 7 days, 104 weeks ± 7 days, 130 weeks ± 7 days, and 156 weeks ± 7 days.

[0052] In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered in a single effective dose. In embodiments, the subject in need thereof is administered at least two doses of the anti-CD19 antibody or antigen-binding fragment thereof.

[0053] In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg for at least one dose, then about once every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg for at least two doses, then about once every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg about once every two weeks, about once every month, about once every two months, about once every three months, once every six months, or once every 12 months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg once every two weeks for two doses, then once every six months for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 doses, or thereafter up to at least 15 doses.

[0054] In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered in two or more doses. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure is administered to a subject in need thereof until myositis is prevented, alleviated, or eliminated, as determined by a test of the present disclosure. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered as an effective dose of about 300 mg. In embodiments, the methods disclosed herein comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof is administered intravenously at an effective dose of about 300 mg. In embodiments, the methods disclosed herein comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof is administered as a single dose of about 300 mg every two weeks for at least two doses, and then about once every six months. In embodiments, methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds CD19, wherein the antibody or antigen-binding fragment thereof is administered as a single dose of about 300 mg for at least two doses every two weeks, followed by about once every six months. In embodiments, methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds CD19, wherein the antibody or antigen-binding fragment thereof is administered as a single dose of about 300 mg for at least two doses every two weeks, followed by about once every six months for 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more doses. In embodiments, methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds CD19, wherein the antibody or antigen-binding fragment thereof is administered intravenously as a single dose of about 300 mg for at least two doses every two weeks, followed by about once every six months.In aspects, the methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof is administered intravenously as a single dose of about 300 mg at least twice every two weeks, followed by 2, 3, 4, 5, 6, 7, 8, 9, or 10 doses or more about once every six months.

[0055] In aspects, the methods disclosed herein comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively. The methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8, respectively, and the antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg for at least two doses, and then approximately once every six months. In an aspect, the methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and wherein the antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg for at least two doses, followed by 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more doses about once every six months. In an aspect, the methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the antibody or antigen-binding fragment thereof is administered intravenously at a dose of approximately 300 mg once every two weeks for two doses, and then approximately once every six months.In an aspect, the methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg once every two weeks for two doses, followed by 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more doses about once every six months.

[0056] In aspects, methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise amino acid sequences having at least about 80%, 85%, 90%, 95%, 99%, or 100% identity to SEQ ID NOs: 1 and 5, respectively, and wherein the antibody or antigen-binding fragment is administered as a dose of about 300 mg. In aspects, methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 1 and 5, respectively, and wherein the antibody or antigen-binding fragment thereof is administered intravenously as a dose of about 300 mg. In aspects, the methods disclosed herein comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 1 and 5, respectively, and the antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg once every two weeks for two doses, followed by administration about every six months for two, three, four, five, six, seven, eight, nine, or ten or more doses. In aspects, the methods disclosed herein include administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, The antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 1 and 5, respectively, and the antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg once every two weeks for two doses, followed by about once every six months. In an aspect, a method disclosed herein comprises administering to a subject in need thereof an antibody or antigen-binding fragment thereof that binds to CD19, wherein the antibody or antigen-binding fragment thereof comprises a VH and a VL, wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 1 and 5, respectively, and the antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg once every two weeks for two doses, followed by about once every six months for 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more doses.

[0057] In embodiments, a subject in need thereof is administered an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof about once every 2-4 weeks. In embodiments, a subject in need thereof is administered an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof about every 24 weeks or once every 6 months. In embodiments, a subject in need thereof is administered an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof once every 2 weeks for two doses, then every 6 months thereafter. In embodiments, a subject in need thereof is administered an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof once every 2 weeks for two doses, then about once every 6 months for 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more doses. In embodiments, a subject in need thereof is administered 300 mg of an anti-CD19 antibody or antigen-binding fragment thereof for at least two doses once every two weeks, at least one dose once every six months, at least two doses once every six months, at least three doses once every six months, at least four doses once every six months, or 2, 3, 4, 5, 6, 7, 8, 9, or 10 doses or more once every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered once every two weeks at an effective dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered every six months at an effective dose of about 300 mg.

[0058] method In aspects herein, methods are directed to treating, alleviating, or eliminating a myositis disease or disorder. In aspects, the method comprises administering an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. In aspects, the anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate myositis in a subject in need thereof using any of the administration schedules disclosed herein. In aspects, the myopathic disease or disorder comprises immune-mediated necrotizing myopathy (IMNM). In aspects, the anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate IMNM in a subject in need thereof using any of the administration schedules disclosed herein. In aspects, the anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, alleviate, or eliminate disease in a subject who tests positive for anti-signal recognition particle (e.g., anti-SRP) antibodies prior to treatment. In embodiments, an anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject who tests positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (e.g., anti-HMGCR) antibodies prior to treatment. In embodiments, an anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject who is diagnosed with IMNM and tests positive for anti-signal recognition particle (e.g., anti-SRP) antibodies prior to treatment. In embodiments, an anti-CD19 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject who is diagnosed with IMNM and tests positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (e.g., anti-HMGCR) antibodies prior to treatment.

[0059] In embodiments, a method of treating a subject in need thereof comprises administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the administration is to treat a) a disease or disorder in an otherwise equivalent subject lacking the administration; or b) a disease or disorder in a subject in need thereof. In embodiments, the administration is effective to reduce the level of CD19+ B cells in a subject in need thereof compared to the subject's baseline level. In embodiments, the level of CD19+ B cells is at least about or at most 50% in a subject administered the anti-CD19 antibody or antigen-binding fragment compared to the subject's baseline level. about 3 fold, 5-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold decrease. In embodiments, the level of CD19+ B cells is reduced by at least about or at most 1 / 2 times in a subject administered an anti-CD19 antibody or antigen-binding fragment, compared to the subject's baseline level. about 5 %, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or max in It decreases by about 100%.

[0060] In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof are used to treat a myositis disease or disorder. In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof are used to treat a subject in need thereof using any of the dosing schedules disclosed herein.

[0061] In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered every two weeks at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered every six months at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at least two doses every two weeks at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered at least or at most four doses every six months at a dose of about 300 mg. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered two doses every two weeks at a dose of about 300 mg, followed by at least or at most four doses every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg for at least two doses every two weeks. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg for at least or at most four doses every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg for at least two doses every two weeks, followed by at least or at most four doses every six months. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered intravenously at a dose of about 300 mg for at least two doses every two weeks, followed by every six months.

[0062] In embodiments, compositions comprising anti-CD19 antibodies or antigen-binding fragments thereof are formulated for administration. In embodiments, the anti-CD19 antibodies or antigen-binding fragments thereof are at least about or at most Approximately 1mg / mL, 2mg / mL, 3mg / mL, 4mg / mL, 5mg / mL, 6mg / mL, 7mg / mL, 8mg / mL, 9mg / mL, 10mg / mL, 15mg / mL, 20mg / mL, 25mg / mL, 30mg / mL, 35mg / mL, 40mg / mL, 45mg / mL, 50 mg / mL, 55mg / mL, 60mg / mL, 65mg / mL, 70mg / mL, 75mg / mL, 80mg / mL, 85mg / mL, 90mg / mL, 95mg / mL, 100mg / mL, 105mg / mL, 110mg / mL, 115mg / mL, 120mg / mL, 125mg / mL, 130mg / mL, 135mg / mL, 140mg / mL, 145mg / mL, 150mg / mL, 155mg / mL, 160mg / mL, 165mg / mL, 170mg / mL, 175mg / mL, 180mg / mL, 185mg / mL, 190mg / mL, 195mg / m L, 200mg / mL, 205mg / mL, 210mg / mL, 215mg / mL, 220mg / mL, 225mg / mL, 230mg / mL, 235mg / mL, 240mg / mL, 245mg / mL, 250mg / mL, 255mg / mL, 260mg / mL, 265mg / mL, 270mg / mL, 275mg / mL, 280mg / mL, 285mg / mL, 290mg / mL, 295mg / mL, or maximum in It is formulated at a concentration of about 300 mg / mL. In embodiments, an effective dose of an anti-CD19 antibody or antigen-binding fragment thereof can be formulated at a concentration of about 10 mg / mL.

[0063] The doses and administration regimens of the anti-CD19 antibodies or antigen-binding fragments thereof disclosed herein can be such that the therapeutic effect achieved from administering the anti-CD19 antibodies or antigen-binding fragments thereof to treat any myopathic disease or disorder is considered to be "long-lasting." A "long-lasting" effect of an anti-CD19 antibody or antigen-binding fragment thereof in the treatment of a myositis disease or disorder is one in which the therapeutic effect achieved by the anti-CD19 antibody or antigen-binding fragment thereof is maintained for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 32 weeks, at least 36 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks, at least 1 year, at least 2 years, at least 3 years, at least 4 years, or up to at least about 5 years after prior administration of the anti-CD19 antibody or antigen-binding fragment thereof.

[0064] In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate disease in a subject in need thereof. In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to alleviate disease in a subject in need thereof. Optionally, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate or alleviate disease in a subject in need thereof for at least about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, at least about 5 years, or for the lifetime of the subject. In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate disease in a subject in need thereof for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or at least about 12 weeks. In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate or reduce disease in a subject in need thereof for at least about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or at least about 12 months. In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate or reduce disease in a subject in need thereof for at least about 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, or at least about 10 years. In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof is effective to eliminate or reduce disease for the lifetime of the subject in need thereof.

[0065] In embodiments, a subject in need thereof has been administered one or more conventional therapies for treating a myositis disease or disorder prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the conventional therapies include corticosteroids, immunomodulators, and / or analgesics. In embodiments, the subject continues the conventional therapy while receiving the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the conventional therapy is administered as a second therapy. In embodiments, any of the mentioned therapies may be combined in a treatment regimen for treating a myositis disease or disorder. In embodiments, the subject is treated with both the anti-CD19 antibody or antigen-binding fragment thereof and the conventional therapy.

[0066] The methods of the present disclosure can include tapering one or more conventional therapies and / or anti-CD19 antibodies or antigen-binding fragments thereof. In embodiments, the methods include tapering a conventional therapy. In embodiments, the method comprises tapering the corticosteroid. In embodiments, the method comprises tapering the methylprednisolone. In embodiments, the method comprises tapering the prednisone. The tapering can occur at any time. In embodiments, the tapering occurs prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the tapering occurs concurrently with administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the tapering occurs after administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the tapering comprises reducing the frequency of use by at least about 10%, 15%, 20%, 25%, 30%, 40%, or 50%. In embodiments, the tapering is a reduction in daily dosage from about ≧10 mg to 7.5 mg. In embodiments, the tapering occurs about every two weeks, beginning at week 26.

[0067] Corticosteroids In embodiments, the subject is administered a corticosteroid. In embodiments, the subject is administered a corticosteroid in combination with an anti-CD19 antibody or antigen-binding fragment thereof disclosed in any of the methods herein. In embodiments, the corticosteroid comprises a glucocorticoid. Glucocorticoids (GCs) are steroid hormones used in the treatment of inflammatory, myositis, and / or cancer diseases or disorders. To exert their wide range of physiological and therapeutic effects, GCs bind to the GC receptor (GR), which belongs to the nuclear receptor superfamily of transcription factors. In embodiments, one or more GCs are administered to a subject in need thereof. In embodiments, the one or more GCs are selected from the group consisting of, but not limited to, triamcinolone, methylprednisolone, budesonide, dexamethasone, prednisone, hydrocortisone, betamethasone, prednisolone, deflazacort, and combinations thereof. In embodiments, the GC is prednisone. In embodiments, the GC is methylprednisolone.

[0068] immunomodulators In embodiments, the subject is administered an immunomodulatory agent. In embodiments, the immunomodulatory agent is a nonsteroidal immunosuppressant (IST). In embodiments, the subject is administered an immunosuppressant in combination with an anti-CD19 antibody or antigen-binding fragment thereof disclosed in any of the methods herein. Immunomodulatory agents include methotrexate, cyclophosphamide, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, sirolimus, everolimus, and combinations thereof. In embodiments, the immunomodulatory agent is methotrexate. In embodiments, the immunomodulatory agent is cyclophosphamide. In embodiments, the immunomodulatory agent is azathioprine. In embodiments, the immunomodulatory agent is mycophenolate mofetil. In embodiments, the immunomodulatory agent is mycophenolic acid. In embodiments, the immunomodulatory agent is tacrolimus. In embodiments, the immunomodulatory agent is cyclosporine.

[0069] painkillers In embodiments, the subject is administered an analgesic. In embodiments, the subject is administered an analgesic in combination with an anti-CD19 antibody or antigen-binding fragment thereof disclosed in any of the methods herein. Analgesics include NSAIDs, acetaminophen, corticosteroids, opioids (e.g., codeine, fentanyl, vicodin, morphine, oxycodone, Percocet), antidepressants, antihistamines (e.g., diphenhydramine or cetirizine), anticonvulsants, lidocaine, and combinations thereof. In embodiments, the analgesic is acetaminophen. In embodiments, the analgesic is an antihistamine.

[0070] In embodiments, any conventional therapy is combined as part of a treatment regimen or combination therapy. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered sequentially with any therapy disclosed herein. In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof may generally be administered simultaneously with any second therapy disclosed herein. In embodiments, a subject in need thereof may receive a steroid therapy after administration of an anti-CD19 antibody or antigen-binding fragment thereof. Prior to administration, the patient has been receiving conventional therapy to treat the myositis disease or disorder.

[0071] In embodiments, the one or more conventional therapies are administered about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 13 weeks, about 14 weeks, about 15 weeks, about 20 weeks, about 25 weeks, about 30 weeks, about 35 weeks, about 40 weeks, about 52 weeks, or more than about 52 weeks prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the one or more conventional therapies are administered about 2 weeks prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the one or more conventional therapies are administered about 12 weeks prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof.

[0072] The doses and administration regimens of the anti-CD19 antibodies or antigen-binding fragments thereof disclosed herein can be such that the therapeutic effect achieved from administering the anti-CD19 antibodies or antigen-binding fragments thereof to treat any myopathic disease or disorder is considered to be "long-lasting." A "long-lasting" effect of an anti-CD19 antibody or antigen-binding fragment thereof in treating a myopathic disease or disorder means that the therapeutic effect achieved by the anti-CD19 antibody or antigen-binding fragment thereof continues for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 32 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 32 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 12 weeks, at least 14 ... The anti-CD19 antibody or antigen-binding fragment thereof (while the anti-CD19 antibody or antigen-binding fragment thereof is no longer administered) may be maintained for more than 6 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks, at least 52 weeks, at least 56 weeks, at least 60 weeks, at least 64 weeks, at least 68 weeks, at least 72 weeks, at least 76 weeks, at least 80 weeks, at least 84 weeks, at least 88 weeks, at least 92 weeks, at least 96 weeks, at least 100 weeks, or at least 104 weeks. In some embodiments, it may be advantageous to administer any of the compositions provided herein less frequently. Exemplary benefits of less frequent administration include, but are not limited to, a reduced frequency of side effects associated with the administered composition, reduced treatment-related toxicity, and improved quality of life for the treated subject.

[0073] evaluation In embodiments, a subject is evaluated. In embodiments, a subject is evaluated as part of a treatment. In embodiments, a subject with a confirmed or possible myopathic disease or disorder is evaluated as part of a treatment. The evaluation can occur at any time before, during, or after administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the evaluation occurs before administration begins. In embodiments, the evaluation occurs simultaneously with administration. In embodiments, the evaluation occurs after administration has ended.

[0074] In embodiments, the evaluation can be performed at any time before, during, or after administration of the anti-CD19 antibody or antigen-binding fragment thereof as part of a Phase 2 trial. In embodiments, the evaluation can be performed at any time before, during, or after administration of the anti-CD19 antibody or antigen-binding fragment thereof as part of a Phase 3 trial. In embodiments, the evaluation can be performed at any time before, during, or after administration of the anti-CD19 antibody or antigen-binding fragment thereof as part of an open-label period (OLP, also known as open-label continuous administration; OLE).

[0075] In embodiments, the subject is evaluated and a baseline measure of disease is determined. In embodiments, the subject is evaluated and a baseline measure of disease is determined any time before, during, or after administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the evaluation is performed: A baseline measure of disease is determined prior to administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, an assessment is performed and a baseline measure of disease is determined concurrently with administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, an assessment is performed and a baseline measure of disease is determined after administration of the anti-CD19 antibody or antigen-binding fragment thereof.

[0076] In embodiments, baseline disease measurements increase or decrease in response to administration or lack thereof of the present disclosure. In embodiments, baseline disease measurements increase and may indicate effective treatment of the disease or disorder. In embodiments, baseline disease measurements decrease and may indicate effective treatment of the disease or disorder. In embodiments, baseline disease measurements increase or decrease after administration of an anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, baseline disease measurements increase after administration of an anti-CD19 antibody or antigen-binding fragment thereof, which may indicate effective treatment of the disease or disorder. In embodiments, baseline disease measurements decrease after administration of an anti-CD19 antibody or antigen-binding fragment, which may indicate effective treatment of the disease or disorder.

[0077] In embodiments, baseline disease measurements are compared to subject disease measurements after administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, disease measurements in subjects administered the anti-CD19 antibody or antigen-binding fragment thereof are increased compared to baseline disease measurements measured before administration of the anti-CD19 antibody or antigen-binding fragment. In embodiments, disease measurements in subjects administered the anti-CD19 antibody or antigen-binding fragment thereof are decreased compared to baseline disease measurements measured before administration of the anti-CD19 antibody or antigen-binding fragment. In embodiments, disease measurements in subjects administered the anti-CD19 antibody or antigen-binding fragment thereof are increased compared to baseline disease measurements measured before administration of the anti-CD19 antibody or antigen-binding fragment, indicating effective treatment. In embodiments, disease measurements in subjects administered the anti-CD19 antibody or antigen-binding fragment thereof are decreased compared to baseline disease measurements measured before administration of the anti-CD19 antibody or antigen-binding fragment, indicating effective treatment.

[0078] In embodiments, the evaluation includes determining therapeutic efficacy. Efficacy may be determined by any of the evaluations disclosed herein. In embodiments, efficacy in preventing, reducing, or eliminating a myopathic disease or disorder (e.g., IMNM) is determined by detecting a change in baseline blood levels of B cells in the subject. In embodiments, efficacy in preventing, reducing, or eliminating a myopathic disease or disorder is determined by evaluating pharmacokinetic parameters of an anti-CD19 antibody or antigen-binding fragment thereof used to treat a subject in need thereof, a change in baseline blood levels of B cells in the subject, the presence of anti-drug antibodies (ADAs), and combinations thereof. In embodiments, efficacy in preventing, reducing, or eliminating a myopathic disease or disorder is determined by determining pharmacokinetic parameters of an anti-CD19 antibody or antigen-binding fragment thereof used to treat a subject in need thereof. In embodiments, efficacy in preventing, reducing, or eliminating a myopathic disease or disorder is determined by determining a change in baseline blood levels of B cells in the subject. In embodiments, efficacy in preventing, reducing, or eliminating a myositis disease or disorder is also determined by determining the presence of ADAs. In an embodiment, the myositis disease or disorder includes IMNM.

[0079] Any of the assessments mentioned below can be performed at any time. In embodiments, subjects are assessed every minute, hour, day, week, month, quarter, or year. In embodiments, assessments are completed twice daily, every two weeks, every two months, or every six months.

[0080] In embodiments, assessments are made on days -28, -27, -26, -25, -24, -23, -22, -21, -20, -19, 18, -19, or -20 days of treatment. Day 7, -16, -15, -14, -13, -12, -11, -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 , 34th day, 35th day, 36th day, 37th day, 38th day, 39th day, 40th day, 41st day, 42nd day, 43rd day, 44th day, 45th day, 46th day, 47th day, 48th day, 49th day, 50th day, 51st day, 52nd day, 53rd day, 54th day, 55th day, 56th day, 57th day, 58th day, 59th day, 60th day, 61st day, 62nd day, 63rd day, 64th day, 65th day, 66th day, 67th day, 68th day, 69th day, 70th day, 71st day, 72nd day, 73rd day, 74th day, 75th day, 76th day, 77th day, 78th day, 79th day, 80th day, 81st day, 82nd day, 83rd day , 84th, 85th, 86th, 87th, 88th, 89th, 90th, 91st, 92nd, 93rd, 94th, 95th, 96th, 97th, 98th, 99th, 100th, 101st, 102nd, 103rd, 104th, 105th, 106th, 107th, 108th, 109th, 110th, 111th, 112th, 113th, 114th, 115th, 116th, 117th, 118th, 119th, 120th, 121st, 122nd, 123rd, 124th, 125th, 126th, 127th, Day 28, Day 129, Day 130, Day 131, Day 132, Day 133, Day 134, Day 135, Day 136, Day 137, Day 138, Day 139, Day 140, Day 141, Day 142, Day 143, Day 144, Day 145, Day 146, Day 147, Day 148, Day 149, Day 150, Day 151, Day 152, Day 153, Day 154, Day 155, Day 156, Day 157, Day 158, Day 159, Day 160, Day 161, Day 162, Day 163, Day 164, Day 165, Day 166, Day 167, Day 168, Day 169,Day 170, Day 171, Day 172, Day 173, Day 174, Day 175, Day 176, Day 177, Day 178, Day 179, Day 180, Day 181, Day 182, Day 183, Day 184, Day 185, Day 186, Day 187, Day 188, Day 189, Day 190, Day 191, Day 192, Day 193, Day 194, Day 195, Day 196, Day 197, Day 198, Day 199, Day 200, Day 201, Day 202, Day 203, Day 204, Day 205, Day 206, Day 207, Day 208, Day 209, Day 210, Day 211 Day 212, Day 213, Day 214, Day 215, Day 216, Day 217, Day 218, Day 219, Day 220, Day 221, Day 222, Day 223, Day 224, Day 225, Day 226, Day 227, Day 228, Day 229, Day 230, Day 231, Day 232, Day 233, Day 234, Day 235, Day 236, Day 237, Day 238, Day 239, Day 240, Day 241, Day 242, Day 243, Day 244, Day 245, Day 246, Day 247, Day 248, Day 249, Day 250, Day 251, Day 252, Day 25 Day 3, Day 254, Day 255, Day 256, Day 257, Day 258, Day 259, Day 260, Day 261, Day 262, Day 263, Day 264, Day 265, Day 266, Day 267, Day 268, Day 269, Day 270, Day 271, Day 272, Day 273, Day 274, Day 275, Day 276, Day 277, Day 278, Day 279, Day 280, Day 281, Day 282, Day 283, Day 284, Day 285, Day 286, Day 287, Day 288, Day 289, Day 290, Day 291, Day 292, Day 293, Day 294, Day 295, Day 296, Day 297, Day 298, Day 299, Day 300, Day 301, Day 302, Day 303, Day 304, Day 305, Day 306, Day 307, Day 308, Day 309, Day 310, Day 311, Day 312, Day 313, Day 314, Day 315, Day 316, Day 317, Day 318, Day 319, Day 320, Day 321, Day 322, Day 323, Day 324, Day 325, Day 326, Day 327, Day 328, Day 329, Day 330, Day 331, Day 332, Day 333, Day 334, Day 335, Day 336,Day, 337th day, 338th day, 339th day, 340th day, 341st day, 342nd day, 343rd day, 344th day, 345th day, 346th day, 347th day, 348th day, 349th day, 350th day, 351st day, 352nd day, 353rd day, 354th day, 355th day, 356th day, 357th day, 358th day, 359th day, 360th day, 361st day, 362nd day, 363rd day, 364th day, 365th day, 366th day, 367th day, 368th day, 369th day, 370th day, 371st day, 372nd day, 373rd day, 374th day, 375th day, 376th day, 377th day, Day 378, Day 379, Day 380, Day 381, Day 382, ​​Day 383, Day 384, Day 385, Day 386, Day 387, Day 388, Day 389, Day 390, Day 391, Day 392, Day 393, Day 394, Day 395, Day 396, Day 397, Day 398, Day 399, Day 400, Day 401, Day 403, Day 405, Day 407, Day 409, Day 411, Day 413, Day 415, Day 417, Day 419, Day 421, Day 423, Day 425, Day 427, Day 429, Day 431, Day 433, Day 435, Day 437 Day 439, Day 441, Day 443, Day 445, Day 447, Day 449, Day 451, Day 453, Day 455, Day 457, Day 459, Day 461, Day 463, Day 465, Day 467, Day 469, Day 471, Day 473, Day 475, Day 477, Day 479, Day 481, Day 483, Day 485, Day 487, Day 489, Day 491, Day 493, Day 495, Day 497, Day 499, Day 501, Day 503, Day 505, Day 507, Day 509, Day 511, Day 513, Day 515, Day 517, Day 519, Day 52 Day 1, Day 523, Day 525, Day 527, Day 529, Day 531, Day 533, Day 535, Day 537, Day 539, Day 541, Day 543, Day 545, Day 547, Day 549, Day 551, Day 553, Day 555, Day 557, Day 559, Day 561, Day 563, Day 565, Day 567, Day 569, Day 571, Day 573, Day 575, Day 577, Day 579, Day 581, Day 583, Day 585, Day 587, Day 589, Day 591, Day 593, Day 595, Day 597, Day 599, Day 601, Day 603,Day 605, Day 607, Day 609, Day 611, Day 613, Day 615, Day 617, Day 619, Day 621, Day 623, Day 625, Day 627, Day 629, Day 631, Day 633, Day 635, Day 637, Day 639, Day 641, Day 643, Day 645, Day 647, Day 649, Day 651, Day 653, Day 655, Day 657 Day 659, Day 661, Day 663, Day 665, Day 667, Day 669, Day 671, Day 673, Day 675, Day 677, Day 679, Day 681, Day 683, Day 685, Day 687, Day 689, Day 691, Day 693, Day 695, Day 697, Day 699, Day 701, Day 703, Day 705, Day 707, Day 709, Day 711 Day, 713th, 715th, 717th, 719th, 721st, 723rd, 725th, 727th, 729th, 731st, 733rd, 735th, 737th, 739th, 741st, 743rd, 745th, 747th, 749th, 751st, 753rd, 755th, 757th, 759th, 761st, 763rd, 7 The assessments are performed on days 65, 767, 769, 771, 773, 775, 777, 779, 781, 783, 785, 787, 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, 811, or up to about day 813. The timing of the assessments is further described below.

[0081] Evaluating the Choices In embodiments, a subject in need thereof is evaluated prior to initiating treatment. Exemplary evaluation or selection criteria include subjects with one or more myopathic diseases or disorders.

[0082] In embodiments, the subject in need thereof may be male or female. In embodiments, the subject in need thereof is an adult subject. In embodiments, the subject in need thereof may be between about 16 and 80 years of age.

[0083] In embodiments, a subject in need thereof may have a diagnosis of myopathy, including, but not limited to, immune-mediated necrotizing myopathy (IMNM). In embodiments, a subject in need thereof has been diagnosed with IMNM. In embodiments, a subject in need thereof has been diagnosed with IMNM and tests positive for anti-single particle receptor (anti-SPR) or anti-3-hydroxy-3-methyl-glutaryl coenzyme A reductase (anti-HMGCR) antibodies prior to initiating treatment. In embodiments, a subject in need thereof has a creatine kinase (CK) level >1000 U / L. In embodiments, a subject in need thereof has a Manual Muscle Test 8 (MMT-8) score of ≦136 units.

[0084] In embodiments, a subject in need thereof has a diagnosis of definite or probable myopathy according to the American College of Rheumatology (ACR) criteria. In embodiments, a subject in need thereof has a diagnosis of definite or probable myopathy according to the European League against Rheumatism (EULAR) criteria. In embodiments, a subject in need thereof has a diagnosis of definite or probable myositis according to the 2016 ACR / EULAR Total Improvement Score (TIS) criteria.

[0085] In embodiments, a subject in need thereof may have received previous therapy and / or concomitant therapy for the treatment of a myopathic disorder at the time of treatment initiation. In embodiments, a subject in need thereof may have received a stable dose of methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and / or cyclosporine for at least 12 weeks prior to initiating treatment. In embodiments, a subject in need thereof may have received a stable dose of corticosteroids (e.g., prednisone or methylprednisolone) for at least 2 weeks prior to initiating treatment.

[0086] 2016 American College of Rheumatology / European League Against Rheumatism (ACR / EULAR) Total Improvement Score (TIS) In embodiments, the assessment comprises the 2016 ACR / EULAR TIS. In embodiments, the 2016 ACR / EULAR TIS is a validated method for assessing myopathy. In embodiments, the 2016 ACR / EULAR TIS is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 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, and max. in The score may be about 100. In embodiments, the 2016 ACR / EULAR TIS is about 1-10, about 10-30, about 20-40, about 30-50, about 40-60, about 50-70, about 60-80, about 70-90, or about 80-100. The 2016 ACR / EULAR TIS may be ≧20, ≧30, ≧40, ≧50, or ≧60. In embodiments, the criteria may be used as a continuous outcome measure using the 2016 ACR / EULAR TIS. In embodiments, the criteria may be used as a categorical outcome of improvement (minimal, moderate, or large improvement). In embodiments, the criteria may be used as both a continuous outcome measure and a categorical outcome of improvement, thus being a hybrid measure. In embodiments, a change from baseline is determined. In embodiments, the subject's score is increased compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof.

[0087] In embodiments, the 2016 ACR / EULAR for an anti-CD19 antibody or antigen-binding fragment thereof TIS assessments were performed approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, and 15 weeks after the start of treatment. The anti-CD19 antibody or antigen-binding fragment thereof can be evaluated at 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. TIS assessments were performed on approximately days −28, −27, −26, −25, −24, −23, −22, −21, −20, −19, −18, −17, −16, −15, −14, −13, −12, −11, −10, −9, −8, −7, −6, −5, and 6 days after the start of treatment. Assessments can be made on day -4, day -3, day -2, day -1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 22 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, week 42 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, and week 104 ± 7 days.

[0088] Manual Muscle Test 8 (MMT8) bilateral In embodiments, the assessment includes MMT8 bilateral. In embodiments, MMT8 bilateral is a set of eight designated muscles tested bilaterally (MMT8, 2007). In embodiments, axial (neck flexor) testing is included, resulting in a maximum potential MMT8 score of at least about 150. In embodiments, MMT8 bilateral scores are approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 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, , 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, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 1 It can be 0, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 148, or about 150. In an embodiment, both MMT8 ends are about 0 to 10, about 10 to 30, about 20 to 40, about 30 to 50, about 40 to 60, about 50 to 70, about 60 to 80, about 70 to 90, about 80 to 100, about 90 to 110, about 100 to 120, about 110 to 130, about 120 to 140, or about 130 to 150. In embodiments, the MMT8 two-sided assessment can include evaluating a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's MMT8 two-sided score is increased compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.In aspects, administration of an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure increases a subject's MMT8 score to at least about or at most about 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 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%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 1 5%, 90%, 95%, 96%, 97%, 98%, 99% or maximum in It is effective in improving by about 100%.

[0089] In embodiments, the MMT8 bilateral assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks prior to the start of treatment. The administration of the compound can be evaluated at 12 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, the MMT8 bilateral assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about day −28, day −27, day −26, day −25, day −24, day −23, day −22, day −21, day −20, day −19, day −18, day −17, day −16, day −15, day −14, day −13, day −12, day −11, day −10, day −9, day −8 from the start of treatment. The patient may be evaluated at week 1, day −7, day −6, day −5, day −4, day −3, day −2, day −1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 22 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, week 42 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, and week 104 ± 7 days.

[0090] Pulmonary function tests (PFTs) In embodiments, the assessment includes PFTs. PFTs may assess pulmonary function. Pulmonary function may be assessed by measuring tidal volume (TV), minute volume (MV), vital capacity (VC), functional residual capacity (FRC), residual volume, total lung capacity, forced vital capacity (FVC), forced expiratory volume (FEV), forced expiratory flow (FEF), or peak expiratory flow rate (PEFR), or a combination thereof. In embodiments, these assessments may be tested using spirometry, or plethysmography, or a combination of both. In embodiments, PFT scores are improved after treatment with a composition provided herein. In embodiments, PFTs may include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's symptoms are improved compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0091] In aspects, PFTs to the anti-CD19 antibody or antigen-binding fragment thereof are measured at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, 67 days, 68 days, 6 The administration may be evaluated at 2 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, PFTs against an anti-CD19 antibody or antigen-binding fragment thereof are administered at the start of treatment. Approximately -28th day, -27th day, -26th day, -25th day, -24th day, -23rd day, -22nd day, -21st day, -20th day, -19th day, -18th day, -17th day, -16th day, -15th day, -14th day, -13th day, -12th day, -11th day, -10th day, -9th day, -8th day, -7th day, -6th day, -5th day, -4th day, Assessments can be made on day -3, day -2, day -1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 22 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, week 42 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, and week 104 ± 7 days.

[0092] Timed Up and Go (TUG) test In embodiments, the evaluation includes a TUG test. The TUG test can assess mobility. In embodiments, mobility can be assessed by observing a subject's stability, gait, stride length, or sway, or a combination thereof. In embodiments, the evaluation can be performed using a timed task. In embodiments, the TUG test tests a subject's ability to complete a timed task. In embodiments, a subject with a score of ≥ 12 seconds on the timed task has an inadequate score on the timed task. In embodiments, the TUG test time is decreased and thus improved after treatment with a composition provided herein. In embodiments, the TUG test can include evaluating a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's score is improved compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0093] In embodiments, TUG assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, The administration may be evaluated at 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, TUG assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0094] 2-minute walk test (2MWT) In embodiments, the assessment includes a 2MWT. The 2MWT may assess walking ability or functional ability, or a combination of both. In embodiments, the 2MWT may be tested using a timed task. In embodiments, the 2MWT measures the distance a subject walks in two minutes. In embodiments, the 2MWT distance is increased after treatment with a composition provided herein. In embodiments, the 2MWT may include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's distance is improved compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0095] In embodiments, the 2MWT for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about days −28, −27, −26, −25, −24, −23, −22, −24. 1 day, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1, 2, 3, 4, 5, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, The evaluation can be performed at 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, 2MWT assessments for an anti-CD19 antibody or antigen-binding fragment thereof may be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0096] Short Form 12 (SF12) or 36 (SF36) survey In embodiments, the assessment includes an SF12 or SF36 survey. The SF12 or SF36 survey may assess a subject's quality of life. In embodiments, the SF12 or SF36 survey is a self-reported survey. In embodiments, the SF12 or SF36 survey assesses limitations in physical activity due to physical or emotional problems, limitations in social activities due to physical or emotional problems, limitations in usual role activities due to physical or emotional problems, bodily pain, general mental health, vitality (energy and fatigue), and general health perception. In embodiments, the SF12 or SF36 survey is scored from 0 (worst health) to 100 (best health). In embodiments, the SF12 or SF36 score is increased after treatment with a composition provided herein. In embodiments, the SF12 or SF36 survey may include assessing a subject in need thereof administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's score is improved compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof.

[0097] In embodiments, SF12 or SF36 assessment for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, The administration may be evaluated at 1 week, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, SF12 or SF36 assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0098] Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form 7a (Fatigue) In embodiments, the assessment includes the PROMIS Fatigue 7a survey. The PROMIS Fatigue 7a survey may assess a range of self-reported symptoms, from mild subjective fatigue to overwhelming, debilitating, and persistent fatigue. In embodiments, fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and its impact on physical, mental, and social activities. In embodiments, the PROMIS Fatigue 7a survey assesses symptoms over the past week. In embodiments, the PROMIS Fatigue 7a survey assesses symptoms over the past week. The study can include evaluating a subject in need thereof who has been administered the anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's self-reported symptoms are improved compared to an otherwise equivalent procedure in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0099] In embodiments, the PROMIS Fatigue 7a rating for an anti-CD19 antibody or antigen-binding fragment thereof is measured at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days The administration may be evaluated at 1 week, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, the PROMIS Fatigue 7a rating for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0100] PROMIS Short Form 8a In embodiments, the assessment includes the PROMIS Pain Interference 8a Survey. The PROMIS Pain Interference 8a Survey can assess the impact of pain on a subject's life. The PROMIS Pain Interference 8a Survey can include the extent to which pain interferes with engagement in social, cognitive, emotional, physical, and recreational activities. In embodiments, the PROMIS Pain Interference 8a Survey can include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's pain interference is improved compared to an otherwise equivalent procedure in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0101] In embodiments, the PROMIS Short Form 8a assessment for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, 56 weeks, 57 weeks, 58 weeks, 59 weeks, 60 weeks, 61 weeks, 62 weeks, 63 weeks, 64 weeks, 65 weeks, 66 weeks, The evaluation can be performed at 4 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, PROMIS short form 8a assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0102] PROMIS Short Form 8b In embodiments, the assessment includes the PROMIS Physical Function 8b survey. The surveys may assess various self-reported abilities. The PROMIS Physical Function 8b survey may include a subject's upper extremity (e.g., dexterity), lower extremity (e.g., walking or mobility), and central region (e.g., neck and back) function, as well as daily activities (e.g., running errands). In embodiments, the PROMIS Physical Function 8b survey may include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's self-reported ability is improved compared to an otherwise equivalent procedure in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0103] In embodiments, the PROMIS Physical Function 8b assessment for the anti-CD19 antibody or antigen-binding fragment thereof is administered at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, The administration of the compound can be evaluated at 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, the PROMIS Physical Function 8b assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0104] Handheld Dynamometry In embodiments, the assessment includes handheld dynamometry. In embodiments, handheld dynamometry has been shown to have high reliability, construct validity, and responsiveness in myositis patients (Saygin et al., 2021), particularly the ability to assess the strength of a single muscle group (Baschung et al., 2018). Handheld dynamometry can be used to assess muscle strength. In embodiments, handheld dynamometry assessments can assess the strength of a single muscle group at a time. In embodiments, handheld dynamometry assessments of subjects administered an anti-CD19 antibody or antigen-binding fragment thereof are determined relative to baseline. In embodiments, the subject's score is improved relative to an otherwise equivalent method in which the subject is not administered an anti-CD19 antibody or antigen-binding fragment thereof.

[0105] In embodiments, handheld dynamometry assessment of the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, or 12 weeks prior to initiation of treatment. The administration of the compound can be evaluated at 142 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, handheld dynamometry assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at approximately day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment. It can be evaluated as follows.

[0106] Patient Global Impression of Severity (PGIS) survey In embodiments, the assessment includes a PGIS survey. The PGIS survey can ask the subject how much their myopathy has changed using a categorical scale. In embodiments, the PGIS survey can be administered to a subject in need thereof after administering an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. In embodiments, the PGIS survey score is at least about 1, about 2, about 3, about 4, or about 5. In embodiments, the PGIS survey scale can range from 1 (very good) to 5 (very poor). In embodiments, the PGIS survey level is reduced by at least about 1, about 2, about 3, or about 4 points after treatment with a composition provided herein. In embodiments, the PGIS survey can include evaluating a subject in need thereof administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0107] In embodiments, PGIS assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks prior to initiation of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, PGIS assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0108] Patient Global Impression of Change (PGIC) survey In embodiments, the evaluation includes a PGIC survey. The PGIC survey can ask the subject how much their myopathy has changed using a categorical scale. In embodiments, the PGIC survey can be performed after a subject in need thereof is administered an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. In embodiments, the PGIC survey score is at least about 1, about 2, about 3, about 4, or about 5. In embodiments, the PGIC survey scale can range from 1 (very good) to 5 (very poor). In embodiments, the PGIC survey level is reduced by at least about 1, about 2, about 3, or about 4 points after treatment with a composition provided herein. In embodiments, the PGIC survey can include evaluating a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0109] In embodiments, PGIC assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, 67 days, The administration of the compound can be evaluated at 142 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, PGIC assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0110] Clinical Global Impression of Severity (CGIC) survey In embodiments, the evaluation includes a CGIC survey. The CGIC survey may use a categorical scale to determine how much a subject's health has changed. In embodiments, the CGIC survey may evaluate a subject's cognitive, functional, or behavioral status, or a combination thereof. In embodiments, the CGIC survey may be administered to a clinician monitoring a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. In embodiments, the CGIC survey score is at least about 1, about 2, about 3, about 4, about 5, about 6, or about 7. In embodiments, the CGIC survey scale may range from 1 (normal) to 7 (among the most severely affected patients). In embodiments, the CGIC survey level is reduced by at least about 1, about 2, about 3, about 4, about 5, or about 6 points after treatment with a composition provided herein. In embodiments, the CGIC survey may comprise evaluating a clinician monitoring a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's clinician score is decreased compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof.

[0111] In embodiments, CGIC assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks prior to initiation of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, CGIC assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0112] Myositis Functional Index (FI3) Survey In embodiments, the assessment includes a Myositis FI3 assessment. The Myositis FI3 assessment can be used to assess the functional outcome of muscle endurance and function in frequently affected muscle groups (MFI3 2016). In embodiments, the Myositis FI3 assessment is scored on a scale of about 1, 2, 3, 4, 5, 6, 7, 8, 9, up to about 10. In embodiments, the Myositis FI3 assessment is scored on a scale of about 0-10, about 1-5, about 4-10, or about 1-10. In embodiments, the Myositis FI3 score ranges from 0 (no exercise) to 10 (maximum exercise). In embodiments, the Myositis FI3 assessment is scored as the number of repetitions correctly performed at a maximum of 60 or 120 repetitions, depending on the muscle group being assessed. In embodiments, the Myositis FI3 assessment is scored on a scale of about 1, 2, 3, 4, 5, 6, 7, 8, 9, up to about 10. The method can include assessing a subject in need thereof who has been administered the anti-CD19 antibody or antigen-binding fragment thereof as compared to a baseline. In an embodiment, the myositis FI3 score is reduced as compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0113] In embodiments, the Myositis FI3 assessment for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks prior to initiation of treatment. The administration of the compound can be evaluated at 12 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, the Myositis FI3 assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0114] 24-hour general pain numerical rating scale (NRS) In embodiments, the assessment includes a 24-hour general pain NRS. The 24-hour general pain NRS can assess the intensity of pain a subject may have experienced within the past 24 hours. In embodiments, the 24-hour general pain NRS ranges from about 1, 2, 3, 4, 5, 6, 7, 8, 9, and up to about 10. In some embodiments, the 24-hour general pain NRS is about 0-5, about 0-10, or about 1-10. The 24-hour general pain NRS can range from 0 (no pain) to 10 (worst pain imaginable). In embodiments, the 24-hour general pain NRS can include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0115] In aspects, the 24-hour global pain NRS rating for the anti-CD19 antibody or antigen-binding fragment thereof is measured at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days The administration of the compound can be evaluated at 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, the 24-hour global pain NRS rating for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0116] 5-Level 5Q-5D (EQ-5D-5L) In embodiments, the assessment includes an EQ-5D-5L survey. The EQ-5D-5L survey assesses mobility. The EQ-5D-5L survey may be used to assess mood, self-care, daily activities, pain discomfort, or anxiety / depression, and combinations thereof. In embodiments, the EQ-5D-5L survey may be administered to a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. In embodiments, the EQ-5D-5L survey is scored using a visual analog scale (VAS). In embodiments, the EQ-5D-5L survey score is at least about 1, about 2, about 3, about 4, or about 5. In embodiments, the EQ-5D-5L survey scale may range from 1 (best) to 5 (worst). In embodiments, the EQ-5D-5L survey level is reduced by at least about 1, about 2, about 3, or about 4 points after treatment with a composition provided herein. In embodiments, the EQ-5D-5L survey may include assessing a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to baseline. In embodiments, the subject's score is decreased compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof.

[0117] In embodiments, the EQ-5D-5L assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, The administration of the compound can be evaluated at 142 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, EQ-5D-5L assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 12 ± 7 days, week 26 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 46 ± 7 days after initiation of treatment.

[0118] Muscle-related enzymes In some embodiments, the evaluation includes measuring muscle-associated enzyme levels. Muscle-associated enzymes evaluated can include, but are not limited to, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and aldolase, and combinations thereof. In embodiments, CK is evaluated. In embodiments, whole blood, plasma, serum, and urine are collected to evaluate muscle-associated enzyme levels. In embodiments, evaluating muscle-associated enzyme levels can include evaluating a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In aspects, administration of an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure increases the level of a muscle-associated enzyme in a subject by at least about or at most about 10%, 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to ... in In embodiments, administration of an anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure is effective to reduce muscle-associated enzyme levels in a subject by at least about, or at most about, 3% to 5%, 5% to 10%, 10% to 20%, 5% to 25%, 20 to 40%, 30 to 50%, 40 to 60%, 45 to 75%, 60 to 80%, 75 to 95%, or 80 to 100%, compared to baseline levels before administration.

[0119] In some embodiments, assessment of muscle-associated enzymes in response to an anti-CD19 antibody or antigen-binding fragment thereof is performed at about days -28, -27, -26, -25, -24, -23, -28, -29, -30, -31, -32, -33, -34, -35, -36, -37, -38, -39, -40, -41, -42, -43, -44, - 2 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks The administration of the compound can be evaluated at 142 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In aspects, assessment of muscle-associated enzymes for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about day -28, day -27, day -26, day -25, day -24, day -23, day -22, day -21, day -20, day -19, day -18, day -17, day -16, day -15, day -14, day -13, day -12, day -11, day -10 from the start of treatment. , day −9, day −8, day −7, day −6, day −5, day −4, day −3, day −2, day −1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 22 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, week 42 ± 7 days, week 46 ± 7 days, and week 52 ± 7 days.

[0120] Pharmacokinetic evaluation In embodiments, the methods provided herein may include determining the concentration of an anti-CD19 antibody or antigen-binding fragment thereof in a subject in need thereof after administration. In embodiments, the methods include a pharmacokinetic assessment. In embodiments, the sample is a blood sample or a plasma sample, or a combination of both. In embodiments, suitable assays for measuring pharmacokinetics may include electrochemiluminescence (ECL) assays, bead-based assays, cell-based assays, and combinations thereof. In embodiments, the sample may include plasma, wherein the plasma is assayed for peak concentration (C max ), area under the concentration-time curve (AUC), clearance (CL), and terminal elimination half-life (T1 / 2) are measured for anti-CD19 antibodies or antigen-binding fragments thereof.

[0121] In embodiments, pharmacokinetic assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks from the start of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In aspects, pharmacokinetic assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about day −28, day −27, day −26, day −25, day −24, day −23, day −22, day −21, day −20, day −19, day −18, day −17, day −16, day −15, day −14, day −13, day −12, day −11, day −10, day −9, day −8, day −7, day −6, day −5, day −4, day −3, day −2, day −1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 5 ± 7 days after initiation of treatment. Evaluation can be performed at week 2 ± 7 days.

[0122] immunogenicity In embodiments, the evaluation includes determining the level of immunogenicity, if any, of the anti-CD19 antibody or antigen-binding fragment thereof of the present disclosure. Immunogenicity includes determining the status and / or titer of anti-drug antibodies (ADA) against the anti-CD19 antibody or antigen-binding fragment thereof. The presence of ADA can be assessed using plasma samples from subjects administered the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, ADA is not detectable after administration of the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, ADA levels are reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof, e.g., compared to ADA levels in an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof. Approximately 1 0%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or maximum in It's a 100% decrease.

[0123] In embodiments, immunogenicity assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks prior to initiation of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, assessment of immunogenicity to an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day −28, day −27, day −26, day −25, day −24, day −23, day −22, day −21, day −20, day −19, day −18, day −17, day −16, day −15, day −14, day −13, day −12, day −11, day −10, day −9, day −8, day −7, day −6, day −5, day −4, day −3, day −2, day −1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, and week 52 ± 7 days from the start of treatment.

[0124] Transcriptomics In embodiments, the evaluation involves quantifying the expression levels of genes or gene pathways associated with disease activity by whole blood transcriptomics. In embodiments, whole blood transcriptomics can be evaluated by RNA isolation from whole blood. In embodiments, RNA testing can be performed to evaluate changes in the expression of genes or gene pathways associated with myositis over time, the mechanism of action of or in response to administration of an anti-CD19 antibody or antigen-binding fragment thereof, or the etiology of myositis.

[0125] RNA may be isolated from whole blood at baseline to test for changes in the expression levels of genes or gene pathways associated with disease activity. In embodiments, transcriptome profiling is assessed by methods including, but not limited to, qPCR, RNAseq, and exome sequencing.

[0126] In embodiments, expression levels of genes associated with disease activity by RNA analysis are measured in subjects after administration. is at least about 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 40-fold, 60-fold, 80-fold, 100-fold, 120-fold, 140-fold, 160-fold, 180-fold, 200-fold, 220-fold, 240-fold, 260-fold, 280-fold, or up to ... in In embodiments, the expression levels of genes associated with disease activity by RNA analysis may be reduced by at least about 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100-fold, compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof. in It can be reduced by 100%.

[0127] In embodiments, transcriptomic analysis for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, 67 days, The administration may be evaluated at 1 week, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, transcriptomic analysis for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about day 1, week 6 ± 7 days, week 12 ± 7 days, week 26 ± 3 days, week 30 ± 7 days, week 34 ± 7 days, week 38 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, week 104 ± 7 days, and week 116 ± 7 days after initiation of treatment.

[0128] Whole Blood for DNA, SNP, and Epigenetic Analysis In some embodiments, the evaluation involves determining the sequence of genes associated with disease activity by whole blood DNA analysis. In embodiments, DNA testing can be performed to assess changes over time in the sequence of genes, including: single nucleotide polymorphisms (SNPs) associated with the occurrence of myositis (e.g., IMNM) genes that may be related to the mechanism of action of an anti-CD19 antibody or antigen-binding fragment thereof.

[0129] In some embodiments, whole blood can be collected and used to evaluate gene sequences before, during, and after treatment with any of the compositions provided herein. Gene sequences found to be regulated by treatment can be analyzed in whole blood using quantitative methods. Samples can be used to examine gene sequences and their changes over time, as assessed by NGS, Sanger sequencing, or PCR.

[0130] In aspects, determining gene sequence changes associated with disease activity and / or treatment effect by DNA analysis of the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, or less after initiation of treatment. ,-3 days,-2 days,-1 day,0 days,1 day,2 days,3 days,4 days,5 days,6 days,1 week,2 weeks,3 weeks,4 weeks,5 weeks,6 weeks,7 weeks,8 weeks,9 weeks,10 weeks,11 weeks,12 weeks,13 weeks,14 weeks,15 weeks,16 weeks,17 weeks,18 weeks,19 weeks,20 weeks,21 weeks,22 weeks,23 weeks,24 weeks,25 weeks,26 weeks,27 weeks,28 weeks,29 weeks,30 weeks,31 weeks,32 weeks,33 weeks,34 weeks,35 weeks, The treatment can be evaluated at 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about week 142. In embodiments, determining gene sequence changes associated with disease activity and / or therapeutic efficacy by DNA analysis for the anti-CD19 antibody or antigen-binding fragment thereof can be evaluated at about day 1, week 6 ± 7 days, week 12 ± 7 days, week 26 ± 3 days, week 38 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, week 104 ± 7 days, and week 116 ± 7 days after treatment initiation.

[0131] Pharmacodynamic evaluation In embodiments, the method includes a pharmacodynamic assessment. In embodiments, the assessment can be performed over a period of time. In embodiments, the sample includes a blood sample, a serum sample, a plasma sample, or a muscle sample. In embodiments, the muscle biopsy location can be identified by MRI. In embodiments, the muscle biopsy can be performed by non-invasive surgery (e.g., needle biopsy) or invasive surgery (i.e., open biopsy). Assays suitable for assessing biomarker levels can include flow cytometry, histology, immunohistochemistry, blood analysis, microscopy, PCR, ELISA, and combinations thereof.

[0132] In embodiments, the methods provided herein can include determining levels of biomarkers, including but not limited to, SPR, HMGCR, total Ig, IgA, IgM, IgG, CD19+ cells (e.g., CD19+ B cells), CD20+ cells (e.g., CD20 plasmablasts, CD20 plasma cells), and peripheral blood mononuclear cells (PBMCs, e.g., T cells, B cells), after administration of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof. Exemplary B cells include, but are not limited to, circulating B cells, blood B cells, splenic B cells, marginal zone B cells, follicular B cells, peritoneal B cells, bone marrow B cells, precursor B cells, early pro-B cells, late pro-B cells, large pre-B cells, small pre-B cells, immature B cells, mature B cells, antigen-stimulated B cells, and / or plasma cells. In embodiments, a decrease in a biomarker can be detected compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, loss of biomarkers can be detected compared to an otherwise equivalent method in which the subject is not administered an anti-CD19 antibody or antigen-binding fragment thereof, compared to an otherwise equivalent method lacking administration of an anti-CD19 antibody or antigen-binding fragment thereof, In embodiments, the decrease in biomarkers is at least about or at most about 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40-fold, 45-fold, 50-fold, 55-fold, 60-fold, 65-fold, 70-fold, 75-fold, 80-fold, 85-fold, 90-fold, 95-fold, 100-fold, 105-fold compared to an otherwise equivalent method lacking administration. , 110x, 115x, 120x, 125x, 130x, 135x, 140x, 145x, 150x, 155x, 160x, 165x, 170x, 175x, 180x, 185x, 19x, 195x, 200x, 210x, 220x, 230x, 240x, 250x, 260x, 270x, 280x, 290x, or maximum in In embodiments, the effectiveness of administration of an anti-CD19 antibody or antigen-binding fragment thereof on a biomarker can be assessed over time using a suitable immunoassay. In embodiments, the effect of an anti-CD19 antibody or antigen-binding fragment thereof is assessed over time using a certified immunoassay.

[0133] The present disclosure provides compositions containing anti-CD19 antibodies that effectively reduce or deplete B cells in a subject. The anti-CD19 antibodies or antigen-binding fragments thereof bind to and deplete biomarkers, so that the reduction or elimination can be used as a measure of therapeutic efficacy. In embodiments, total B cells are a measure of target binding.

[0134] In embodiments, the anti-CD19 antibody or antigen-binding fragment thereof is administered to a subject in a manner that improves the immune response by at least about 100% compared to an otherwise equivalent method in which the subject is not administered the anti-CD19 antibody or antigen-binding fragment thereof. 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or maximum inA reduction of about 100% in B cell levels can be achieved. Reduction or elimination of SPR, HMGCR, total Ig, IgA, IgM, IgG, CD19+ cells (e.g., CD19+ B cells), CD20+ cells (e.g., CD20 plasmablasts, CD20 plasma cells), and peripheral blood mononuclear cells (PBMCs, e.g., B cells), or a combination thereof, can be sustained over an extended period of time. In embodiments, SPR, HMGCR, total Ig, IgA, IgM, IgG, CD19+ cells (e.g., CD19+ B cells), CD20+ cells (e.g., CD20 plasmablasts, CD20 plasma cells), and peripheral blood mononuclear cells (PBMCs, e.g., B cells), or combinations thereof, may persist for at least 1 day, at least 2 days, at least 3 days, at least 7 days, at least 8 days, at least 9 days, at least 4 days, at least 5 days, at least 6 days, at least 10 days, at least 15 days, at least 20 days, at least 25 days, or at least 30 days. In embodiments, the SPR, HMGCR, total Ig, IgA, IgM, IgG, CD19+ cells (e.g., CD19+ B cells), CD20+ cells (e.g., CD20 plasmablasts, CD20 plasma cells), and peripheral blood mononuclear cells (PBMCs, e.g., B cells), or combinations thereof, may persist for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 9 weeks, at least 7 weeks, at least 8 weeks, at least 6 weeks, or at least 10 weeks. In embodiments, SPR, HMGCR, total Ig, IgA, IgM, IgG, CD19+ cells (e.g., CD19+ B cells), CD20+ cells (e.g., CD20 plasmablasts, CD20 plasma cells), and peripheral blood mononuclear cells (PBMCs, e.g., B cells), or a combination thereof, may persist for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 9 months, at least 7 months, at least 8 months, at least 6 months, at least 10 months, at least 11 months, or at least 12 months.

[0135] In embodiments, pharmacodynamic assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks from the start of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In aspects, pharmacodynamic assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about day −28, day −27, day −26, day −25, day −24, day −23, day −22, day −21, day −20, day −19, day −18, day −17, day −16, day −15, day −14, day −13, day −12, day −11, day −10, day −9, day −8, day −7 from the start of treatment. , day -6, day -5, day -4, day -3, day -2, day -1, day 0, day 1, week 2 ± 3 days, week 6 ± 7 days, week 12 ± 7 days, week 18 ± 7 days, week 22 ± 7 days, week 26 ± 3 days, week 30 ± 3 days, week 34 ± 7 days, week 38 ± 7 days, week 42 ± 7 days, week 46 ± 7 days, week 52 ± 7 days, week 78 ± 7 days, week 104 ± 7 days, and week 116 ± 7 days.

[0136] Open Label Period (OLP) Eligibility In embodiments, the evaluation includes determining the eligibility of the subject to enroll in an OLP, also known as an open-label extension (OLE). Evaluations, including determining whether the elephant has previously received the anti-CD19 antigen-binding fragment, may include completion of Phase 2 or Phase 3, discontinuation of any non-B cell depleting / non-GC immunomodulatory agents, or planning for tapering of any GCs, or a combination thereof.

[0137] In embodiments, assessments determining a subject's eligibility to enroll in the OLP are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1, 2, 3 days, 4, 5, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks prior to initiation of treatment. , 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks.

[0138] In embodiments, assessments to determine a subject's eligibility to enroll in the OLP may be assessed at about day 1, week 26 ± 3 days, and week 52 ± 7 days after initiation of treatment.

[0139] Health Assessment Questionnaire-Disability Index (HAQ-DI) In embodiments, the assessment includes the HAQ-DI, which assesses the physical function of a subject in need thereof (HAQ-DI Form 05a). In embodiments, the HAQ-DI is scored at about 0, 1, 2, or a maximum of inA score of about 3 may be assigned. In embodiments, the HAQ-DI score is at least about 0, about 1, about 2, or about 3. In embodiments, the HAQ-DI may include the following eight sections: dressing and grooming, getting up, eating, walking, hygiene, reaching, grasping, and general daily activities. In embodiments, each section is scored from 0 (without any difficulty) to 3 (unable to do). In embodiments, the HAQ-DI assessment may include evaluating a subject in need thereof who has been administered an anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's HAQ-DI score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0140] In embodiments, the HAQ-DI assessment for an anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks prior to the start of treatment. The administration of the compound can be evaluated at 12 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, HAQ-DI assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about week 26 ± 3 days and week 52 ± 7 days after initiation of treatment.

[0141] Patient Global Assessment (PGA) of Disease Activity In some embodiments, the assessment includes a patient global assessment (PGA) of disease activity. The PGA is used to assess the The patient's global assessment of overall disease activity is measured. In embodiments, the PGA rating is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 2 in The PGA score is scored on a scale of about 0 to 10, about 1 to 5, about 4 to 10, or about 1 to 10. In embodiments, the PGA may be measured using a 10 cm visual analog scale (VAS) ranging from "no evidence of disease activity" to "very active or severe disease activity." In embodiments, the PGA assessment may comprise assessing a subject in need thereof who has been administered the anti-CD19 antibody or antigen-binding fragment thereof compared to a baseline. In embodiments, the subject's PGA score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody or antigen-binding fragment thereof.

[0142] In embodiments, PGA assessments for the anti-CD19 antibody or antigen-binding fragment thereof are performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, 42 days, 43 days, 44 days, 45 days, 46 days, 47 days, 48 ​​days, 49 days, 50 days, 51 days, 52 days, 53 days, 54 days, 55 days, 56 days, 56 days, 57 days, 58 days, 59 days, 60 days, 61 days, 62 days, 63 days, 64 days, 65 days, 66 days, The administration may be evaluated at 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, PGA assessments for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about 26 weeks ± 3 days and 52 weeks ± 7 days after initiation of treatment.

[0143] Composite Glucocorticoid Toxicity Index (CGTI) In embodiments, the evaluation includes a CGTI study. In embodiments, the CGTI study evaluates the morbidity and GC-sparing ability of glucocorticoid (GC)-related treatment after treatment initiation. In embodiments, the CGTI study includes assessment of body mass index (BMI), glucose tolerance, blood pressure, lipids, bone mineral density, steroid myopathy, skin toxicity, neuropsychiatric toxicity, infection, gastrointestinal, musculoskeletal, and ocular. In embodiments, a subject in need thereof has been administered a CD19 antibody or antigen-binding fragment thereof and is evaluated for CGTI. In embodiments, the CGTI is about -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 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, 110, 111, 112, 113, 114, 115, 116, 117, 118 5, 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, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 1 13, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159 , 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206 6, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264 , 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366 23, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381 1, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, or maximum inA score of about 439 is assigned. In embodiments, the CGTI study can include evaluating a subject in need thereof who has been administered the anti-CD19 antibody, or antigen-binding fragment thereof, compared to a baseline. In embodiments, the subject's CGTI score is reduced compared to an otherwise equivalent method in which the subject does not receive the anti-CD19 antibody, or antigen-binding fragment thereof.

[0144] In embodiments, CGTI assessment for the anti-CD19 antibody or antigen-binding fragment thereof is performed at about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks prior to initiation of treatment. , 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 78 weeks, 104 weeks, or at least about 142 weeks. In embodiments, CGTI assessment for an anti-CD19 antibody or antigen-binding fragment thereof can be assessed at about week 26 ± 3 days and week 52 ± 7 days after initiation of treatment.

[0145] Pharmaceutical Composition In an aspect, a pharmaceutical composition is provided. In an aspect, a therapeutic regimen comprising the pharmaceutical composition is also provided.

[0146] The pharmaceutical composition may comprise an anti-CD19 antibody or antigen-binding fragment thereof. In embodiments, the pharmaceutical composition comprises an anti-CD19 antibody or antigen-binding fragment thereof and a compound provided herein. and one or more additional therapeutic agents. In embodiments, the one or more additional therapeutic agents may include a corticosteroid, an analgesic, or an immunomodulatory agent, or a combination thereof.

[0147] Many drugs can be administered orally as liquids, capsules, tablets, or chewable tablets. The oral route is the most convenient, usually the safest, and least expensive, and therefore the most frequently used. However, it has limitations due to the way drugs typically move through the digestive tract. For orally administered drugs, absorption may begin in the mouth and stomach. However, most drugs are typically absorbed from the small intestine. Drugs pass through the intestinal wall and travel to the liver, and are then transported to their target site via the bloodstream. The intestinal wall and liver chemically alter (metabolize) many drugs, reducing the amount of drug that reaches the bloodstream. As a result, these drugs are often administered in smaller doses when injected intravenously to achieve the same effect.

[0148] In the subcutaneous route, a needle is inserted into the fatty tissue just below the skin. After the drug (e.g., an anti-CD19 antibody or its antigen-binding fragment) is injected, it travels into small blood vessels (capillaries) and is carried by the bloodstream. Alternatively, the drug reaches the bloodstream through lymphatic vessels. The intramuscular route is preferred over the subcutaneous route when larger amounts of medication are needed. A longer needle is used because the muscle is beneath the skin and fatty tissue. Drugs are usually injected into the abdominal, upper arm, thigh, or buttock muscles. The rate at which a drug is absorbed into the bloodstream depends in part on the blood supply to the muscle. The smaller the blood supply, the more time it takes for the drug to be absorbed. In the intravenous route, a needle is inserted directly into a vein. The drug-containing solution may be given as a single dose or by continuous infusion. With infusion, the solution moves by gravity (from a collapsible plastic bag) or, more commonly, by an infusion pump through thin, flexible tubing into a tube (catheter) inserted into a vein, usually in the forearm.

[0149] In embodiments, the pharmaceutical compositions provided herein are administered by infusion. The infusion can occur over a period of time. For example, the infusion can be administration of the pharmaceutical agent over a period of about 5 minutes to about 10 hours. The infusion can last for about 5 minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, or up to about 10 hours. in It may be administered over a period of about 10 hours. In embodiments, intravenous administration is used to deliver a precise dose systemically in a rapid and well-controlled manner. When given by subcutaneous or intramuscular injection, irritating solutions that cause pain and tissue damage are also used. When given intravenously, the drug is delivered immediately to the bloodstream and tends to take effect more quickly than when given by other routes. Before each IV infusion, the subject may receive prophylaxis with IV methylprednisone, oral diphenhydramine, and oral acetaminophen, or equivalents, to reduce the risk or severity of a potential reaction. In embodiments, the methylprednisolone dosage may range from about 10 mg to about 300 mg, about 20 mg to about 200 mg, about 30 mg to about 150 mg, about 40 mg to about 100 mg, about 50 mg to about 150 mg, or about 75 mg to about 125 mg. In an embodiment, the methylprednisolone dose can be about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 120 mg, 140 mg, 160 mg, 180 mg, 200 mg, 225 mg, 250 mg, 275 mg, or 300 mg. In an embodiment, the methylprednisolone dose can be about 100 mg. In an embodiment, the oral diphenhydramine dose can be in the range of about 5 mg to about 250 mg, about 10 mg to about 200 mg, about 15 mg to about 100 mg, about 20 mg to about 70 mg, about 25 mg to about 50 mg, about 15 mg to about 50 mg, or about 25 mg to about 60 mg. In an embodiment, the oral diphenhydramine dose can be in the range of about 25 mg to about 50 mg. In embodiments, the oral acetaminophen dose is from about 10 mg to about In an embodiment, the oral acetaminophen dose can range from about 500 to about 650 mg.

[0150] In some embodiments, the medication is administered intrathecally. In the intrathecal route, a needle is inserted between two vertebrae in the lower spine and into the space around the spinal cord. The medication is then injected into the spinal canal. A small amount of local anesthetic is often used to anesthetize the injection site. This route is used when a medication needs to act quickly or locally on the brain, spinal cord, or the layers of tissue covering them (meninges), for example, to treat infections in these structures.

[0151] Medications administered by inhalation through the mouth can be atomized into smaller droplets than those administered via the nasal route, allowing the medication to pass through the trachea (bronchi) and enter the lungs. How deeply the droplets penetrate the lungs depends on their size. Smaller droplets penetrate deeper, which increases the amount of medication absorbed. Once inside the lungs, they are absorbed into the bloodstream. Medications applied to the skin are typically used for their local effects and are therefore most commonly used to treat superficial skin disorders such as psoriasis, eczema, skin infections (viral, bacterial, and fungal), itching, and dry skin. The medication is mixed with an inactive substance. Depending on the consistency of the inactive substance, the formulation can be an ointment, cream, lotion, solution, powder, or gel.

[0152] In some embodiments, the therapeutic regimen comprising the pharmaceutical composition may be administered according to the subject's body weight. For subjects who are determined to be obese (BMI>35), it may be necessary to use the actual body weight. In some embodiments, the dosage may be calculated using body surface area.

[0153] In some embodiments, the pharmaceutical composition can be administered by any route, alone or together with a pharmaceutically acceptable carrier or excipient, and such administration can be carried out in both single and multiple doses. More specifically, the pharmaceutical composition can be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hand candies, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Such carriers include solid diluents or fillers, sterile aqueous media, and various non-toxic organic solvents. Furthermore, the pharmaceutical formulations can be suitably sweetened and / or flavored with various agents of the type commonly used for such purposes. Exemplary carriers and excipients include dextrose, sodium chloride (NaCl), sucrose, lactose, cellulose, xylitol, sorbitol, maltitol, gelatin, PEG, PVP, histidine / histidine hydrochloride, trehalose dihydrate, polysorbate 80, and any combination thereof. In embodiments, the excipients include histidine / histidine hydrochloride, NaCl, trehalose dihydrate, and polysorbate 80.

[0154] Various compositions and methods utilizing the same are provided. In embodiments, the compositions of the present disclosure are used in methods of treating a human subject. In embodiments, the subject in need thereof is a child (birth to 18 years of age). In embodiments, the pediatric subject in need thereof is between about birth and about 5 years of age, between birth and about 4 years of age, between about 3 and about 10 years of age, between about 5 and about 12 years of age, between about 7 and about 18 years of age, between about 10 and about 18 years of age, between about 14 and about 18 years of age, or between about 16 and about 18 years of age. In embodiments, the pediatric subject is at least about 16 years of age. In embodiments, the pediatric subject is between about 16 and about 18 years of age. In embodiments, the pediatric subject is between about 10 and 18 years of age, between 12 and 18 years of age, between 14 and 18 years of age, between 16 and 18 years of age, between 17 and 18 years of age, or between birth and 18 years of age.

[0155] Numbered Embodiments Notwithstanding the appended claims, the following numbered embodiments also form part of this disclosure.

[0156] Embodiment Set A 1. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8.

[0157] 2. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, and the subject in need thereof is a child.

[0158] 3. The method of embodiment 2, wherein the pediatric subject is 16 to 18 years of age.

[0159] 4. The method of any one of embodiments 1 to 3, wherein the subject is signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody positive (HMGCR-Ab+), or both SRP-Ab+ and HMGCR-Ab+.

[0160] 5. The method of embodiment 4, wherein the subject is SRP-Ab+.

[0161] 6. The method of embodiment 4, wherein the subject is HMGCR-Ab+.

[0162] 7. The method of any one of embodiments 1-3, wherein the subject is signal recognition particle-antibody negative (SRP-Ab-), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody negative (HMGCR-Ab-), or both SRP-Ab- and HMGCR-Ab-.

[0163] 8. The method of any one of embodiments 1-7, wherein the subject in need thereof has previously been treated with conventional therapy.

[0164] 9. The method of embodiment 8, wherein the conventional therapy comprises corticosteroids, nonsteroidal immunosuppressants (ISTs), antibody therapy, or any combination thereof.

[0165] 10. The method of embodiment 9, wherein the conventional treatment is a corticosteroid, and the corticosteroid is prednisone.

[0166] 11. The method of embodiment 9, wherein the conventional therapy is an IST selected from the group consisting of methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and any combination thereof.

[0167] 12. Conventional treatments include rituximab, ocrelizumab, obinutuzumab, and ofatum 10. The method of embodiment 9, wherein the antibody therapy is selected from the group consisting of mab, inebilizumab intravenous immunoglobulin (IVIg), and combinations thereof.

[0168] 13. The method of any one of embodiments 8 to 12, wherein the conventional therapy is tapered after administration of an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof.

[0169] 14. The method of embodiment 13, wherein tapering comprises decreasing the dosage of the conventional therapy every two weeks starting at week 26.

[0170] 15. The method of embodiment 13 or 14, wherein the conventional therapy comprises prednisone, and the prednisone is tapered by 5 mg every two weeks after administration.

[0171] 16. The method of embodiment 15, wherein the tapering continues through at least week 12.

[0172] 17. The method of any one of embodiments 4-16, wherein the subject has been determined to have at least one of SRP-Ab or HMGCR-Ab prior to administration.

[0173] 18. The method of any one of embodiments 1 to 17, wherein the administration of the anti-CD19 antibody or antigen-binding fragment thereof is repeated.

[0174] 19. The method of any one of embodiments 1-17, wherein administration is repeated at 2, 26, 52, 78, 104, 130, and 156 weeks.

[0175] 20. The method of any one of embodiments 1-19, wherein the administration, repeated administration, or both, is effective to alleviate the disease or its symptoms by 12, 26, or 52 weeks.

[0176] 21. Administration, repeated administration, or both, is associated with an increase in the 2016 ACR / EULAR Total Improvement Score (TIS). Decision 20. The method of any one of embodiments 1 to 19, wherein the method is effective to reduce the disease or symptoms thereof by 26 weeks after administration, when determined to be effective in reducing the disease or symptoms thereof, as compared to the subject's baseline score or the score of an untreated subject.

[0177] 22. Dosing, repeat dosing, or both, does not increase the subject's baseline level or levels of treatment-naïve of 20. The method of any one of embodiments 1-19, wherein the method is effective to reduce the disease or a symptom thereof by 26 weeks after administration, relative to the level in the subject.

[0178] 23. The method of embodiment 22, wherein the alleviation of the disease or its symptoms is determined by improvement in muscle weakness, reduction in serum CK levels, reduction in atrophy, reduction in edema, reduction in fatty tissue replacement, reduction in interstitial lung disease, reduction in B-cell levels, MMT8 score, and combinations thereof.

[0179] 24. The method of any one of embodiments 1 to 23, wherein the subject is a human.

[0180] 25. The method of any one of embodiments 21-23, wherein the disease reduction is at least about 3-fold, 5-fold, 20-fold, 40-fold, 60-fold, 80-fold, or up to about 100-fold.

[0181] 26. The method of any one of embodiments 21 to 23, wherein the TIS score is ≧5, 10, 20, 30, 40, 50, 60, 80, or 100.

[0182] 27. The method of any one of embodiments 1-26, wherein a glucocorticoid, an antihistamine, an analgesic, and any combination thereof is administered prophylactically prior to administration to a subject in need thereof.

[0183] 28. The method of embodiment 27, wherein the subject is prophylactically administered a glucocorticoid, an antihistamine, and an analgesic.

[0184] 29. The method of any one of embodiments 1-26, wherein the subject is administered prophylactically methylprednisolone, diphenhydramine, and acetaminophen.

[0185] 30. The method of any one of embodiments 1 to 29, wherein the effective amount of the anti-CD19 antibody or antigen-binding fragment thereof is about 50 mg to 1000 mg, 100 to 800 mg, 200 to 600 mg, 200 to 500 mg, 250 to 450 mg, 200 to 350 mg, 250 to 350 mg, or 375 to 325 mg.

[0186] 31. The method of any one of embodiments 1-29, wherein the effective amount is about 50 mg, 100 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

[0187] 32. The method of embodiment 31, wherein the effective amount is about 300 mg.

[0188] 33. The method of any one of embodiments 1 to 32, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0189] 34. The method of any one of embodiments 1 to 33, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0190] 35. The method of any one of embodiments 1 to 34, wherein the anti-CD19 antibody is a monoclonal antibody.

[0191] 36. The method of any one of embodiments 1 to 35, wherein the anti-CD19 antibody is defucosylated.

[0192] 37. The method of any one of embodiments 18-36, wherein the administration, repeated administration, or both, is effective to eliminate IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0193] 38. The method of any one of embodiments 18-37, wherein the administration, repeated administration, or both, is effective to stabilize or alleviate IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0194] 39. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising the step of administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is approximately 100 mg to 1000 mg.

[0195] 40. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of an anti- A method comprising administering to a subject in need thereof an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8, respectively, and wherein the effective amount is approximately 300 mg.

[0196] 41. A method of treatment, comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a pediatric subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively.

[0197] 42. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of inebilizumab to a subject in need thereof, wherein the effective amount is between about 100 mg and 1000 mg.

[0198] 43. A method of treatment, comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is positive for an autoantibody selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0199] 44. A method of treatment, comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is negative for autoantibodies selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0200] 45. The method of any one of embodiments 1-44, wherein administration comprises 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof on days 1 and 15, followed by one 300 mg injection approximately every six months thereafter.

[0201] Embodiment Set B 1. An anti-CD19 antibody or antigen-binding fragment thereof for use in the treatment of immune-mediated necrotizing myopathy (IMNM), comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8.

[0202] 2. An anti-CD19 antibody or antigen-binding fragment thereof for use in the treatment of immune-mediated necrotizing myopathy (IMNM) in a pediatric subject, comprising the complementarity-determining region (CDR): An anti-CD19 antibody or antigen-binding fragment thereof comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8.

[0203] 3. The use of embodiment 2, wherein the pediatric subject is 16 to 18 years of age.

[0204] 4. The use of any one of embodiments 1 to 3, wherein the subject is signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody positive (HMGCR-Ab+), or both SRP-Ab+ and HMGCR-Ab+.

[0205] 5. The use of embodiment 4, wherein the subject is SRP-Ab+.

[0206] 6. The use of embodiment 4, wherein the subject is HMGCR-Ab+.

[0207] 7. The use of any one of embodiments 1 to 3, wherein the subject is signal recognition particle-antibody negative (SRP-Ab-), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody negative (HMGCR-Ab-), or both SRP-Ab- and HMGCR-Ab-.

[0208] 8. The use of any one of embodiments 1 to 7, wherein the subject in need thereof has previously been treated with conventional therapy.

[0209] 9. The use of embodiment 8, wherein the conventional therapy comprises corticosteroids, nonsteroidal immunosuppressants (ISTs), antibody therapy, or any combination thereof.

[0210] 10. The use according to embodiment 9, wherein the conventional treatment is a corticosteroid, and the corticosteroid is prednisone.

[0211] 11. The use of embodiment 9, wherein the conventional therapy is an IST selected from the group consisting of methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and any combination thereof.

[0212] 12. The use of embodiment 9, wherein the conventional therapy is an antibody therapy selected from the group consisting of rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab intravenous immunoglobulin (IVIg), and combinations thereof.

[0213] 13. The use of any one of embodiments 8 to 12, wherein the conventional therapy is tapered after administration of an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof.

[0214] 14. The use of embodiment 13, wherein tapering comprises reducing the dosage of conventional therapy every two weeks starting at week 26.

[0215] 15. The use according to embodiment 13 or 14, wherein the conventional therapy comprises prednisone, which is tapered by 5 mg every two weeks after administration.

[0216] 16. The use of embodiment 15, wherein the tapering continues until at least week 12.

[0217] 17. The use according to any one of embodiments 4 to 16, wherein the subject has been determined to have at least one of SRP-Ab or HMGCR-Ab prior to administration.

[0218] 18. The use according to any one of embodiments 1 to 17, wherein the administration of the anti-CD19 antibody or antigen-binding fragment thereof is repeated.

[0219] 19. The use according to any one of embodiments 1 to 17, wherein administration is repeated at 2, 26, 52, 78, 104, 130 and 156 weeks.

[0220] 20. The use of any one of embodiments 1-19, wherein the administration, repeated administration, or both, is effective in alleviating the disease or its symptoms by 12, 26, or 52 weeks.

[0221] 21. Administration, repeated administration, or both, is associated with an increase in the 2016 ACR / EULAR Total Improvement Score (TIS). Decision 20. The use of any one of embodiments 1 to 19, wherein the use is effective to reduce the disease or symptoms thereof by 26 weeks after administration, when measured against a baseline score of the subject or a score of an untreated subject.

[0222] 22. Dosing, repeat dosing, or both, does not increase the subject's baseline level or levels of treatment-naïve of 20. The use of any one of embodiments 1 to 19, which is effective in reducing the disease or symptoms thereof by 26 weeks after administration, relative to levels in the subject.

[0223] 23. The use of embodiment 22, wherein the alleviation of the disease or its symptoms is determined by improvement in muscle weakness, reduction in serum CK levels, reduction in atrophy, reduction in edema, reduction in fatty tissue replacement, reduction in interstitial lung disease, reduction in B-cell levels, MMT8 score, and combinations thereof.

[0224] 24. The use according to any one of embodiments 1 to 23, wherein the subject is a human.

[0225] 25. The use according to any one of embodiments 21 to 23, wherein the reduction in disease is at least about 3-fold, 5-fold, 20-fold, 40-fold, 60-fold, 80-fold, or up to about 100-fold.

[0226] 26. The use according to any one of embodiments 21 to 23, wherein the TIS score is ≧5, 10, 20, 30, 40, 50, 60, 80, or 100.

[0227] 27. The use according to any one of embodiments 1 to 26, wherein the glucocorticoid, antihistamine, analgesic, and any combination thereof are administered prophylactically prior to administration to a subject in need thereof.

[0228] 28. The use of embodiment 27, wherein the subject is administered prophylactically a glucocorticoid, an antihistamine, and an analgesic.

[0229] 29. The use of any one of embodiments 1-26, wherein the subject is administered prophylactically methylprednisolone, diphenhydramine, and acetaminophen.

[0230] 30. The use of any one of embodiments 1 to 29, wherein the effective amount of the anti-CD19 antibody or antigen-binding fragment thereof is about 50 mg to 1000 mg, 100 to 800 mg, 200 to 600 mg, 200 to 500 mg, 250 to 450 mg, 200 to 350 mg, 250 to 350 mg, or 375 to 325 mg.

[0231] 31. Effective doses are approximately 50 mg, 100 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, and 500 mg. , 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

[0232] 32. The use according to embodiment 31, wherein the effective amount is about 300 mg.

[0233] 33. The use according to any one of embodiments 1 to 32, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0234] 34. The use according to any one of embodiments 1 to 32, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0235] 35. The use according to any one of embodiments 1 to 34, wherein the anti-CD19 antibody is a monoclonal antibody.

[0236] 36. The method of any one of embodiments 1 to 35, wherein the anti-CD19 antibody is defucosylated.

[0237] 37. The use of any one of embodiments 18-36, wherein the administration, repeated administration, or both, is effective to eliminate IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0238] 38. The use of any one of embodiments 18-37, wherein the administration, repeated administration, or both, is effective to stabilize or alleviate IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

[0239] 39. An anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM), comprising complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, wherein approximately 100 mg to 1000 mg of the anti-CD19 antibody or antigen-binding fragment thereof is administered to a subject in need thereof.

[0240] 40. An anti-CD19 antibody or antigen-binding fragment thereof for use in treating immune-mediated necrotizing myopathy (IMNM), comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, wherein approximately 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof is administered to a subject in need thereof.

[0241] 41. An anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells in a pediatric subject, the anti-CD19 antibody or antigen-binding fragment thereof comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8, respectively.

[0242] 42. Inebilizumab for use in the treatment of immune-mediated necrotizing myopathy (IMNM), wherein about 100 mg to 1000 mg of inebilizumab is administered to a subject in need thereof.

[0243] 43. An anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells, comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8, respectively, and wherein the subject is positive for an autoantibody selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0244] 44. An anti-CD19 antibody or antigen-binding fragment thereof for use in treating a disease associated with CD19-expressing cells, comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7 and 8, respectively, and the subject is negative for autoantibodies selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and both SRP and HMGCR.

[0245] 45. The use of any one of embodiments 1-44, wherein administration comprises 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof on days 1 and 15, followed by one 300 mg injection approximately every 6 months thereafter.

[0246] 46. ​​An anti-CD19 antibody or antigen-binding fragment thereof for use in the treatment of immune-mediated necrotizing myopathy (IMNM), comprising complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and wherein approximately 300 mg is administered every 6 months, with an initial dose of 300 mg administered two weeks before the first 300 mg dose every 6 months.

[0247] 47. The use of any one of embodiments 38 to 46, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

[0248] 48. The use according to any one of embodiments 38 to 46, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively. [Example]

[0249] Example 1 - A Phase 2 / 3 Randomized, Double-Blind, Placebo-Controlled Study with Open-Label Extension to Evaluate the Efficacy and Safety of Inebilizumab in Adults and Adolescents Aged 16 Years and Older with Immune-Mediated Necrotizing Myopathy Disclosed herein is an open-label, Phase 2 / 3, randomized, double-blind, placebo-controlled efficacy and safety study of inebilizumab in adults and adolescents aged 16 years and older with immune-mediated necrotizing myopathy (IMNM).

[0250] Objectives and Endpoints The study objectives and endpoints are presented below and, unless otherwise specified, are identical for Phases 2 and 3, with independent analyses of the two populations.

[0251] The primary objective is to evaluate whether inebilizumab can improve overall IMNM disease activity, as measured by the Total Improvement Score (TIS).

[0252] Secondary Objectives To evaluate the safety and tolerability of inebilizumab in subjects with IMNM To evaluate the effect of inebilizumab on other measures of disease activity To characterize the pharmacokinetic (PK) and immunogenicity profile of inebilizumab in IMNM. To evaluate whether inebilizumab can reduce corticosteroid burden.

[0253] exploratory purpose To characterize the pharmacodynamic (PD) profile of inebilizumab and its effects on disease biomarkers. To assess whether inebilizumab can improve overall IMNM disease activity as measured by muscle biopsy and MRI. To evaluate the effect of inebilizumab on each antibody subtype. To evaluate whether inebilizumab can prevent the use of rescue therapy or reduce the incidence of clinical deterioration. To assess the effect of inebilizumab on functional health and mobility in patients with IMNM.To assess the effect of inebilizumab on quality of life, utilization of healthcare resources, and well-being from the patient's perspective. To evaluate whether inebilizumab can improve IMNM-associated interstitial lung disease (ILD).

[0254] Primary endpoint 1. The primary efficacy endpoint for both studies was the mean 2016 ACR / EULAR Total Improvement Score (TIS) at 26 weeks.

[0255] Key Secondary Endpoints 1. The proportion of participants at week 26 who achieve a ≥ 40 point improvement in TIS during the Randomized Controlled Period (RCP) and are not receiving rescue therapy after week 8. 2. Proportion of participants with an MMT-8 improvement of 8% or greater at week 26 who are not receiving rescue therapy after week 8 during RCP. 3. Median change from baseline in creatine kinase (CK) muscle levels at week 26. 4. Proportion of participants who achieve key secondary endpoint 1, key secondary endpoint 2, and achieve a 50% reduction in CK levels from baseline at week 26.

[0256] Secondary endpoints 1. The proportion of participants at week 26 who achieve a ≥ 20-point improvement in TIS during RCP and are not receiving rescue therapy after week 8. 2. The proportion of participants at week 26 who achieve a ≥ 30-point improvement in TIS during RCP and are not receiving rescue therapy after week 8. 3. The proportion of participants at week 26 who achieve a ≥ 50-point improvement in TIS during RCP and are not receiving rescue therapy after week 8. 4. The proportion of participants at week 26 who achieve a ≥ 60-point improvement in TIS during RCP and are not receiving rescue therapy after week 8. 5. Change from baseline in Patient Global Assessment (PGA) of Disease Activity at Week 26 of Phase 2 and Week 52 of Phase 3. 6. Change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 26 of Phase 2 and Week 52 of Phase 3. 7. Change from baseline in steroid dose to the final visit at Week 26 of Phase 2 and Week 52 of Phase 3. 8. Percentage of participants who taper their corticosteroid dose to 7.5 mg / day (or 50% reduction) during RCP and are free of rescue therapy after 8 weeks. 9. Proportion of participants who achieve normal or near normal CK levels and are not receiving rescue therapy after 8 weeks during RCP. 10. Proportion of participants with a ≥10% improvement in MMT-8 at week 26 and no rescue therapy after week 8 during RCP. 11. Change from baseline in individual TIS Core Set measures at week 26 in participants who did not receive rescue therapy after week 8 during the RCP. 12. Change from baseline in proximal MMT at week 26 in participants who did not receive rescue therapy after week 8 during the RCP. 13. Change from baseline in extramuscular global assessment at Week 26 of Phase 2 and Week 52 of Phase 3. 14. A Lewis acid screen was performed under: Change from baseline in abbreviated handheld dynamometry at week 26 of Phase 2 and week 52 of Phase 3. 15. Change from baseline in Patient Global Impression of Severity (PGI-S) at Week 26 of Phase 2 and Week 52 of Phase 3. 16. Patient Global Impression of Change (PGI-C) at Week 26 of Phase 2 and Week 52 of Phase 3. 17. Change from baseline in Clinical Global Impression of Severity (CGI-S) at Week 26 in Phase 2 and Week 52 in Phase 3. 18. Change from baseline in Clinical Global Impression of Change (CGI-C) at Week 26 in Phase 2 and Week 52 in Phase 3. 19. Change from baseline in Myositis Function Index (FI-3) at Week 26 of Phase 2 and Week 52 of Phase 3. 20. Change from baseline in Patient-Reported Outcomes Information System (PROMIS) Pain Interference 8a v1.0 at Week 26 of Phase 2 and Week 52 of Phase 3. 21. Change from baseline in the Numerical Rating Scale (NRS) for pain, assessing worst pain in the past 7 days, at Week 26 of Phase 2 and Week 52 of Phase 3. 22. Mean TIS at week 26, independently for SRP-Ab+ and HMGCR-Ab+ subtypes.

[0257] For both studies: Exploratory endpoints 1. Changes in anti-SRP and anti-HMGCR antibody titers. 2. Changes in B and T cell flow cytometry (CD20+ B cell counts) and immune cell subset phenotyping. 3. Changes in exploratory endpoints related to disease or mechanism of action (blood gene expression profiles, serum / plasma biomarkers). 4. Effect of genetic markers on the mechanism of action of inebilizumab. 5. Proportion of participants who did not receive rescue therapy after 8 weeks during the RCP. Total cases received salvage therapy after 6.8 weeks. 7. Time to first protocol-defined clinical deterioration during RCP. 8. Change from baseline using disease-specific MRI results (optional subtest) . 9. Change from baseline using pre- and post-treatment muscle biopsies (optional subtest). 10. Key secondary endpoints for SRP-Ab+ and HMGCR-Ab+ subtypes will be evaluated independently. 11. Change from baseline in Extramuscular Activity Core Set Scales in SRP-Ab+ participants. 12. Change from baseline in PFTs in participants with interstitial lung disease (ILD). 13. Change from baseline in PROMIS Short Form 7a (fatigue). 14. Change in Fatigue NRS, which assesses worst physical fatigue over the past 7 days [Timeframe: Phase 2: up to 24 weeks; Phase 3: up to 52 weeks]. 15. Change from baseline in PROMIS Short Form 8a (pain interference). 16. Change from baseline in PROMIS Short Form 8b (physical function). 17. Change from baseline on the Short Form-12. 18. Change in the 36-item Short Form Survey version 2 (SF-36v2) physical function subscale and physical component summary scores at week 26 of Phase 2 and week 52 of Phase 3. 19. Composite Glucocorticoid Toxicity Index (C-GTI) at week 26 of Phase 2 and week 52 of Phase 3. 20. Change from baseline in EQ-5D-5L utility at Week 26 in Phase 2 and Week 52 in Phase 3. 21. Change from baseline in EQ-5D-5L VAS at Week 26 of Phase 2 and Week 52 of Phase 3. 22. Change from baseline in the Timed Get Up and Go Test at Week 26 of Phase 2 and Week 52 of Phase 3. 23. Change from baseline in the 2-minute walk test at week 26 of Phase 2 and week 52 of Phase 3.

[0258] Both studies: other endpoints 1. Pharmacokinetic (PK) profile of inebilizumab over time. 2. Anti-drug antibody (ADA) status and titer over time.

[0259] Study design This study is a phase 2 / 3, randomized, double-blind, placebo-controlled trial. The target population is adult subjects ≥ 16 years of age with signal recognition particle-antibody positive (SRP-Ab+) or 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody positive (HMGCR-Ab+) immune-mediated necrotizing myopathy (IMNM). Within this single study, there are two separate phases. In each phase, subjects who complete the respective randomized controlled phase of the trial may be eligible for an additional 2-year open-label extension (OLE) phase. 1. Study 1: Phase 2, Proof of Concept (POC) 26-week Randomized Controlled Period (RCP) 2. Study 2: Phase 3, 52-week RCP

[0260] Approximately 170 adult subjects (40 in the Phase 2 study and 130 in the Phase 3 study) will be enrolled. Both pools of subjects will be randomized 1:1 to receive either inebilizumab or placebo. Subjects will be randomized 1:1 to minimize the risk of baseline imbalance between treatment groups. The study will be stratified by autoantibody type (SRP-Ab+ vs. HMGCR-Ab+). For Phase I, a minimum of 10 SRP-Ab+ and 10 HMGCR-Ab+ participants will be enrolled in each stratum. For Phase II, a minimum of 20 SRP-Ab+ and 20 HMGCR-Ab+ participants will be enrolled in each stratum. An overview of the study design is shown in Figures 1 and 2, and details of study activities are provided in the evaluation schedule (Table 2) and Tables 3 and 4.

[0261] [Table 2]

[0262] [Table 3-1]

[0263] [Table 3-2]

[0264] [Table 4-1]

[0265] [Table 4-2]

[0266] [Table 4-3]

[0267] During Phase 2, participants enrolled in the corticosteroid trial will maintain a stable dose of corticosteroids throughout the treatment period. During Phase 3, participants will follow a corticosteroid tapering protocol outlined below (Table 5). In Phase 3, steroid tapering will not occur until after the 26-week time point.

[0268] [Table 5]

[0269] Subjects participating in a phase 3 corticosteroid trial may begin corticosteroid tapering according to protocol after week 26 of the RCP, with the goal that all participants will reach 7.5 mg / day or a 50% reduction in corticosteroid dose by week 35 (Table 5). Participants will maintain this stable dose until the end of the RCP.

[0270] Clinical deterioration (both trials) Participants may be evaluated for a Clinical Exacerbation Visit if clinical deterioration occurs. Protocol-defined clinical deterioration includes the following criteria: 1. In the opinion of the investigator, the participant's health is at risk, as evidenced by an elevation in creatine kinase (CK) or a significant worsening of the Global Improvement Score (TIS) rating, as defined below: A doubling of baseline CK levels b. 20-point worsening of TIS

[0271] All subjects planned to receive rescue therapy must meet criterion 1 plus (a) or (b). In addition, if protocol-defined clinical deterioration is confirmed, the sponsor must be contacted urgently.

[0272] Study population The following eligibility criteria apply to both Phase 2 and Phase 3 trials:

[0273] Selection Criteria Participants are eligible to participate in the study if they meet the following criteria: 1. Adults and young people aged 16 years or older and under 80 years old. 2. A prior diagnosis of IMNM, defined as a positive serological test for anti-SRP or anti-HMGCR antibodies within the past 5 years, which will be centrally confirmed. 3. Clinical evidence of active disease, defined as achieving both of the following: a.CK>1000U / L b. Score of ≤136 units on the MMT-8 4. Subjects may enter the study with the following baseline medications: a. There is no specific treatment for the disease b. Prednisone or its equivalent (≤ 20 (or 15) mg / day) with stable dosing for at least 2 weeks prior to screening and continued stability prior to randomization c. Nonsteroidal IST with at least 12 weeks of treatment duration with at least 8 weeks of stable dosing prior to screening and continued stability prior to randomization: i. Methotrexate ii. Azathioprine iii. Mycophenolate mofetil iv. Mycophenolic acid v. Tacrolimus vi. Cyclosporine 5. Women of childbearing potential who are sexually active with an uncontraceptively administered male partner must use at least one highly effective method of contraception (Table 6) from the time of screening through 6 months after the last dose of investigational drug (IP). Periodic abstinence, rhythm methods, and withdrawal methods are not acceptable methods of contraception. a. Note: A woman of childbearing potential is defined as one who has not been surgically sterilized (i.e., bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or is not postmenopausal (defined as 12 months without menstruation without other medical cause and a follicle-stimulating hormone [FSH] level in the postmenopausal range [≥ 16.70 mIU / mL]). If an amenorrheal subject's FSH level is not in the postmenopausal range, she may still enroll in the study but must follow the same contraceptive requirements as women of childbearing potential.

[0274] [Table 6]

[0275] 6. Uncontraceptively protected men who are sexually active with a female partner of childbearing potential must use condoms from Day 1 of the study period through 3 months after the last dose of investigational drug (IP). Because male condoms are not a highly effective method of contraception, it is strongly recommended that female partners of male study subjects also use a highly effective method of contraception throughout this period (Table 6).

[0276] Exclusion criteria Participants are ineligible for study participation if they meet any of the following criteria:

[0277] Key exclusion criteria 1. Any condition that, in the opinion of the investigator, places the participant at unacceptable risk of complications, interferes with the evaluation of the IP, or confounds the participant's safety or the interpretation of the study results. 2. Women who are breastfeeding or pregnant, or who plan to become pregnant any time during the RCP after signing the Informed Consent Form (ICF) and within 6 months after the last IP dose. 3. Spontaneous or induced abortion, stillbirth, or live birth within the 4 weeks prior to screening. 4. Weight < 37.5 kg. 5. History of drug or alcohol abuse within one year prior to screening, or any condition determined by the investigator to be non-compliant. 6. History of severe allergic or anaphylactic reaction to biologic agents or known allergy to any component of the IP formulation. 7. History of significant recurrent infection (e.g., requiring hospitalization or intravenous [IV] antibiotics). 8. Clinically significant active infection requiring antimicrobial agents within 2 weeks prior to the screening visit (but tolerate chronic nail infection). 9. History of cancer except for the following: a.Appears to have been successfully treated with curative therapy >12 months prior to screening in situ carcinoma of the cervix. b. Basal or squamous cell carcinoma of the skin that has undergone curative treatment for more than 12 months prior to screening and has been apparently successfully treated. c. Prostate cancer treated with radical prostatectomy or radiation therapy with curative intent for more than 3 years prior to screening and with no known recurrence or current treatment. 10. Any of the following laboratory abnormalities at screening (one repeat test may be performed to confirm the result prior to randomization within the same screening period): Elevated liver enzymes (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x upper limit of normal (ULN) unless due to underlying disease of IMNM with investigator and medical monitor approval) b. Total bilirubin >1.5 × ULN (except in cases due to Gilbert syndrome) c. Estimated glomerular filtration rate (eGFR) < 45 mL / min / 1.73 m 2 d.CD19+B cell count <40 cells / μL e. Absolute neutrophil count (ANC) < 1.2 x 10 3 cells / μL f. Platelet count <75,000 / μL (or <75×10 9 / L) g. Hemoglobin < 8.0 g / dL h. Total Ig < 600 mg / dL 11. Known immunodeficiency disorder, including current infection or positive test for human immunodeficiency virus (HIV). 12. Positive test for chronic hepatitis B infection at screening, defined as (1) hepatitis B surface antigen (HBsAg) positive or (2) hepatitis B core antibody (anti-HBc) positive + hepatitis B surface antibody (anti-HBs) negative. a. Note: Subjects with positive anti-HBs only, or positive anti-HBc + positive anti-HBs, and negative HbsAg are eligible for enrollment. 13. Hepatitis C virus antibody test positive. 14. History of active or latent tuberculosis (TB) or a positive QuantiFERON®-TB GOLD test at screening (unless TB treatment has been completed according to local guidelines). Subjects with latent TB who are actively on anti-TB treatment or who test positive for QuantiFERON®-TB GOLD may be enrolled if they have completed at least one month of anti-TB treatment and intend to complete a full course of anti-TB treatment. Subjects with an indeterminate QuantiFERON®-TB GOLD test result may be enrolled if the QuantiFERON®-TB GOLD repeat test or tuberculin skin test is negative.

[0278] Disease-related exclusion criteria 15. Use of statin medication within 28 days prior to screening or anticipated use during the study (if HMGCR-Ab+). 16. Currently use a wheelchair or use a wheelchair on a daily basis. 17. Uncontrolled or rapidly progressing ILD. 18. History of clinically significant cardiac disease.

[0279] Previous and concomitant therapy exclusion criteria 19. Concurrent / prior enrollment in another clinical trial involving receipt of investigational treatment within 4 weeks or 5 half-lives of investigational treatment (whichever is longer) prior to screening. 20. Receipt of any biological B-cell depleting therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) or any experimental B-cell depleting agent in the 6 months prior to screening. 21. Received any other monoclonal antibody (mAb) or large molecule biologic, including but not limited to, FcRn inhibitors, anti-TNF mAb, anti-JAK Stat mAb, and complement inhibitors, within 3 months or 5 half-lives of treatment (whichever is longer) prior to screening. 22. Have received any of the following within 4 weeks prior to screening: a.IVIG b. Plasma exchange (PLEX) treatment. c. Live attenuated vaccines (administration of inactivated (killed) vaccines is acceptable). d. Blood transfusion.

[0280] Prohibited drugs The following medications and procedures are not permitted during the study: 1. Live attenuated vaccines. Commonly used live vaccines include Zostavax ( ® herpes zoster (shingles) vaccine; intranasal influenza vaccine; measles, mumps, rubella vaccine; rotavirus vaccine; oral typhoid vaccine; yellow fever vaccine; smallpox vaccine; and adenovirus vaccine. 2. IVIG or plasma exchange is limited to rescue therapy for protocol-defined clinical deterioration. 3. Any introduction or dose escalation of corticosteroids will be limited to rescue therapy for protocol-defined clinical deterioration. 4. Statin medication (if HMGCR-Ab+). 5. Any monoclonal antibody (mAb) or large molecule biologic, including but not limited to B cell depleting mAb, FcRn inhibitor, anti-TNF mAb, anti-JAK Stat mAb, and complement inhibitor. 6. Other immunosuppressive or immunomodulatory medications unless agreed upon after consultation with the sponsor's medical monitor or already in use at the time of randomization.

[0281] Dosage regimen and route of administration For the treatment of IMNM, inebilizumab is administered as a 300 mg intravenous (IV) infusion on days 1 and 15, then every 6 months thereafter.

[0282] In this study, participants will receive an IV infusion of inebilizumab (300 mg) or placebo at the following times: For Phase 2 trials: Days 1, 15, and 26 For Phase 3 trials: Day 1, Day 15, Week 26, and Week 52

[0283] All participants entering the OLE will receive an IV infusion of inebilizumab (300 mg) on ​​Day 1 of the OLE and every 6 months thereafter for 2 years. On Day 15 of the OLE, participants originally assigned to the inebilizumab arm of the RCP will receive placebo, while participants originally assigned to the placebo group will receive inebilizumab 300 mg IV on Day 15 to avoid unblinding of the initial participant's treatment assignment.

[0284] Prior to all IP infusions, all participants may be premedicated with prophylactic site-delivered IV methylprednisolone (100 mg or equivalent glucocorticoid), oral diphenhydramine (25-50 mg or equivalent antihistamine), and oral paracetamol (acetaminophen; 500-650 mg) to reduce the risk of infusion reactions.

[0285] Dosage form and strength Inebilizumab is a sterile liquid formulation (100 mg of inebilizumab per vial, 10 mL labeled volume) intended for IV infusion after dilution with saline.

[0286] Treatment and follow-up period Phase 2 The planned duration of the double-blind, randomized, controlled period is 26 weeks. The planned duration of the open-label extension period is 2 years.

[0287] Phase 3 The planned duration of the double-blind, randomized, controlled period is 52 weeks. The planned duration of the open-label extension period is 2 years.

[0288] Open Label Period (OLP) Eligibility To be eligible for OLP, a subject must: 1. Completed the RCP Week 26 visit (for Phase 2 clinical trials) or RCP Week 52 visit (for Phase 3 clinical trials). 2. Completed a 28-day washout period after discontinuation of non-B cell-depleting, non-GC immunosuppressive therapy initiated during RCP (if applicable). 3. Receive Dose 1 of OLP within 1-38 days after the RCP Week 26 (Phase 2) or Week 52 (Phase 3) visit (the final RCP visit and the first OLP visit cannot be on the same day). 4.If GC is administered at the time of OLP enrollment, the GC will be systematically tapered and discontinued within 8 weeks after administration of Dose 1 of OLP.

[0289] To maintain IP every 6 months, subjects may enroll in the OLP and receive it as soon as possible after completing the RCP.

[0290] Table 7 below summarizes the OLP procedural schedule for both studies.

[0291] [Table 7-1]

[0292] [Table 7-2]

[0293] [Table 7-3]

[0294] Evaluation criteria The 2016 ACR / EULAR Total Improvement Score (TIS) at 26 weeks of RCP will be used as the primary efficacy outcome measure. The TIS is based on the ACR / EULAR Board o The TIS is derived from standardized clinical response criteria developed and validated by the Directors for dermatomyositis (DM) and polymyositis (PM) (Aggarwal et al., 2017) and recommended for use as primary endpoints in myositis treatment trials. Improvement category thresholds for minimal, moderate, and major improvement have been developed and validated for DM and PM, but no specific thresholds have been developed for IMNM (Aggarwal et al., 2017). In the current design, a validation study of the TIS in IMNM will be conducted in conjunction with a Phase 2 trial. Participants in the validation study may be eligible for Phase 3 trials but not in Phase 2 trials. Therefore, a continuous outcome rather than a categorical outcome will be used for the primary endpoint. Continuous measurement may also provide greater power to detect change and provide greater sensitivity to change (Rider et al., 2018).

[0295] statistical analysis Phase 2 and Phase 3 analyses will be conducted separately. This section summarizes the statistical analyses planned for both phases unless otherwise stated. Further details will be provided in the overarching statistical analysis plan (SAP).

[0296] All Subjects Analysis Set This analysis set includes all subjects screened for the study and can be used for disposition reporting.

[0297] Complete Analysis Set The full analysis set (FAS) includes all randomized subjects who received at least one dose of IP in the study. Subjects can be analyzed according to their randomized treatment. Efficacy analysis is based on the FAS.

[0298] Pharmacokinetic (PK) Analysis Set The PK analysis set includes all subjects who received IP and had at least one quantifiable serum PK observation after the first dose. Subjects are analyzed according to the treatment they actually received. The PK analysis is based on the PK analysis set.

[0299] Any inebilizumab analysis set Any inebilizumab analysis set will include all subjects receiving any dose of inebilizumab.

[0300] Incorporation by Reference This patent application incorporates by reference in its entirety for all purposes the following patent publications and patent applications: International Application Nos. PCT / US2020 / 29613 and PCT / US2007 / 077916.

[0301] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, no reference, article, publication, patent, patent publication, or patent application cited herein is, and should not be, taken as an admission or any form of suggestion that it constitutes valid prior art or forms part of the common general knowledge anywhere in the world.

Claims

1. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising the step of administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8.

2. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, and the subject in need thereof is a child.

3. 3. The method of claim 2, wherein the pediatric subject is 16-18 years old.

4. 4. The method of any one of claims 1 to 3, wherein the subject is signal recognition particle-antibody positive (SRP-Ab+), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody positive (HMGCR-Ab+), or both SRP-Ab+ and HMGCR-Ab+.

5. The method of claim 4, wherein the subject is SRP-Ab+.

6. The method of claim 4, wherein the subject is HMGCR-Ab+.

7. 4. The method of any one of claims 1 to 3, wherein the subject is signal recognition particle-antibody negative (SRP-Ab-), 3-hydroxy-3-methylglutaryl coenzyme A reductase-antibody negative (HMGCR-Ab-), or both SRP-Ab- and HMGCR-Ab-.

8. The method of any one of claims 1 to 7, wherein the subject in need thereof has previously been treated with conventional therapy.

9. 9. The method of claim 8, wherein the conventional therapy comprises corticosteroids, nonsteroidal immunosuppressants (1STs), antibody therapy, or any combination thereof.

10. 10. The method of claim 9, wherein the conventional treatment is a corticosteroid, and the corticosteroid is prednisone.

11. 10. The method of claim 9, wherein the conventional therapy is an 1ST selected from the group consisting of methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, and any combination thereof.

12. 10. The method of claim 9, wherein the conventional therapy is an antibody therapy selected from the group consisting of rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab intravenous immunoglobulin (IVIg), and combinations thereof.

13. The method of any one of claims 8 to 12, wherein the conventional therapy is tapered after the administration of the effective amount of an anti-CD19 antibody or antigen-binding fragment thereof.

14. 14. The method of claim 13, wherein said tapering comprises decreasing the dosage of said conventional therapy every two weeks starting at week 26.

15. 15. The method of claim 13 or 14, wherein the conventional therapy comprises prednisone, and the prednisone is tapered by 5 mg every two weeks following the administration.

16. 16. The method of claim 15, wherein the tapering continues for at least 12 weeks.

17. The method of any one of claims 4 to 16, wherein the subject has been determined to have at least one of SRP-Ab or HMGCR-Ab prior to the administration.

18. The method of any one of claims 1 to 17, wherein the administration of the anti-CD19 antibody or antigen-binding fragment thereof is repeated.

19. 18. The method of any one of claims 1 to 17, wherein the administration is repeated at 2, 26, 52, 78, 104, 130 and 156 weeks.

20. 20. The method of any one of claims 1-19, wherein the administration, the repeated administration, or both, is effective to alleviate the disease or its symptoms by 12, 26, or 52 weeks.

21. 20. The method of any one of claims 1-19, wherein the administration, the repeated administration, or both, is effective in reducing the disease or symptoms thereof by 26 weeks after administration, as determined by an increase in the 2016 ACR / EULAR Total Improvement Score (TIS), compared to the subject's baseline score or the score of an untreated subject.

22. 20. The method of any one of claims 1-19, wherein the administration, the repeated administration, or both, is effective to reduce the disease or symptoms thereof by 26 weeks after administration, compared to the subject's baseline level or compared to levels in an untreated subject.

23. 23. The method of claim 22, wherein the alleviation of the disease or its symptoms is determined by improvement in muscle weakness, reduction in serum CK levels, reduction in atrophy, reduction in edema, reduction in fatty tissue replacement, reduction in interstitial lung disease, reduction in B cell levels, MMT8 score, and combinations thereof.

24. The method of any one of claims 1 to 23, wherein the subject is a human.

25. 24. The method of any one of claims 21-23, wherein the disease reduction is at least about 3-fold, 5-fold, 20-fold, 40-fold, 60-fold, 80-fold, or up to about 100-fold.

26. 24. The method of any one of claims 21 to 23, wherein the TIS score is >= 5, 10, 20, 30, 40, 50, 60, 80, or 100.

27. 27. The method of any one of claims 1 to 26, wherein a glucocorticoid, an antihistamine, an analgesic, and any combination thereof is administered prophylactically prior to said administration to a subject in need thereof.

28. 28. The method of claim 27, wherein the subject is administered the glucocorticoid, the antihistamine, and the analgesic prophylactically.

29. 27. The method of any one of claims 1 to 26, wherein the subject is administered prophylactically methylprednisolone, diphenhydramine, and acetaminophen.

30. 30. The method of any one of claims 1 to 29, wherein the effective amount of the anti-CD19 antibody or antigen-binding fragment thereof is about 50 mg to 1000 mg, 100 to 800 mg, 200 to 600 mg, 200 to 500 mg, 250 to 450 mg, 200 to 350 mg, 250 to 350 mg, or 375 to 325 mg.

31. 30. The method of any one of claims 1 to 29, wherein the effective amount is about 50 mg, 100 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

32. 32. The method of claim 31, wherein the effective amount is about 300 mg.

33. 33. The method of any one of claims 1 to 32, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region and the VL region comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

34. 33. The method of any one of claims 1 to 32, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region and the VL region comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

35. The method of any one of claims 1 to 34, wherein the anti-CD19 antibody is a monoclonal antibody.

36. The method of any one of claims 1 to 35, wherein the anti-CD19 antibody is defucosylated.

37. 37. The method of any one of claims 18-36, wherein the administration, the repeated administration, or both, is effective to clear the IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

38. 38. The method of any one of claims 18-37, wherein the administration, the repeated administration, or both, is effective to stabilize or alleviate the IMNM for at least about 3 months, 6 months, 1 year, or 2 years.

39. 1. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising: administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is between about 100 mg and 1000 mg.

40. A method for treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is approximately 300 mg.

41. A method of treatment, comprising administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a pediatric subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively.

42. 1. A method of treating immune-mediated necrotizing myopathy (IMNM), comprising administering an effective amount of inebilizumab to a subject in need thereof, wherein the effective amount is between about 100 mg and 1000 mg.

43. A method of treatment, comprising the step of administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is positive for an autoantibody selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and both SRP and HMGCR.

44. A method of treatment, comprising the step of administering an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the subject is negative for autoantibodies selected from the group consisting of signal recognition particle (SRP), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and both SRP and HMGCR.

45. 45. The method of any one of claims 1-44, wherein the administration comprises 300 mg of the anti-CD19 antibody or antigen-binding fragment thereof on days 1 and 15, and one 300 mg injection about every six months thereafter.

46. A method of treating immune-mediated necrotizing myopathy (IMNM), comprising administering to a subject in need thereof an effective amount of an anti-CD19 antibody or antigen-binding fragment thereof, wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises complementarity-determining regions (CDRs): HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2, 3, 4, 6, 7, and 8, respectively, and the effective amount is approximately 300 mg administered every six months, with an initial dose of 300 mg administered two weeks before the first 300 mg dose every six months.

47. 47. The method of any one of claims 38 to 46, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region and the VL region comprise amino acid sequences at least 80% identical to SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

48. 47. The method of any one of claims 38 to 46, wherein the anti-CD19 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region and the VL region comprise the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively.

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