Treating hidradenitis suppurativa with il-17 antagonist

Abstract

To provide a method for treating Hidradenitis Suppurativa (HS) using IL-17 antagonists, e.g., secukinumab.SOLUTION: Provided is a method for treating Hidradenitis Suppurativa (HS), the method comprising subcutaneously (SC) administering to a patient in need thereof a dose of about 300 mg to about 450 mg of an IL-17 antibody, or an antigen-binding fragment thereof, weekly during weeks 0, 1, 2, and 3.SELECTED DRAWING: None

Description

Technical Field

[0001] Cross - Reference to Related Applications This disclosure claims priority to U.S. Provisional Patent Application No. 62 / 588,687, filed on November 20, 2017, which is incorporated herein by reference in its entirety.

[0002] This disclosure relates to methods for treating hidradenitis suppurativa using IL - 17 antagonists, such as secukinumab.

Background Art

[0003] Hidradenitis suppurativa (HS) (also referred to as "acne inversa" or "Verneuil's disease") is a chronic, recurrent, and inflammatory disease characterized by deep nodules, sinus tracts, and abscesses that lead to fibrosis in the axilla, groin, inframammary crease, and anogenital regions (Revuz and Jemec (2016) Dermatol Clin 34:1 - 5; Jemec GB. (2012) N Engl J Med 366:158 - 64). This is associated with significant pain and comorbidities (including metabolic disorders, mental disorders, and autoimmune abnormalities), as well as an increased risk of skin cancer (Revuz (2016); Shlyankevich et al. (2014) J Am Acad Dermatol 71:1144 - 50; Kohorst et al. (2015) J Am Acad Dermatol 73:S27 - 35; Wolkenstein et al. (2007) J Am Acad Dermatol 56:621 - 3).

[0004] The reported prevalence of HS varies from <1% to 4% of the population (Shlyankev ich et al. (2014); Cosmatos et al. (2013) J Am Acad Dermatol 68:412-9; Davis et al. (2 015) Skin Appendage Disord 1:65-73; Revuz et al. (2008) J Am Acad Dermatol 59:596-60 1; McMillan K. (2014) Am J Epidemiol 179:14 77-83; Garg et al. (2017) JAMA Dermatol; Jem ec et al. (1996) J Am Acad Dermatol 35:191 -4). However, because HS is underdiagnosed, it is difficult to determine the true prevalence, and the estimated values vary with study design, population, and geographical location (Miller et al.( 2016) Dermatol Clin 34:7-16). The National Institutes of Health( (NIH) does not classify HS as a rare disease, but experts generally consider the prevalence of this disease to be <1% of the United States (US) population (Cosmatos et al . (2013); Genetic and Rare Diseases Inform ation Center. National Institutes of Heal th. Hidradenitis suppurativa. Available at : / / rarediseases.info.nih.gov / diseases / 66 58 / hidradenitis-suppurativa. Accessed Mar 5, 2018). Chapter 20, 2017; Gulliver et al. (2016) Rev Endo cr Metab Disord 17:343 - 51).

[0005] Current treatments for HS are topical and / or systemic antibiotics, hormonal interventions, analgesics, and , in certain cases, immunosuppressants, tumor necrosis factor [TNF] inhibitor monoclonal antibody adal imumab, and surgical excision (Gulliver et al. (2016); Z ouboulis et al. (2015) J Eur Acad Dermatol Venereol 29:619 - 4414 - 16; Kimball et al.( 2016) N Engl J Med 375:422 - 34). However, symptom control -l and lesion resolution are not consistent between treatments. The recurrence rate after discontinuation of antibiotic therapy is high, and long-term treatment with retinoids raises concerns about teratogenicity. Furthermore, the effectiveness of inflammatory drugs such as dapsone, fumaric acid esters , and cyclosporine is based on small case studies with variable results. As a result of these inconsistent outcomes and the severity of HS disease , HS patients utilize high-cost facility-based medical care (e.g., emergency departments and inpatient nursing) more frequently than patients with other chronic inflammatory skin conditions (Khalsa et al. (2016) J Am Acad Dermatol 73:609 - 14; Kirby et al. (2014) JAMA Dermatol 150:937 - 44). Since there is no medical cure for HS, this disease is physically and psychologically debilitating, and there remains a clear unmet need to provide a safe and effective long-term treatment for HS patients . (2016) J Am Acad Dermatol 73:609 - 14; Kirby et al. (2014) JAMA Dermatol 150:937 - 44). H S. There is a need for a medical treatment for HS that is physically and psychologically debilitating, and there remains a clear unmet need to provide a safe and effective long-term treatment for HS patients . SUMMARY OF THE INVENTION ​ [[Problems to be Solved by the Invention]]

[0006] The etiology of HS is not yet fully understood, but Van der Zee et a l. (2011) and Kelly et al. (2015) showed that the expressions of IL-17, IL-1 β, and TNF-α are enhanced in the lesional skin and the skin surrounding the lesions of HS patients and Matusiak et al. (2017) showed that patients with HS have an increase in the serum level of IL-17 compared to healthy volunteers, and the serum concentration of IL-17 in patients with more advanced diseases tends to be higher (Van der Zee et al. (2011) Br. Ass. Derm. 164 : 1292-1298 and Kelly et al. (2015) Br. J. Derma tol. 173(6): 1431-9; Matusiak et al. (2017) J . Am. Acad. Dermatol. 76(4): 670-675). Conversely, Bloc k et al. (2015) found that there is no significant difference in the serum concentrations of IL-2R, TNF -α, IL-17A, and IL-17F between HS patients and healthy controls and Banjeree et al. (2017) found that there is no significant difference in inflammatory cytokines such as TNF-α, IL-1β, IL-1α, IL-17A in HS wound exudates and specimens from chronic wound patients (Block et al. (2 015) Br. J. Dermatol. 174: 839-846; Banjeree e t al. (2017) Immunological Investigations 015) Br. J. Dermatol. 174: 839-846; Banjeree e t al. (2017) Immunological Investigations (46:149-158). Furthermore, during an open-label psoriasis study, the IL-17 antagonist, ixekizumab, induced three separate HS flares in the same patient (Gordon et al. (2014) J. Am. Acad. Dermatol. 71(6):1176- 82; Gordon et al. 72 Annu. Meet Am Acad D ermatol (AAD) (March 21-25, Denver) 2014, Ab nd st P7617). Thus, whether IL-17 dysregulation is causally related to HS pathogenesis (i.e., a driver of the disease) or simply represents the consequences of inflammation and / or injury caused by other triggers (i.e., a passenger of the disease) remains unclear. (i.e., a passenger of the disease) remains unclear.

[0007]

[0007] Secukinumab is a recombinant, high-affinity, fully human monoclonal IgG1 / κ anti-human interleukin-17A (IL-17A, IL-17) antibody. Secukinumab (see, e.g., WO 2006 / 013107 and WO 2007 / 117749) has a very high affinity for IL-17, i.e., a K of approximately 100-200 pM, and an IC of approximately 0.4 nM for neutralization of the biological activity of approximately 0.67 nM of human IL-17A in vitro. Thus, secukinumab inhibits the antigen in a molar ratio of approximately 1:1. This high binding affinity makes the secukinumab antibody particularly suitable for therapeutic use. Furthermore, secukinumab has a long half-life (i.e., approximately 4 weeks) that allows for an extended dosing interval, i.e., a highly desirable property for treating chronic lifelong disorders such as HS. D D of approximately 0.67 nM of human IL-17A in vitro. Thus, secukinumab inhibits the antigen in a molar ratio of approximately 1:1. This high binding affinity makes the secukinumab antibody particularly suitable for therapeutic use. Furthermore, secukinumab has a long half-life (i.e., approximately 4 weeks) that allows for an extended dosing interval, i.e., a highly desirable property for treating chronic lifelong disorders such as HS. 50 50 of approximately 1:1. This high binding affinity makes the secukinumab antibody particularly suitable for therapeutic use. Furthermore, secukinumab has a long half-life (i.e., approximately 4 weeks) that allows for an extended dosing interval, i.e., a highly desirable property for treating chronic lifelong disorders such as HS.

[0008] There are two case reports of secukinumab treatment in HS patients. Schuch et al .(2017) reported the treatment of severe refractory HS using secukinumab at a dose of 300 mg( SC) weekly for 1 month (days 0, 7, 14, 21, and 28), followed by injections at 4-week intervals (Schuch et al.(2017)Acta Derm V enereol.2018 Jan 12;98(1):151-152). Similarly, T horlacius et al.(2017) reported the treatment of HS patients with Hurley stage III lesions using 300 mg of sec ukinumab (SC) weekly for the first 4 weeks, then 300 mg (SC) at week 4 (Thorlacius et a l.(2017)Br.J.Dermatol doi:10.1111 / bjd.15 769.[Online edition ahead of print (Epub ahead of print)] ). However, in Thorlacius et al.(2017), the improvement in the number of tumors reported by patients, pain VAS, and pain / usefulness / handicap VAS was not fully reproduced by the scores reported by physicians, and the quality of life of patients after treatment initiation did not improve, as reflected by no change in the Dermatology Life Quality Index (DLQI) of patients with skin diseases . Furthermore, neither Schuch et al.(2017) nor Thorlacius et al.(20 17) reported whether the treatment used provided sustained response or whether the response was lost over time .

Means for Solving the Problems

[0009] The inventors herein have now devised a regimen for treating HS patients with secukinumab (and similar IL-17 antagonists, such as similar IL-17 antibodies or antigen-binding fragments thereof), which is highly effective and provides sustained response in HS patients. Disclosed herein is a method of treating HS, comprising administering subcutaneously (SC) to a patient in need thereof, during weeks 0, 1, 2, and 3, a dose of an IL-17 antibody or antigen-binding fragment thereof of from about 300 mg to about 450 mg per week, and thereafter a) starting during week 4, monthly (every 4 weeks); or b) starting during week 4, every other week (every 2 weeks) administering SC at a dose of from about 300 mg to about 450 mg. In some embodiments of the disclosed uses, methods, and kits, the IL-17 antagonist is an IL-17 antibody or antigen-binding fragment thereof. In some embodiments of the disclosed uses, methods, and kits, the IL-17 antibody or antigen-binding fragment thereof is selected from the group consisting of: a) an IL-17 antibody or antigen-binding fragment thereof that binds to an epitope of human IL-17 comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129; b) an IL-17 antibody or antigen-binding fragment thereof that binds to an epitope of human IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80; c) an epitope of an IL-17 homodimer having two mature human IL-17 protein chains (said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val1 on one chain

[0010] ​​​​​​​​​​​​​​24, Thr125, Pro126, Ile127, Val128, His129, and others (including Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain) binds to an IL-17 antibody or an antigen-binding fragment thereof; d) an epitope of an IL-17 homodimer having two mature human IL-17 protein chains (the epitope includes Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain) binds to an IL-17 antibody or an antigen-binding fragment thereof (wherein the IL-17 antibody or an antigen-binding fragment thereof has a K of about 100 - 200 pM and the IL-17 antibody or an antigen-binding fragment thereof has an in vivo half-life of about 23 to about 35 days); e) an epitope of an IL-17 homodimer having two mature IL-17 protein chains (the epitope includes Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain) binds to an IL-17 antibody (wherein the IL-17 antibody has a K of about 100 - 200 pM when measured by a biosensor system (e.g., BIACORE) and the IL-17 antibody has an in vivo half-life of about 23 D to about 30 days); and f) an IL-17 antibody or an antigen-binding fragment thereof comprising: i) an immunoglobulin heavy chain variable domain (V containing the amino acid sequence described as SEQ ID NO: 8 ; ii) an immunoglobulin light chain variable domain (V containing the amino acid sequence described as SEQ ID NO: 9 ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). D ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence). ; and iii) a hinge region, a CH2 domain, and a CH3 domain of an immunoglobulin heavy chain (the immunoglobulin heavy chain variable domain, immunoglobulin light chain variable domain, hinge region, CH2 domain, and CH3 domain are connected in sequence).H ii) the amino acid sequence set forth as SEQ ID NO:10 The immunoglobulin light chain variable domain (V L );iii) SEQ ID NO: 8 Immunoglobulin V containing the amino acid sequence H The domain and the amine depicted in SEQ ID NO: 10. Immunoglobulin V containing the .ALPHA. sequence L domain; iv) SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO: Immunoglobulin V containing the hypervariable region designated as number 3 H domain; v) sequence number 4, SEQ ID NO:5, and SEQ ID NO:6. L vi) the frequent domains depicted as SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13; Immunoglobulin V containing the variable region H domains; vii) SEQ ID NO:1, SEQ ID NO:2, and Immunoglobulin V containing the hypervariable region set forth as SEQ ID NO:3 H Domain and sequence number Immunoglobulins comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6. V L viii) the domains set forth as SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13; Immunoglobulin V containing a hypervariable region H Domain and SEQ ID NO: 4, SEQ ID NO: 5, and Immunoglobulin V containing the hypervariable region set forth as SEQ ID NO:6 L Domain;ix) distribution an immunoglobulin light chain comprising the amino acid sequence depicted as sequence number 14; or xi) an immunoglobulin heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 14. and an immunoglobulin light chain comprising the amino acid sequence set forth as SEQ ID NO: 15. Immunoglobulin heavy chain comprising the sequence. Some embodiments of the disclosed uses, methods, and kits In this case, the IL-17 antibody or its antigen-binding fragment is a human or humanized antibody. In some embodiments of the disclosed uses, methods, and kits, the IL-17 antibody or its antigen-binding fragment is secukinumab.

[0011] In a preferred embodiment, the IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab or its antigen-binding fragment) is administered subcutaneously (SC) at a dose of about 300 mg to about 450 mg, for example about 300 mg or about 450 mg (e.g., 300 mg or 450 mg). In some embodiments, the IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab or its antigen-binding fragment) is administered using an induction regimen followed by a maintenance regimen. In some embodiments, the induction regimen includes weekly administration, and the maintenance regimen includes administration every two weeks or every four weeks. In some embodiments, the IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab or its antigen-binding fragment) is administered SC at a dose of about 300 mg, for example 300 mg, at weeks 0, 1, 2, 3, and 4, and then every two weeks thereafter. In some embodiments, the IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab or its antigen-binding fragment) is administered SC at a dose of about 300 mg, for example 300 mg, at weeks 0, 1, 2, 3, and 4, and then every four weeks thereafter. In some embodiments, the IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab or its antigen-binding fragment) is administered SC at a dose of about 450 mg (e.g., 450 mg) every four weeks (monthly) at weeks 0, 1, 2, 3, and 4, and then thereafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0012]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 4

Figure 5

DETAILED DESCRIPTION OF THE INVENTION

[0013] As used herein, IL-17 refers to interleukin-17A (IL-17A) and means.

[0014] The term "comprising" encompasses "being included" as well as "consisting of". For example, a composition "comprising" X may consist solely of X or may include something additional (e.g., X + Y).

[0015] Unless otherwise specified or clear from the context, as used in this specification, the term "about" with respect to a numerical value is understood to be within the normal tolerance range in the art, e.g., within two standard deviations of the mean value. Thus, "about" can be within + / - 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.1%, 0.05 %, or 0.01% of the stated value, preferably + / - 10% of the stated value. When a numerical range or a list of numbers is used before the term "about", the term "about" applies to each number in the series. For example, the expression "about 1 - 5" should be interpreted as "about 1 - about 5", or for example, the expression "about 1, 2, 3, 4" should be interpreted as "about 1, about 2, about 3, about 4, etc.".

[0016] The word "substantially" does not exclude "completely". For example, a composition "substantially free of" Y The composition may not completely contain Y. Optionally, the word "substantially" can be omitted from the definition of the present disclosure. from the definition.

[0017] As used herein, the term "antibody" includes intact antibodies of natural origin. Antibodies of natural origin are glycoproteins comprising at least two heavy (H) chains interconnected by disulfide bonds and two light (L) chains. Each heavy chain consists of a heavy chain variable region (abbreviated herein as V H ) and a heavy chain constant region. The heavy chain constant region consists of three domains, CH1 , CH2 and CH3. Each light chain consists of a light chain variable region (abbreviated herein as V L ) and a light chain constant region. The light chain constant region consists of one domain, CL. V H and V L regions are interrupted by more conserved regions called framework regions (FR) and further subdivided into regions of high variability called hypervariable regions or complementarity-determining regions (CDRs). Each V and V H and V L consists of three CDRs and four FRs arranged in the following order from amino terminus to carboxy terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. Exemplary antibodies include secukinumab (Table 1), anti-XAB4 (U.S. Patent No. 9,193,788) and ixekizumab (U.S. Patent No. 7 cells) and the first component (C1q) of the classical complement system, to host tissues or factors. Exemplary antibodies include secukinumab (Table 1), brin. Exemplary antibodies include secukinumab (Table 1), anti-XAB4 (U.S. Patent No. 9,193,788) and ixekizumab (U.S. Patent No. 7 , Patent No. 838,638 (the entire content of the disclosure of which is incorporated by reference) may be mentioned.

[0018] As used herein, the term "antigen-binding fragment" of an antibody refers to a fragment of an antibody that retains the ability to specifically bind to an antigen (e.g., IL-17 ). It has been shown that the antigen-binding function of an antibody can be performed by fragments of the full-length antibody. The term "antigen-binding portion" of an antibody Examples of binding fragments included in include Fab fragments, i.e., V L , V H , CL and CH1 a monovalent fragment consisting of domains; F(ab)2 fragments, i.e., a divalent fragment containing two Fab fragments linked by disulfide bridges in the hinge region; Fd fragments consisting of V H and CH1 domains or; V L and V H Fv fragments consisting of domains; V H domains dAb fragments consisting of (Ward et al., 1989 Nature 341 : 544-546); and isolated CDRs. Exemplary antigen-binding fragments include the CDRs of secukinumab as described in SEQ ID NOs: 1-6 and 11-13 (Table 1), preferably the heavy chain CDR3. Furthermore, the two domains of the Fv fragment, V L and V H are encoded by separate genes, but when these pair with each other, a monovalent molecule (known as a single-chain Fv (scFv); e.g., L the V H region and the V region pair to form a monovalent molecule (known as a single-chain Fv (scFv); e.g., Bird et al., 1988 Science 242:423-426; and Huston et al., 1988 Proc. Natl. Acad. Sci. 85 : 5879-5883 (see) to form), and enables it to act as) to form These can be linked using recombinant methods by a synthetic linker. Such a single-chain antibody is also intended to be encompassed by the term "antibody". Single-chain antibodies and antigen-binding portions are obtained using conventional techniques known to those skilled in the art.

[0019] "Isolated antibody", as used herein, refers to an antibody that substantially does not contain other antibodies having different antigen specificities (e.g., an isolated antibody that specifically binds to IL-17 substantially does not contain antibodies that specifically bind to antigens other than IL-17). As used herein, the term "monoclonal antibody" or "monoclonal antibody composition" refers to the preparation of antibody molecules of a monoclonal composition. The term "human antibody", as used herein, intends to include antibodies having variable regions whose framework and CDR regions are derived from sequences of human origin. A "human antibody" need not be produced by a human, human tissue, or human cell. The human antibodies of the present disclosure can include amino acid residues not encoded by human sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro, at junctions during recombination of antibody genes, by N-nucleotide addition at junctions in vivo, or by somatic hypermutation in vivo). In some embodiments of the disclosed processes and compositions, the IL-17 antibody is a human antibody, an isolated antibody, and / or a monoclonal antibody. For example, by random or site-directed mutagenesis in vitro, at junctions during recombination of antibody genes, by N-nucleotide addition at junctions in vivo, or by somatic hypermutation in vivo). In some embodiments of the disclosed processes and compositions, the IL-17 antibody is a human antibody, an isolated antibody, and / or a monoclonal antibody. antibody.

[0020] The term "IL-17" refers to IL-17A, which was previously known as CTLA8, Wild-type IL-17A, polymorphic variants and functional equivalents of IL-17A from various species (e.g., human, mouse and monkey) are included. The functional equivalents of IL-17A according to the present disclosure preferably have at least about 65%, 75%, 85%, 95%, 96%, 97%, 98%, and even 99% overall sequence identity with wild-type IL-17A (e.g., human IL-17A) and substantially retain the ability to induce IL-6 production by human skin fibroblasts. The term "K D " is intended to refer to the dissociation rate of a particular antibody-antigen interaction. The term "K D ", as used herein, refers to the ratio of K d to K a (i.e., K d / K a ) and is intended to refer to the dissociation constant, expressed as molar concentration (M), obtained therefrom. The K D value for an antibody can be determined using methods established in the art. A preferred method for determining the K D of an antibody is by using surface plasmon resonance or a biosensor system such as the Biacore® (registered trademark) system. In some embodiments, the IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab, binds to human IL-17 with a K D of about 100 - 250 pM. The term "affinity" refers to the strength of the interaction between an antibody and an antigen at a single antigenic site. Within each antigenic site, the variable regions of the antibody "arms" interact with multiple sites through weak non-covalent forces.

[0021] D d a d a D D D

[0022] It then interacts with the antigen, and the greater the interaction, the stronger the affinity. For various species of IL-17 Standard assays for evaluating the binding affinity of antibodies to, for example, include ELISA, western blot and RIA, which are known in the art. The binding kinetics of antibodies (e.g., , binding affinity) can also be evaluated by assays known in the art, for example using Biacore (registered trademark) analysis.

[0023] Determined according to methodologies known in the art and one or more of these IL- 17 functional properties (e.g., biochemical, immunochemical, cellular, physiological or other biological activities whatever) "inhibiting" antibodies are those that, in the absence of the antibody (or in the presence of a control antibody of irrelevant specificity), show a statistically significant decrease in that particular activity compared to what is seen. Antibodies that inhibit IL-17 activity, for example, cause a statistically significant decrease in at least about 10%, at least 50%, 80% or 90% of the measured parameter, and in certain embodiments of the disclosed methods and compositions, the IL-17 antibodies used can inhibit more than 95%, 98% or 99% of the IL-17 functional activity.

[0024] As used herein, "inhibiting IL-6" refers to the ability of an IL-17 antibody or its antigen-binding fragment (e.g., secukinumab) to reduce the production of IL-6 from primary human dermal fibroblasts. The production of IL-6 in primary human dermal fibroblasts is dependent on IL-17 ( Hwang et al.,(2004)Arthritis Res Ther;6: R120-128). Briefly, human dermal fibroblasts are incubated with various concentrations of an antibody having an Fc portion Stimulate with recombinant IL-17 in the presence of a degree of IL-17 binding molecule or human IL-17 receptor Do. The chimeric anti-CD25 antibody Simulect® (basiliximab) can be conveniently used as a negative control. After 16 hours of stimulation, the supernatant is removed and ELI SA is used to quantify for IL-6. An IL-17 antibody or an antigen-binding fragment thereof, for example secukinumab, is tested as described above, i.e., when the inhibitory activity is measured with respect to IL-6 production induced by human IL-17 in human skin fibroblasts it typically has an IC50 for inhibition of IL-6 production (in the presence of 1 nM human IL-17) of about 50 nM or less (e.g., from about 0.01 to about 50 nM). In some embodiments of the disclosed methods and compositions, the IL-17 antibody or an antigen-binding fragment thereof, e.g secukinumab, and functional derivatives thereof have an IC50 for inhibition of IL-6 production as defined above of about 20 nM or less, more preferably about 10 nM or less, more preferably about 5 nM or less, more preferably about 2 nM or less, more preferably about 1 nM or less. .

[0025] The term "derivative", unless otherwise indicated, refers to an amino acid sequence variant and covalent modification (e.g., pegylation, deamidation, hydroxylation, phosphorylation, methylation, etc.) of, for example, a specific sequence (e.g., a variable domain), an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab, as defined by the present disclosure. "Functional derivatives" include molecules having qualitative biological activities common to the disclosed IL -17 antibodies. Functional derivatives include fragments and peptide analogs of the IL-17 antibodies disclosed herein. Fragments are disclosed It includes, for example, regions within the sequence of a polypeptide of a specific array as shown. Disclosed herein Functional derivatives of IL-17 antibodies (e.g., functional derivatives of secukinumab) are described herein the V of the IL-17 antibodies and antigen-binding fragments thereof disclosed herein H and / or V L sequences (e.g., Table 1's V H and / or V L sequences) and have an overall sequence identity of at least about 65%, 75%, 85%, 95%, 96% , 97%, 98%, and even 99% for V H and / or V L domains and preferably retain substantially the ability to bind to human IL-17 or inhibit IL-6 production by human skin fibroblasts induced by, for example, IL-1 7.

[0026] The expression "substantially identical" means that the relevant amino acid or nucleotide sequence (e.g., V H or is V L domain) is identical to a specific reference sequence or has non-substantial differences (e.g., due to conservative substitutions of amino acids ). Non-substantial differences include minor amino acid changes such as one or H or L two substitutions in the 5-amino acid sequence of a specific region (e.g., V domain). In the case of an antibody, the second antibody has the same specific heterogeneity and has an affinity of at least 50%. Sequences substantially identical to the sequences disclosed herein (e.g., at least about 85% sequence identity) are also part of this application . In some embodiments, the sequence identity of the derivative IL-17 antibody (e.g., a derivative of secukinumab, e.g., a secukinumab biosimilar antibody) is about 90 %, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 9 8%, or may be 99% or more.

[0027] As used herein, "identity" with respect to a native polypeptide and its functional derivatives is defined as the percentage of amino acid residues within a candidate sequence that are identical to the residues of the corresponding native polypeptide, after aligning the sequences as needed to obtain the maximum percent identity, introducing gaps, and assuming that no conservative substitutions are considered part of the sequence identity. N- or C-terminal extensions or insertions are not construed to decrease identity. Methods and computer programs for alignment are well known. Percent identity can be determined by standard alignment algorithms, such as the Basic Local Alignment Search Tool (BLAST) described by Altshul et al. ((1990) J. Mol. Biol., 215:403 - 410); the algorithm of Needleman et al. ((1970) J. Mol. Biol., 48:444 - 453); or the algorithm of Meyers et al. ((1988) Comput. Appl. Biosci., 4:11 - 17). A set of parameters can be a Blosum 62 score matrix with a 12 gap penalty, a 4 gap extension penalty, and a 5 frameshift gap penalty. Percent identity between two amino acid or nucleotide sequences can be determined using the ALIGN program (version 2.0) incorporated with the PAM120 weight residue table, a 12 gap length penalty, and a 4 gap penalty, by E. Meyers and W. Miller ((1 percent identity, after aligning the sequences as needed to obtain the maximum percent identity and introducing gaps, is the percentage of amino acid residues within the candidate sequence that are identical to the residues of the corresponding native polypeptide, and no conservative substitution is considered part of the sequence identity. N- or C-terminal extensions or insertions are not construed to decrease identity. Methods and computer programs for alignment are well known. Percent identity can be determined by standard alignment algorithms, such as the Basic Local Alignment Search Tool (BLAST) described by Altshul et al. ((1990) J. Mol. Biol., 215:403 410); the algorithm of Needleman et al. ((1970) J. Mol. Biol., 48:444 453); or the algorithm of Meyers et al. ((1988) Comput. Appl. Biosci., 4:11 17). A set of parameters can be a Blosum 62 score matrix with a 12 gap penalty, a 4 gap extension penalty, and a 5 frameshift gap penalty. Percent It can also be determined using the algorithm of 989)CABIOS,4:11-17) .

[0028] "Amino acid" refers to all L-α-amino acids of natural origin, for example, D-amino acids are included. The expression "amino acid sequence variant" refers to a molecule whose amino acid sequence is somewhat different when compared with the sequence according to the present disclosure. For example, an amino acid sequence variant of an antibody according to the present disclosure of a specific sequence still has the ability to bind to human IL-17, or inhibits the IL-6 production of human skin fibroblasts induced by IL-17, for example . An amino acid sequence variant includes substitution variants (where at least one amino acid residue in the polypeptide according to the present disclosure is removed and another amino acid is inserted at the same position), insertion variants (where one or more amino acids are inserted immediately adjacent to a specific amino acid in the polypeptide according to the present disclosure), and deletion variants (where one or more amino acids in the polypeptide according to the present disclosure are removed).

[0029] The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient.

[0030] The term "administering" with respect to a compound, for example, an IL-17 binding molecule or another agent, is used to refer to the delivery of that compound to a patient by any route.

[0031] As used herein, a "therapeutically effective amount" is a single dose or repeated doses administered to a patient (such as a human) that treats, prevents, or ameliorates at least one symptom of a disorder or a recurrent disorder. ​​​​​​​​Preventing onset, effecting a cure, delaying, reducing the severity, effecting a recovery, or prolonging the survival of a patient beyond that predicted in the absence of such treatment, an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-1 7 antibody or an antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof), which is effective for such use, refers to the amount of the individual active ingredient (e.g., an IL-17 antagonist, such as secukinumab) when administered alone. When applied to an individual active ingredient in combination, the term refers to the combined amount of the active ingredients that provide a therapeutic effect, whether administered consecutively or simultaneously, in the combination.

[0032] The term "treatment" or "treating" as used herein refers to the application or administration to a subject, or to an isolated tissue or cell line derived from a subject, of an IL-17 antibody according to the present disclosure, such as secukinumab or ixekizumab or a pharmaceutical composition comprising said anti-IL-17 antibody, wherein the subject has a predisposition to the onset of a particular disease (e.g., HS), a symptom associated with said disease (e.g., HS), or said disease (e.g., HS, if applicable), and the purpose is to effect a cure (if applicable) of one or more symptoms of the disease, delay the onset, reduce the severity, alleviate, effect a recovery, improve the disease, reduce or improve any associated symptom of the disease or the predisposition to the onset of the disease. The term "treatment" or "treating" includes treating patients suspected of having the disease and patients diagnosed as being ill or suffering from a disease or medical condition, and also suppressing clinical recurrence ​​​is included.

[0033] As used herein, the expression "population of patients" is used to mean a group of patients. In some embodiments of the disclosed methods, an IL-17 antagonist (e.g., an IL-17 antibody such as secukinumab) is used to treat a population of HS patients.

[0034] As used herein, the expressions "not previously treated with systemic therapy for HS" and "not received" refer to HS patients who have not previously been treated with systemic agents for HS, such as methotrexate, cyclosporine, biologic agents (e.g., ustekinumab, adalimumab, or other TNFα inhibitors, etc.). Systemic agents (i.e., agents administered orally, by injection, etc.) differ from topical agents (e.g., topical medications and phototherapy) in that systemic agents have a systemic effect (throughout the body) when delivered to a patient. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has not previously received systemic therapy for HS.

[0035] As used herein, the expression "previously treated with a systemic agent for HS" is used to mean a patient who has previously received HS treatment using a systemic agent. Such patients include patients previously treated with biologic agents such as ustekinumab or TNF-α inhibitors, and patients previously treated with non-biologic agents such as cyclosporine. In some embodiments of the present disclosure, the patient has previously been administered a systemic agent for HS. In some embodiments, the patient has previously been administered a systemic agent for HS (e.g., methotrexate , has been previously administered cyclosporine, and this patient has not been previously administered systemic biologic drugs for HS (i.e., drugs produced by living organisms, such as antibodies, receptor decoys such as those from cows) (e.g., ustekinumab, ixekizumab, brodalumab, TNFα inhibitors (etanercept, adalimumab, Remicade, etc.), secukinumab, etc.). In this case, the patient is also referred to as "not having received a biologic." In some embodiments, the patient has not received a biologic.

[0036] As used herein, the term "TNF failure" refers to a patient who has shown an inadequate response or intolerance to previous treatment with a TNFα antagonist (e.g., etanercept, adalimumab, etc.). A patient who has responded appropriately to previous treatment with a TNFα antagonist (e.g., etanercept, adalimumab, etc.) but has been discontinued due to side effects is called "intolerant." TNF failure is sometimes also referred to as a "TNF-IR" patient. In some embodiments, the patient is TNF failed prior to administration of an IL-17 antagonist. As used herein, "selecting" and "selected" with respect to a patient are used to mean that a particular patient is individually selected from a larger group of patients based on (due to) that particular patient having predefined criteria. Similarly, "selectively treating" refers to providing treatment to a patient having a particular disease, where the patient is individually selected based on that particular patient having predefined criteria. Similarly, "selective" "administering to" means administering a drug to a patient individually selected from a larger group of patients based on that particular patient having predefined criteria. Selecting, selectively treating, and selectively administering means that the patient is not delivered a standard treatment regimen based only on membership of patients within a larger group, but rather an individualized treatment based on the patient's individual medical history (e.g., previous treatment interventions, e.g., previous treatment with biologics), biology (e.g., specific gene markers) and / or symptoms (e.g., not meeting specific diagnostic criteria). Selecting as used herein with respect to a method of treatment does not refer to the fortunate treatment of patients having specific criteria, but rather to the intentional selection to treat a patient based on that patient having specific criteria. Thus, selective treatment / administration differs from standard treatment / administration which delivers a specific drug regardless of the patient's individual medical history, symptoms of the disease and / or biology for all patients having a particular disease.

[0037] ​​​​​​​​​​​​​​​​​​Based on having previously shown an inappropriate response to HS treatment of the body, for the treatment is selected.

[0038] As used herein, conventional systemic therapies include antibiotics, steroids, retinoids, humoral therapy, and TNFα inhibitors (e.g., etanercept, infliximab, adali mumab, etc.).

[0039] IL-17 antagonist The various processes, kits, uses, and methods disclosed utilize an IL-17 antagonist, such as for example, an IL-17 binding molecule (e.g., a soluble IL-17 receptor, an IL-17 antibody or an antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody or an antigen-binding fragment thereof). In some embodiments, the IL-17 antagonist is an IL-17 binding molecule, preferably an IL-17 antibody or an antigen-binding fragment thereof.

[0040] In one embodiment, the IL-17 antibody or an antigen-binding fragment thereof comprises at least one immunoglobulin heavy chain variable domain (V H ) comprising hypervariable regions CDR1, CDR2, and CDR3, wherein said CDR1 has the amino acid sequence SEQ ID NO: 1, said CDR2 has the amino acid sequence SEQ ID NO: 2, and said CDR3 has the amino acid sequence SEQ ID NO: 3. In one embodiment, the IL-17 antibody or an antigen-binding fragment thereof comprises at least one L’ immunoglobulin light chain variable domain (V comprising hypervariable regions CDR1', CDR2', and CDR3', and It has SEQ ID NO: 5, and said CDR3’ has the amino acid sequence SEQ ID NO: 6. In one embodiment an IL-17 antibody or an antigen-binding fragment thereof comprises at least one immunoglobulin heavy chain variable domain (V ) containing CDR1-x, CDR2- H x and CDR3-x, said CDR1-x having the amino acid sequence SEQ ID NO: 11, said CDR2-x having the amino acid sequence SEQ ID NO: 12, and said CDR3-x having the amino acid sequence SEQ ID NO: 13 .

[0041] In one embodiment, an IL-17 antibody or an antigen-binding fragment thereof comprises at least one immunoglobulin V H domain and at least one immunoglobulin V L domain, wherein a) the immunoglobulin V H domain comprises (for example, in order) i) the hypervariable regions CDR1, C DR2 and CDR3 (said CDR1 having the amino acid sequence SEQ ID NO: 1, said CDR2 having the amino acid sequence SEQ ID NO: 2, and said CDR3 having the amino acid sequence SEQ ID NO: 3) , or ii) the hypervariable regions CDR1-x, CDR2-x and CDR3-x (said CDR 1-x having the amino acid sequence SEQ ID NO: 11, said CDR2-x having the amino acid sequence SEQ ID NO : 12, and said CDR3-x having the amino acid sequence SEQ ID NO: 13), and b) the immunoglobulin V L domain comprises (for example, in order) the hypervariable regions CDR1’, CD R2’ and CDR3’ (said CDR1’ having the amino acid sequence SEQ ID NO: 4, said CDR 2’ having the amino acid sequence SEQ ID NO: 5, and said CDR3’ having the amino acid sequence SEQ ID NO: 6 ).

[0042] ​In one embodiment, the IL-17 antibody or antigen-binding fragment thereof comprises a) an immunoglobulin heavy chain variable domain (V ) comprising the amino acid sequence shown as SEQ ID NO: 8, b) an immunoglobulin light chain variable domain (V H ) comprising the amino acid sequence shown as SEQ ID NO: 10, c) an immunoglobulin V domain comprising the amino acid sequence shown as SEQ ID NO: 8 and an immunoglobulin V L domain comprising the amino acid sequence shown as SEQ ID NO: 10, d) an immunoglobulin V domain comprising the hypervariable regions shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, H e) an immunoglobulin V domain comprising the hypervariable regions shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, f) an immunoglobulin V L domain comprising the hypervariable regions shown as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13, g) an immunoglobulin V domain comprising the hypervariable regions shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 and an immunoglobulin V H domain comprising the hypervariable regions shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, h) an immunoglobulin V domain comprising the hypervariable regions shown as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13 and an immunoglobulin V L domain comprising the hypervariable regions shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, or i) an immunoglobulin V domain comprising the hypervariable regions shown as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13 and an immunoglobulin V H domain comprising the hypervariable regions shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6. For ease of reference, the Kabat definition-based, also determined by X-ray analysis, also using the method of Chothia and co-workers, secukinumab monoclonal H ... ... ... L ... ... H ... ... L ...

[0043] To facilitate reference, based on the Kabat definition, also determined by X-ray analysis, also using the method of Chothia and co-workers, secukinumab monoclonal ... The amino acid sequences of the hypervariable regions of the [antibody name] are provided in Table 1 below.

[0044] [Table 1]

[0045] In preferred embodiments, the constant region domain also comprises a suitable human constant region domain as, for example, described in “Sequences of Proteins of Immunological Interest”, Kab at E.A.et al, US Department of Health and Human Services, Public Health Service, Na tional Institute of Health. The DNA encoding the VL of secukinumab is described in SEQ ID NO:9 The DNA encoding the V of secukinumab is described in SEQ ID NO:7. H

[0046] In some embodiments, the IL-17 antibody or antigen-binding fragment thereof (e.g., secukinumab ) comprises the three CDRs of SEQ ID NO:10. In other embodiments, the IL-17 antibody or its antigen-binding fragment comprises the three CDRs of SEQ ID NO:8. In other embodiments, the IL-17 antibody or antigen-binding fragment thereof comprises the three CDRs of SEQ ID NO:10 and the three CDRs of SEQ ID NO:8 . The CDRs of SEQ ID NO:8 and SEQ ID NO:10 can be referenced in Table 1. The free cysteine (CysL97) within the light chain can be seen in SEQ ID NO:6.

[0047] In some embodiments, the IL-17 antibody or antigen-binding fragment thereof comprises the light chain of SEQ ID NO:14 It includes a lock. In other embodiments, the IL-17 antibody or its antigen-binding fragment is of SEQ ID NO: 15 heavy chain. In other embodiments, the IL-17 antibody or its antigen-binding fragment is SEQ ID NO: 14 light chain and the heavy domain of SEQ ID NO: 15. In some embodiments, the IL-17 antibody or its antigen-binding fragment includes the three CDRs of SEQ ID NO: 14. In other embodiments, the IL -17 antibody or its antigen-binding fragment includes the three CDRs of SEQ ID NO: 15. In other embodiments the IL-17 antibody or its antigen-binding fragment includes the three CDRs of SEQ ID NO: 14 and SEQ ID NO: 15 of the three CDRs. The CDRs of SEQ ID NO: 14 and SEQ ID NO: 15 can be referred to in Table 1 .

[0048] The hypervariable region can be associated with any type of framework region, but those of human origin are preferred. Suitable framework regions are described in Kabat E.A.et al, ibid. Preferred heavy chain frameworks are human heavy chain frameworks, such as the heavy chain framework of the secukinumab antibody. This consists, in order, of, for example, FR1 (amino acids 1-30 of SEQ ID NO: 8), FR2 (amino acids 36-49 of SEQ ID NO: 8), FR3 ( amino acids 67-98 of SEQ ID NO: 8) and FR4 (amino acids 117-127 of SEQ ID NO: 8) regions. Considering the determined hypervariable regions of secukinumab by X-ray analysis, another preferred heavy chain framework consists, in order, of the FR1-x (amino acids 1-25 of SEQ ID NO: 8 ), FR2-x (amino acids 36-49 of SEQ ID NO: 8), FR3-x (amino acids 61-95 of SEQ ID NO: 8) and FR4 (amino acids 119-127 of SEQ ID NO: 8) regions. Similarly the light chain framework consists, in order, of FR1’ (amino acids 1-23 of SEQ ID NO: 10), FR ​2’ (amino acids 36 - 50 of SEQ ID NO: 10), FR3’ (amino acids 58 - 89 of SEQ ID NO: 10) and FR4’ (amino acids 99 - 109 of SEQ ID NO: 10).

[0049] In one embodiment, the IL-17 antibody or its antigen-binding fragment (e.g., secukinumab) is at least a) in order, a variable domain containing the high-frequency variable regions CDR1, CDR2 and CDR3 and an immunoglobulin heavy chain or its fragment containing the constant region of the human heavy chain or its fragment (wherein CDR1 has the amino acid sequence SEQ ID NO: 1, CDR2 has the amino acid sequence SEQ ID NO: 2 and CDR3 has the amino acid sequence SEQ ID NO: 3), and b) in order, a variable domain containing the high-frequency variable regions CDR1’, CDR2’ and CDR3’ and an immunoglobulin light chain or its fragment containing the constant region of the human light chain or its fragment (wherein CDR1’ has the amino acid sequence SEQ ID NO: 4, CDR2’ has the amino acid sequence SEQ ID NO: 5, and CDR3’ has the amino acid sequence SEQ ID NO: 6), and is selected from human IL-17 antibodies.

[0050] In one embodiment, the IL-17 antibody or its antigen-binding fragment is a) in order, a first domain containing the high-frequency variable regions CDR1, CDR2 and CDR3 (wherein CDR1 has the amino acid sequence SEQ ID NO: 1, CDR2 has the amino acid sequence SEQ ID NO: 2, and CDR3 has the amino acid sequence SEQ ID NO: 3), b) in order, a second domain containing the high-frequency variable regions CDR1’, CDR2 ’ and CDR3’ (wherein CDR1’ has the amino acid sequence SEQ ID NO: 4 and CDR2’ has the amino acid sequence SEQ ID NO: 5 and CDR3’ has the amino acid sequence SEQ ID NO: 6), and c) the N-terminus of the first domain and the C-terminus of the second domain a peptide linker that binds to the C-terminus of the first domain and the N-terminus of the second domain and is selected from a single-chain antibody comprising an antigen-binding site or an antigen-binding fragment thereof.

[0051] Alternatively, the IL-17 antibody or antigen-binding fragment thereof used in the disclosed method may be, according to the sequence a derivative of the IL-17 antibody described herein (e.g., a pegylated variant, a glycosylated variant, an affinity-matured variant, etc.). Alternatively, the V or V H or V L domain of the IL-17 antibody or antigen-binding fragment thereof used in the disclosed method may be a V or V H or V L domain that is substantially identical to the V H or V L domain described herein (e.g., those described in SEQ ID NOs: 8 and 10). The human IL-17 antibody disclosed herein may comprise a heavy chain that is substantially identical to that shown as SEQ ID NO: 15 and / or a light chain that is substantially identical to that shown as SEQ ID NO: 1 4. The human IL-17 antibody disclosed herein may comprise a heavy chain comprising SEQ ID NO: 15 and a light chain comprising SEQ ID NO: 14 . The human IL-17 antibody disclosed herein may comprise a single heavy chain comprising a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 8 and a constant region of a human heavy chain, and a single light chain comprising a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 10 and a constant region of a human light chain. Alternatively, the human IL-17 antibody disclosed herein may comprise a single heavy chain comprising a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 8 and a constant region of a human heavy chain, and a single light chain comprising a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 10 and a constant region of a human light chain. and a single light chain comprising a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 10 and a constant region of a human light chain.

[0052] Alternatively, the IL-17 antibody or antigen-binding fragment thereof used in the disclosed method may, as long as it contains CysL97, have the amino acids of the reference IL-17 antibody shown herein ​​ can be an array variant. The present disclosure includes the V of secukinumab H or V L one or more, typically only a very small number (e.g., 1 to 10 ) of the amino acid residues (other than CysL97) of the domain are changed, for example, by mutation of the corresponding DNA sequence, such as site-directed mutagenesis , also includes an IL-17 antibody or an antigen-binding fragment thereof (e.g., secukinumab). In all such cases of derivatives and variants, the IL-17 antibody or an antigen-binding fragment thereof has an activity of about 50 nM or less, about 20 nM or less, about 10 nM or less, about 5 nM or less, about 2 nM or less, or more preferably about 1 nM or less to inhibit 50% of the activity of 1 nM (= 30 ng / ml) of human IL-1 7, and the inhibitory activity is measured against IL-6 production induced by hu-IL-17 in human skin fibroblasts as described in Example 1 of WO 2006 / 0 13107. As described in Example 1 of WO 2006 / 013107, it is measured against IL-6 production induced by hu-IL-17 in human skin fibroblasts. It is measured against IL-6 production induced by hu-IL-17 in human skin fibroblasts.

[0053] In some embodiments, the IL-17 antibody or an antigen-binding fragment thereof, such as secukinumab binds to an epitope of mature human IL-17 comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, T hr125, Pro126, Ile127, Val128, His129. In some embodiments, the IL-17 antibody, e.g. secukinumab, binds to an epitope of mature human IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80. In some embodiments, the IL- 17 antibody, e.g. secukinumab, binds to an epitope of an IL-17 homodimer having two mature human IL-17 chains (the epitope is Leu74, Tyr85, H on one chain of the IL-17 homodimer having two mature human IL-17 chains (the epitope is Leu74, Tyr85, H on one chain of the IL-17 homodimer having two mature human IL-17 chains (the epitope is Leu74, Tyr85, H on one chain is86, Met87, Asn88, Val124, Thr125, Pro126, Il e127, Val128, His129, and Tyr43, Tyr44, Ar g46, Ala79, Asp80 on the other chain). The numbering scheme of the residues used to define these epitopes is such that residue 1 is the first amino acid of the mature protein (i.e., IL-17A lacks the 23-amino acid N-terminal signal peptide and starts from glycine). The sequence of immature IL-17A is described in Swiss-Prot entry Q16552. In some embodiments, the IL-17 antibody has a K of about 100 - 200 pM (e.g., measured by Biacor (registered trademark) analysis). In some embodiments, the IL-17 antibody has an IC of about 0.4 nM for neutralizing the in vitro biological activity of about 0.67 nM human IL-17A. In some embodiments, the absolute bioavailability of the subcutaneously (SC) administered IL D (e.g., Biacor (registered trademark) analysis). In some embodiments, the IL-17 antibody has an IC of about 0.4 nM for neutralizing the in vitro biological activity of about 0.67 nM human IL-17A. In some embodiments, the absolute bioavailability of the subcutaneously (SC) administered IL -17 antibody is in the range of about 60% - about 80%, e.g., about 7 50 6%. In some embodiments, an IL-17 antibody such as secukinumab has a half-life of disappearance of about 4 weeks ( e.g., about 23 - about 35 days, about 23 - about 30 days, e.g., about 30 days). In some embodiments, the IL-17 antibody (such as secukinumab) has a T of about 7 - 8 days. e.g., about 23 - about 35 days, about 23 - about 30 days, e.g., about 30 days). In some embodiments, the IL-17 antibody (such as secukinumab) has a T of about 7 - 8 days. m ax has.

[0054] Particularly preferred IL-17 antibodies or antigen-binding fragments thereof used in the disclosed methods are human antibodies, particularly those described in Examples 1 and 2 of WO 2006 / 013107 pamphlet It is secukinumab. For use in the disclosed methods, kits, and regimens Other preferred IL-17 antibodies are incorporated herein by reference in their entirety, U.S. Patent No. 8,057,794; U.S. Patent No. 8,003,099; U.S. Patent No. 8,110,191; and U.S. Patent No. 7,838,638, as well as U.S. Patent Application Publication No. 20120034656 and U.S. Patent Application Publication No. 2011 0027290, which are described therein.

[0055] Methods of treatment and use of IL-17 antagonists for HS The disclosed IL-17 antagonists, e.g., IL-17 binding molecules (e.g., IL-1 7 antibodies or antigen-binding fragments thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e.g ., IL-17 receptor antibodies or antigen-binding fragments thereof) can be used in vitro, ex vivo to treat HS patients (e.g., human patients), or incorporated into a pharmaceutical composition for in vivo administration. HS is a chronic, inflammatory, scarring condition that primarily affects the skin intertriginous areas of the body's axillae, groin, inframammary, genitoperineal, and perineal regions. HS is also known as inverse acne. The diagnosis of HS is established by three

[0056] diagnostic criteria: typical lesions (in the initial first lesion, a deep, painful nodule [a blind] boil, or in the second lesion, an abscess, sinus tract, connected scar, and "tombstone" open comedones); typical tissue distribution (axillae groin, genitals, perineum and perianal region, buttocks, and inframammary and intermammary regions; and chronicity and recurrence (Margesson and Danby (2014) Best Pr ., deep, painful nodules [non-opening] boils, or in the second lesion, abscesses, sinus tracts, connected scars, and "tombstone" open comedones); typical tissue distribution (axillae, groin, genitals, perineum and perianal region, buttocks, and inframammary and intermammary regions; and chronicity and recurrence (Margesson and Danby (2014) Best Pr Actices and Res.Clin.Ob.And Gyn 28:1013- 1027). The physical degree of HS can be classified using the Hurley clinical staging (Hurley’s clinical staging) shown in Table 2 below: It can be done:

[0057]

Table 2

[0058] HS is composed of follicular plugs, duct rupture, and secondary inflammation. Patients first experience blockage of the hair follicle ducts, which over time leads to leakage of the ducts and horizontal rupture into the dermis. If the repair of the hair follicle - pilosebaceous (FPSB) fails, the hair follicle fragments stimulate three reactions that initiate the HS disease process. The first is an inflammatory response caused by the innate immune system, which causes suppuration and tissue destruction, leading to a foreign body reaction and extensive scarring. The second reaction results in epithelial - lined cavities that may arise from stem cells of surviving FPSB units from the destruction caused by the inflammatory response. The third, an invasive proliferative gelatinous mass composed of a gel containing inflammatory cells, occurs in most cases and is hypothesized to be the precursor of the epithelial - lined elements described above (see Margesson and Danby (2 014)). As used herein, the expression "slowing the HS disease progression" means slowing any of the aspects of the HS disease process described above, particularly the rate of progression of the inflammatory response. In some embodiments of the present disclosure, treatment with an IL - 17 antagonist (such as secukinumab) slows the HS disease progression.

[0059] The recurrence of HS in patients includes the occurrence of papules, pustules or inflammatory nodules, pain and pruritus, abscesses, drainage, and any combination thereof. As used herein, " HS erythema" (etc.) is defined as at least a 25% increase in the number of abscesses and inflammatory nodules (AN) with a minimum increase in 2AN relative to baseline. In some embodiments of the present disclosure, treatment with an IL-17 antagonist (e.g., secukinumab) according to the disclosed method prevents HS erythema, reduces the severity of HS erythema, and / or reduces the frequency of HS erythema. In some embodiments, when a population of HS patients is treated according to the disclosed method, less than 5%, less than 10%, less than 15%, or less than 20% experience erythema during the first 16 weeks of treatment.

[0060] As used herein, the expression "reducing the severity of HS erythema" etc. means reducing the intensity of HS erythema, e.g., reducing the number and / or size of abscesses and / or inflammatory nodules, reducing the strength of a particular erythema component (e.g., reducing the number, size, thickness, etc. of abscesses and / or inflammatory nodules, reducing the degree of skin irritation (such as pruritus, pain)), and / or reducing the amount of time that erythema (or its components) persists.

[0061] As used herein, the expression "reducing the frequency of HS erythema" etc. means reducing the incidence of HS erythema, e.g., reducing the incidence of abscesses and / or inflammatory nodules. By reducing the frequency of HS erythema, patients experience fewer HS recurrences. will experience. The incidence of erythema can be evaluated by observing the patient over time and determining whether the prevalence of erythema has decreased by determining whether or not it has occurred.

[0062] As used herein, the expression "preventing HS erythema" means precluding future HS erythema and / or erythema components.

[0063] The efficacy of HS treatment can be evaluated using various known methods and means for measuring the HS condition and / or HS clinical response. Some examples include, for example, Hurley y's stage classification, Sartorius score, modified Sartorius score, HS physician overall assessment (HS-PGA) score, visual analog scale (VAS) or numerical rating scale (NRS) for assessing skin-related pain, dermatology life quality index (DLQI )、HS clinical response (HiSCR) based on the total of abscesses and inflammatory nodules, simplified HiSCR, EuroQuol-5D (EQ5D), hospital anxiety and depression scale for anxiety and depression in etiology, healthcare resources utilization, Hidradenitis Suppurativa Severity Index (HSSI), Work productivity index (WPI), inflamed body surface area (BSA), Acne Inversa Severity Index (AISI), etc. (for example, Deckers and healthcare resources utilization), Hidradenitis Suppurativa Severity Index (HSSI), Work productivity index (WPI), inflamed body surface area (BSA), Acne Inversa Severity Index (AISI), etc. (for example, Deckers and ndex) (WPI), inflamed body surface area (BSA), Acne Inversa Severity Index (AISI), etc. (for example, Deckers and ity Index) (AISI), etc. (for example, Deckers and Prens(2016) Drugs 76:215-229; Sartorius et al.(2009) Br.J.Dermatol 161:831-39; Chiricozzi et al.(2015) Wounds 27(10):258-264 (see). tal.(2009) Br.J.Dermatol 161:831-39; Chir icozzi et al.(2015) Wounds 27(10):258-264 (see). In some embodiments, HS patients achieve HiSCR in response to HS treatment. In some embodiments, at least 41%, at least 50%, at least 51%, at least 61 %, or at least 71% of a population of HS patients achieve HiSCR by week 16 of treatment when treated according to the disclosed methods.

[0064] Preferred scoring systems for treatment response are HiSCR, simplified HiSCR, N RS (especially NRS30), modified Sartorius score, HS-PGA, inflammatory variables (number of abscesses, inflammatory nodules, and / or draining fistulas), and DLQI.

[0065] Hidradenitis Suppurativa Clinical Response (HiSCR) is a measure of clinical response to HS treatment. The HiSCR response to treatment (compared to baseline) is as follows: 1 ) at least a 50% decrease in abscesses and inflammatory nodules, and 2) no increase in the number of abscesses, and ) no increase in the number of draining fistulas. As used herein, "simplified HiSCR" or "sH iSCR" refers to a modified HiSCR that does not include the abscess count relative to baseline (above, 2)) when assessing lesion progression. In preferred embodiments, HS patients achieve simplified HiSCR in response to HS treatment. In some embodiments, a population of HS patients responds to HS treatment and achieves simplified HiSCR. When treated according to the disclosed method, at least 41%, at least 50%, at least 51%, at least 61%, or at least 71% achieve a simplified HiSCR by week 16 of treatment. Achieve a simplified HiSCR.

[0066] Pain can be evaluated using a Numerical Rating Scale (NRS). In some embodiments, HS patients achieve an improvement in the NRS in response to HS treatment. NRS30 is defined as at least a 30% reduction in pain from baseline in patients with a baseline score of 3 or more, and at least a 1 unit decrease from baseline in the Patient’s Global Assessment (PGA) of Skin Pain. In some embodiments, HS patients achieve NRS30 in response to HS treatment. In some embodiments, at least 30%, at least 40%, at least 50%, or at least 60% of a population of HS patients achieve NRS30 by week 16 of treatment when treated according to the disclosed method.

[0067] The DLQI is the most established measure of dermatology quality of life. It consists of questions regarding the impact of skin disease on feelings and other aspects of daily life activities during the previous week. Each question is scored from 0 (not at all) to 3 (very much so). A total of 30 points is the maximum score, where 0 - 1 is considered no impact on the patient’s life, 2 - 5 is small, 6 - 10 is moderate, 11 - 20 is very large, and (see n Exp Dermatol 19:210-16). In some embodiments HS patients achieve an improvement in DLQI in response to HS treatment.

[0068] The Sartorius HS score (also called the HS score or HSS) is assigned by counting the areas, nodules, and sinus tracts involved in HS patients (Sa rtorius et al. (2003) Br J Dermatol 149:21 1-13). The modified Sartorius HS score is a modified version of the original HSS that makes some simplifications to make it more practical, such as reducing the number of individual lesions included in the score, changing the number of points assigned to each parameter, etc. (Sartorius et al. (2009) Br.J Dermatol.16 1:831-839). In some embodiments, HS patients achieve an improvement in modified Sartorius HS in response to HS treatment. In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment. In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment. 1:831-839). In some embodiments, HS patients achieve an improvement in modified Sartorius HS in response to HS treatment. In some embodiments, HS patients achieve an improvement in modified Sartorius HS in response to HS treatment. In some embodiments, HS patients achieve an improvement in modified Sartorius HS in response to HS treatment.

[0069] The HS Physician's Global Assessment (HS-PGA) is a six-point assessment scale (score range 0 ~5) based on the number of HS lesions (i.e., abscesses, draining fistulas, inflammatory nodules, and non-inflammatory nodules) (Chiricozzi et al. (2015) Wounds 27( 10):258-264). In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment. In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment. In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment. In some embodiments, HS patients achieve an improvement in HS-PGA in response to HS treatment. In some embodiments, HS patients achieve a clear, minimal, or mild HS-PGA score with at least a two-grade improvement from baseline in response to HS treatment.

[0070] In some embodiments, the patient is treated for HS for at least 36 weeks, at least 48 weeks, at least 52 weeks, or at least 2 years, according to the claimed method. In some embodiments, when a population of HS patients is treated according to the disclosed method, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the patients who responded to treatment by week 16 (e.g., achieved HiSCR or simplified HiSCR by week 16) had a sustained response 1 year ( 52 weeks) after treatment. As used herein, the term "sustained" means that the remission or goal (e.g., pain reduction, inflammation reduction) is substantially maintained for a given period of time.

[0071] As used herein, the expression "moderate to severe" refers to an HS disease having ≧5 active inflammatory lesions (i.e., abscesses and / or inflammatory nodules) that affect at least two different anatomical regions. In some embodiments, the HS patient has moderate to severe HS disease.

[0072] In some embodiments, the patient has been diagnosed with HS for at least 1 year.

[0073] In some embodiments, the patient does not have extensive scarring as a result of HS (i.e., <20 draining or non-draining fistulas).

[0074] In some embodiments, the patient has previously demonstrated an inadequate response to conventional systemic HS therapies as previously shown

[0075] ​​​​​​In some embodiments, the patient is an adolescent patient (≥ 1 2 years old) having moderate to severe HS. In some embodiments, the patient is an adult patient having moderate to severe HS.

[0076] In some embodiments, in response to treatment according to the claimed method, the patient experiences a rapid reduction in pain measured by VAS or NRS, as early as one week after the first dose.

[0077] In some embodiments, systemic therapy is indicated for the patient, i.e., the HS disease is severe enough to require systemic intervention (e.g., > 5% BSA, Hurley stage II or II, etc.).

[0078] In some embodiments, the patient is an adult human patient having HS. In some embodiments, the patient is a pediatric human patient having HS. The upper age limit used to define pediatric patients varies among experts and may include adolescents up to the age of 21 years (see, for example, Berhman RE, Kliegman R, Arvin AM, Nelson WE. Nelson Textbook of Pediatrics, 15th Ed. Philadelphia: W.B. Saunders Company; 19 96; 2. Rudolph AM, et al. Rudolph’s Pediatrics, 21st Ed. New York: McGraw-Hill; 2002; and A very MD, First LR. Pediatric Medicine, 2nd Ed. Baltimore: Williams & Wilkins; 1994). See also ID=41 ​​)。As used herein, the term "pediatric" generally refers to a human who is ≧ 16 years old (this is the definition of a human pediatric used by the US FD A). However, other examples of pediatric patients include humans who are ≧ 14 years old and ≧ 12 years old.

[0079] In some embodiments, the pediatric patient is administered an IL-17 antibody (e.g., secukinumab) at a dose of about 300 mg (weekly) by SC injection every week for the first 0, 1, 2, 3, and 4 weeks, and then every 2 weeks thereafter , regardless of the patient's weight.

[0080] In some embodiments, the pediatric patient is administered an IL-17 antibody (e.g., secukinumab) at a dose of about 300 mg (weekly) by SC injection every week for the first 0, 1, 2, 3, and 4 weeks, and then every 4 weeks thereafter (monthly) , regardless of the patient's weight.

[0081] In some embodiments, the pediatric patient is administered an IL-17 antibody (e.g., secukinumab) at a dose of about 75 mg if the patient's weight is < 25 kg or 150 mg if the patient's weight is > 25 kg by SC injection every week for the first 0, 1, 2, 3, and 4 weeks, and then every 2 weeks or every 4 weeks thereafter. In some embodiments, the pediatric patient is administered an IL-17 antibody (e.g., secukinumab) at a dose of about 75 mg if the patient's weight is < 50 kg or 150 mg if the patient's weight is > 50 kg by SC injection every week for the first 0, 1, 2, 3, and 4 weeks, and then every 2 weeks or every 4 weeks thereafter.

[0082] In some embodiments, the pediatric patient is administered an IL-17 antibody (e.g., secukinumab) at a dose of about 150 mg if the patient's weight is < 25 kg or the patient If the weight of is > 25 kg, then SC administration of an IL-17 antibody (such as secukinumab) at a dose of 300 mg (weekly) is administered. In some embodiments, pediatric patients are during weeks 0, 1, 2, 3, and 4, and then every 2 weeks or every 4 weeks thereafter, if the patient's weight is < 50 kg, then approximately 150 mg, or if the patient's weight is > 50 kg, then 300 mg of SC administration of an IL-17 antibody (such as secukinumab) at a dose (weekly) is administered.

[0083] In some embodiments, in response to treatment according to the claimed method, the patient experiences, as early as 1 week after the first dose, a rapid decrease in CRP measured by a standard CRP measurement or a high-sensitivity CRP (hsCRP) measurement. As used herein, "C-reactive protein" and "CRP" refer to serum C-reactive protein, that is, a plasma protein commonly used as an indicator of the acute-phase response to inflammation. The level of CRP in plasma can be expressed in any concentration (e.g., mg / dl, nmol / L). The level of CRP can be measured by various standard measurement methods, such as radioimmuno-diffusion, electroimmunoassay, immunoturbidimetry, E LISA, turbidimetry, fluorescence polarization immunoassay, and laser nephelometry analysis. Testing for CRP can be performed using a standard CRP test or a high-sensitivity CRP (h s-CRP) test (i.e., a high-sensitivity test capable of measuring low levels of CRP in a sample using laser nephelometry analysis). Kits for detecting the level of CRP are available from various companies, such as Calbiotech, Inc, Cayman n Chemical, Roche Diagnostics Corporation and can be measured by . s-CRP) test (i.e., a high-sensitivity test capable of measuring low levels of CRP in a sample using laser nephelometry analysis). Detecting the level of CRP can be performed using kits available from various companies, such as Calbiotech, Inc, Cayman n Chemical, Roche Diagnostics Corporation , Abazyme, DADE Behring, Abnova Corporation , Aniara Corporation, Bio-Quant Inc., Sieme It can be purchased from, for example, ns Healthcare Diagnostics.

[0084] An IL-17 antagonist, for example, an IL-17 binding molecule (e.g., an IL-17 antibody or its antigen-binding fragment, e.g., secukinumab) or an IL-17 receptor binding molecule (e.g., an IL -17 antibody or its antigen-binding fragment), when combined with a pharmaceutically acceptable carrier, can be used as a pharmaceutical composition. Such compositions can contain, in addition to the IL-17 antagonist, a carrier, various diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well-known in the art. The properties of the carrier depend on the route of administration. The pharmaceutical composition for use in the disclosed method can also contain additional therapeutic agents for the treatment of the specific disorder targeted. For example, the pharmaceutical composition can also contain an anti-inflammatory agent. Including such additional factors and / or agents in the pharmaceutical composition can result in a synergistic effect with the IL-17 binding molecule, or minimize the side effects caused by the IL-17 antagonist, for example, an IL-17 binding molecule (e.g., an IL-17 antibody or its antigen-binding fragment, e.g., secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 antibody or its antigen-binding fragment). In a preferred embodiment, the pharmaceutical composition for use in the disclosed method contains 150 mg / ml of secukinumab. The pharmaceutical composition for use in the disclosed method can be manufactured in a conventional manner. In one

[0085] ​​In an embodiment, the pharmaceutical composition is provided in a lyophilized form. For immediate administration, this is dissolved in a suitable aqueous carrier, such as sterile water for injection or sterile buffered saline for injection . If it is desirable to constitute a larger volume of solution for administration by infusion rather than bolus injection, it may be advantageous to incorporate human serum albumin or the patient's own heparinized blood into the saline solution during formulation. The presence of an excess amount of such physiologically inert proteins prevents the loss of antibodies due to adsorption to the walls of the containers and tubes used with the infusion solution. When albumin is used, a suitable concentration is 0.5-4.5% by weight of the saline solution. Other formulations include liquid formulations that are ready for use.

[0086] Antibodies, such as antibodies against IL-17, are typically formulated in an aqueous form that is immediately parenterally administrable or as a lyophilized product for reconstitution with a suitable diluent before administration. In a preferred embodiment of the disclosed methods and uses, an IL-17 antagonist, such as an IL-17 antibody, such as secukinumab, is formulated as a ready-to-use (i.e., stable and immediately usable) liquid pharmaceutical formulation. In some embodiments of the disclosed methods and uses, an IL-17 antagonist, such as an IL-17 antibody, such as secukinumab, is formulated as a lyophilized product. A suitable lyophilized formulation can be reconstituted in a small volume of liquid (e.g., 2 ml or less, such as 2 ml, 1 ml, etc.) to enable subcutaneous administration and can provide a solution with low levels of antibody aggregation. The use of an antibody as an active ingredient of a medicament is exemplified by HERCEPTIN™ (trastuzumab), RITUXAN™ (rituximab), including products such as Tuximab), SYNAGIS (trademark) (palivizumab), etc., currently , are widely popular. Techniques for the purification of antibodies to pharmaceutical grade are well-known in the art . When a therapeutically effective amount of an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof) is administered by intravenous, cutaneous, or subcutaneous injection, the IL-17 antagonist will be in the form of a pyrogen-free parenterally acceptable solution. A pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection may contain, in addition to the IL-17 antagonist, sodium chloride, Ringer's solution, dextrose, dextrose and sodium chloride, lactated Ringer's solution, or other isotonic vehicles such as those well-known in the art .

[0087] When practicing some of the methods of treatment or use of the present disclosure, a therapeutically effective amount of an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof) is administered to a patient, such as a mammal (e.g., a human). The disclosed methods are understood to provide for the treatment of HS patients using an IL-17 antagonist (e.g., secukinumab), although this does not exclude the possibility that, if a patient is ultimately treated with an IL-17 antagonist, such IL-17 antagonist therapy will necessarily be monotherapy. Indeed, if a patient is selected for treatment with an IL-17 antagonist, the IL-17 antagonist (e.g., secukinumab) may, according to the methods of the present disclosure, be administered alone or in combination with other therapeutics for HS In combination with other agents and therapies for treating a patient, for example, at least one additional HS agent can be administered in combination. When co-administered with one or more additional HS agents, the IL-17 antagonist can be administered simultaneously with or sequentially to the other agent. When administered sequentially, the attending physician determines the appropriate order of administration of the IL-17 antagonist in combination with the other agent and the appropriate dosage for co-delivery.

[0088] A variety of therapies can be beneficially combined with the disclosed IL-17 antibodies, such as secukinumab, during HS treatment. Such conventional therapies include topical treatments (creams [non-steroidal or steroidal], washes, disinfectants), systemic treatments (e.g., using biologics, antibiotics, hormones, retinoids, or chemical entities), disinfectants, photodynamic therapy, and surgical interventions (laser, drainage or incision, excision). Additional combination therapies include the use of JAK inhibitors, IL-23 targeted therapies (e.g., guselkumab), microbiome therapy, and sclerotherapy.

[0089] Non-limiting examples of topical HS agents for use in combination with the disclosed IL-17 antibodies, such as secukinumab, include benzoyl peroxide, topical steroid creams, aminoglycoside topical antibiotics, such as clindamycin, gentamicin, and erythromycin, resorcinol cream, iodine scrub, and chlorhexidine.

[0090] For use in systemic treatment in combination with the disclosed IL-17 antibodies, such as Non-limiting examples of HS agents further include IL-17 antagonists (ixekizumab b, brodalumab, CJM112), tumor necrosis factor α (TNF-α) blockers (Enbre l® (etanercept), Humira® (adalimumab), Re micade® (infliximab), and Simponi® (gol imumab), etc.), interleukin 12 / 23 blockers (Stelara® ( ustekinumab), tasonicitinib, and briakinumab, etc.), p19 inhibitors, PDE4 inhibitors, leukotriene A4 hydrolase inhibitors, complement pathway inhibitors, C5a inhibitors, IL -1 antagonists (canakinumab, rilonacept, anakinra), CXCR1 / 2 inhibitors , IL-18 antagonists, IL-6 antagonists, CD20 antagonists, C TLA4 antagonists, IL-8 antagonists, B cell depletors (depletor) (especially CD20 antagonists, as well as BAFF-R and CD40 antagonists), I L-21 antagonists, IL-22 antagonists, VEGF antagonists, CXC L antagonists, MMP antagonists, and defensin antagonists (e.g., receptor decoys, antagonist antibodies, etc.) may be mentioned.

[0091] Additional HS agents for use in combination with the disclosed IL-17 antibodies such as secukinumab during the treatment of HS include retinoids, such as acitretin (e.g., Soriat ane®) and isotretinoin, etc., immunosuppressants (e.g., rapamycin , T cell blockers [e.g., Amevive® (alefacept) and Rapt iva (Registered Trademark) [Efazumab], Cyclosporine, Methotrexate, Mycophenolic Mofetil Mycophenolate, Mycophenolic Acid, Leflunomide, Tacrolimus, etc.), Hydro xyurea (e.g., Hydrea (Registered Trademark)), Sulfasalazine, 6-Thioguanine , Fumarate (e.g., Dimethyl Fumarate and Fumaric Acid Esters), Azathioprine, Co lchicine, Acitretin, Steroids, Corticosteroids, Certolizumab, Ap remilast, Mometasone, Rosiglitazone, Pioglitazone, Botulinum Toxin, Triam cinolone, IFX-1 (InflaRx), Bimekizumab (UCB), MaBp1 (XB iotech), LY-3041658 (Eli Lilly), TE-2232 (Im munwork), NSAID, Prescription Narcotics, Ketoprofen, Codeine, Gabapenti n, Pregabalin Gentanyl, Antibiotics ( Topical, Oral, IV) (e.g., Clindamycin, Rifampin, Tetracycline, Sarecycline, Doxycycline, Minocycline, Lymecycline, Trimethoprim -Sulfamethoxazole, Erythromycin, Ceftriaxone, Moxifloxacin , Metronidazole, Alone or in Combination), Corticosteroids (Injectable or Oral), Anti-Androgen / Hormone Therapy (Oral Contraceptives, Spironolactone, Finaster ide, Dutasteride, Progesterone IUD, Cyproterone Acetate, Ethinyl Estradi ol, Gestoden, Norgestimate, Desogestrel, Drospirenone, Spironola ctone), Triamcinolone Acetonide, MEDI8968, Hydroxychloroquine, Da psone, Metformin, Adapalene, Azelaic Acid, and Zinc are included.

[0092] The disclosed kits, methods, and preferred combinations for use include TNFα inhibitors (such as adalimumab) or IL-1β blockers (such as canakinumab) in combination with an IL-17 binding molecule (such as an IL-17 antibody or an antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor binding molecule (such as an IL-17 receptor antibody or an antigen-binding fragment).

[0093] One of ordinary skill in the art will be able to recognize the appropriate dosages of the above-described HS agents for co-delivery with the disclosed IL-17 antibodies, such as secukinumab.

[0094] IL-17 antagonists, such as IL-17 binding molecules (such as IL-17 antibodies or antigen-binding fragments thereof, such as secukinumab) or IL-17 receptor binding molecules (such as, IL -17 receptor antibodies or antigen-binding fragments thereof) are preferably administered parenterally, such as intravenously (such as into the antecubital or other peripheral veins), intramuscularly, or subcutaneously. The duration of intravenous (IV) therapy using the pharmaceutical compositions of the present disclosure varies depending on the severity of the disease and condition being treated and the individual response of each individual patient. Subcutaneous (SC) therapy using the pharmaceutical compositions of the present disclosure is also contemplated. A healthcare provider determines the appropriate duration of IV or SC therapy using the pharmaceutical compositions of the present disclosure and the timing of administration of this therapy. In a preferred embodiment , the IL-17 antagonist (such as secukinumab) is administered via the subcutaneous (SC) route.

[0095] IL-17 antagonists, such as, IL-17 binding molecules (such as, IL-17 antibodies or ​​​​Its antigen-binding fragment, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., an IL-17 receptor antibody or its antigen-binding fragment) can be administered intravenously (IV) to a patient, for example, twice weekly at about 10 mg / kg during weeks 0, 2, and 4, and then, for example, starting in week 6, and subcutaneously (SC) to the patient at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg ) every two weeks. In this regimen, the patient can receive about 10 mg / kg IV during weeks 0, 2, and 4, and then about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg ) of an IL-17 antagonist (such as secukinumab) SC during weeks 6, 8, 10, 12, 1 4, and other intervening weeks. Alternatively, an IL-17 antagonist, such as an IL-17-binding molecule (e.g., an IL-1 7 antibody or its antigen-binding fragment, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., an IL-17 receptor antibody or its antigen-binding fragment) can be administered intravenously (IV) to a patient, for example, twice weekly at about 10 mg / kg during weeks 0, 2, and 4, and then, for example, starting

[0096] in week 8, and subcutaneously (SC) to the patient at about 300 mg to about 450 mg (e.g., about 300 m g, about 450 mg) monthly (every 4 weeks). In this regimen, the patient can receive about 10 mg / kg IV during weeks 0, 2, and 4, and then about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) of an IL-17 antagonist (such as secukinumab) SC during weeks 8, 1 2, 16, 20, and other intervening weeks. Alternatively, an IL-17 antagonist, such as an IL-17-binding molecule (e.g., an IL-1 7-binding molecule (e.g., an IL-17 antibody or its antigen-binding fragment, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., an IL-17 receptor antibody or its antigen-binding fragment) can be administered intravenously (IV) to a patient, for example, twice weekly at about 10 mg / kg during weeks 0, 2, and 4, and then, for example, starting in week 8, and subcutaneously (SC) to the patient at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) every four weeks. In this regimen, the patient can receive about 10 mg / kg IV during weeks 0, 2, and 4, and then about 300 mg to about 450 mg (e.g., about 300 mg,

[0097] about 450 mg) of an IL-17 antagonist (such as secukinumab) SC during weeks 8, 1 2, 16, 20, and other intervening weeks. 7 antibodies or antigen-binding fragments thereof, such as secukinumab) or IL-17 receptor-binding molecules (e.g., for example, an IL-17 receptor antibody or antigen-binding fragment thereof) can be administered subcutaneously to a patient, for example, at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) per week during weeks 0, 1, 2, and 3, and then, for example, starting during week 4, at about 300 mg to about 4 50 mg (e.g., about 300 mg, about 450 mg) every two weeks and administered subcutaneously to the patient. In this regimen, the patient is administered subcutaneously about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) of an IL-17 antagonist (e.g., secukinumab) at weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, and other intervals.

[0098] Preferably, the IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-17 antibody or antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., an IL-17 receptor antibody or antigen-binding fragment thereof) can be administered subcutaneously to a patient, for example, at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) per week during weeks 0, 1, 2, and 3, and then, for example, starting during week 4, at about 30 0 mg to about 450 mg (e.g., about 300 mg, about 450 mg) every month (every 4 weeks) and administered subcutaneously to the patient. In this regimen, the patient is administered subcutaneously about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) of an IL-17 antagonist (e.g., secukinumab) at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and other intervals.

[0099] Alternatively, the IL-17 antagonist, such as an IL-17 binding molecule (e.g., IL-1 7 antibodies or antigen-binding fragments thereof, such as secukinumab) or IL-17 receptor-binding molecules (e.g., e.g., an IL-17 receptor antibody or antigen-binding fragment thereof) can be administered subcutaneously to a patient in a dose sufficient to provide a trough concentration of greater than 30 mcg / mL, greater than 40 mcg / mL, greater than 60 mcg / mL, greater than 80 mcg / mL, or greater than 100 mcg / mL in the maintenance regimen. .

[0100] More preferably, an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-17 antibody or antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., an IL-17 receptor antibody or antigen-binding fragment thereof) can be administered to a patient without a loading regimen. For example, this antagonist can be administered subcutaneously to a patient at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) every two weeks. In this manner, a patient can be administered subcutaneously about 3 00 mg to about 450 mg (e.g., about 300 mg, about 450 mg) of an IL-17 antagonist (e.g., secukinumab) at weeks 0, 2, 4, 6, 8, 12, and others.

[0101] Alternatively, an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-1 7 antibody or antigen-binding fragment thereof, such as secukinumab) or an IL-17 receptor-binding molecule (e.g., e.g., an IL-17 receptor antibody or antigen-binding fragment thereof) can be administered to a patient without a loading regimen. For example, this antagonist can be administered subcutaneously to a patient at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg) every four weeks. In this manner, a patient can be administered subcutaneously about 300 mg at weeks 0, 4, 8, 12, 16, 20, and others. ​​mg to about 450 mg (e.g., about 300 mg, about 450 mg) of an IL-17 antagonist (e.g., secukinumab) is administered SC.

[0102] Alternatively, an IL-17 antagonist, e.g., an IL-17 antibody, e.g., secukinumab, may be delivered locally using intralesional injection and also (e.g., using the technologies described in, e.g., U.S. Patent Nos. 8,734,429; 9,492,378; 9,45 6,988; 9,415,004; 9,6297,99; 9,757,54 8; 9,757,514; 9,402,806; U.S. Patent Application Publication Nos. 2 017 / 0189659; 2017 / 0100459) orally to the intestinal lumen.

[0103] For certain patients, e.g., by week 12, 16, 20, 24, 48, or 52 of treatment, for patients with HS who exhibit an inadequate response to treatment with an IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-17 antibody or antigen-binding fragment thereof, e.g., secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody or antigen-binding fragment thereof) (e.g., as measured by any of the HS scoring systems disclosed herein, e.g., HiSCR, Simple HiSCR, NRS [especially NRS30], Modified Sartorius Score, HS-PGA, inflammatory variables (number of abscesses, inflammatory nodules, and / or draining fistulas), DLQI, etc.), dose escalation may be required. Thus, the SC dosage of secukinumab is about 300 mg to about 450 mg (SC), for example, about 350 mg, about 400 mg, about 450 mg (original dose of 300 mg); may be greater than about 500 mg, about 550 mg, about 600 mg (original dose of 450 m g); similarly, the IV dosage may be greater than about 10 mg / k g, for example, about 11 mg / kg, 12 mg / kg, 15 mg / kg, 20 mg / kg, 2 5 mg / kg, 30 mg / kg, 35 mg / kg, etc. For certain patients, for example, HS patients presenting adverse events or adverse reactions to treatment with an IL-17 antagonist (e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab), it will also be understood that dose reduction may be required. Thus, the dosage of an IL -17 antagonist (e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) may be about 300 mg to about 450 mg (SC), for example, about 250 mg, about 2 00 mg, about 150 mg (original dose of 300 mg); may be less than about 400 mg, about 350 mg, about 300 mg (original dose of 450 mg), etc. Similarly, the I V dosage may be less than about 10 mg / kg, for example, about 9 mg / kg, 8 mg / kg, 5 mg / kg 4 mg / kg, 3 mg / kg, 2 mg / kg, 1 mg / kg, etc. In some embodiments, an IL-17 antagonist, e.g., an IL-17-binding moiety (e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) or an IL-1 7 receptor-binding molecule (e.g., an IL-17 receptor antibody or an antigen-binding fragment thereof) can be administered to a patient at an initial dose of 300 m g or 450 mg (SC delivery), and this dose can be adjusted as needed, as determined by the physician, to about 450 mg (original dose of 300 mg after that, as determined by the physician, as needed, to about 450 mg (original dose of 300 mg dose), etc. In some embodiments, an IL-17 antagonist, e.g., an IL-17-binding moiety (e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) or an IL-1 7 receptor-binding molecule (e.g., an IL-17 receptor antibody or an antigen-binding fragment thereof) can be administered to a patient at an initial dose of 300 mg or 450 mg (SC delivery), and this dose can be adjusted as needed, as determined by the physician, to about 450 mg (original dose of 300 mg it can be gradually increased to about 600 mg (in the case of an original dose of 450 mg).

[0104] As used herein, "fixed dose" refers to a constant dose, i.e., a dose that does not change regardless of the characteristics of the patient. Therefore, a fixed dose is different from a variable dose such as a dose based on body surface area or a dose based on body weight (typically given as mg / kg). In preferred embodiments of the disclosed methods, uses, pharmaceutical compositions, kits, etc., HS patients are administered a fixed dose of an IL-17 antibody, e.g., a fixed dose of secukinumab, e.g., a fixed dose of about 75 mg to about 450 mg of secukinumab, e.g., about 75 mg, about 150 mg, about 300 mg, about 400 mg, or about 450 mg of secukinumab. regardless of the characteristics of the patient. Therefore, a fixed dose is different from a variable dose such as a dose based on body surface area or a dose based on body weight (typically given as mg / kg). weight (typically given as mg / kg). In preferred embodiments of the disclosed methods, uses, pharmaceutical compositions, kits, etc., HS patients are administered a fixed dose of an IL-17 antibody, e.g., a fixed dose of secukinumab, e.g., a fixed dose of about 75 mg to about 450 mg of secukinumab, e.g., about 75 mg, about 150 mg, about 300 mg, about 400 mg, or about 450 mg of secukinumab. a fixed dose of an IL-17 antibody, e.g., a fixed dose of secukinumab, e.g., a fixed dose of about 75 mg to about 450 mg of secukinumab, e.g., about 75 mg, about 150 mg, about 300 mg, about 400 mg, or about 450 mg of secukinumab. mg of secukinumab, e.g., about 75 mg, about 150 mg, about 300 mg, about 400 mg, or about 450 mg of secukinumab. mg, about 400 mg, or about 450 mg of secukinumab are administered.

[0105] The timing of dosing is generally measured from the day of the first administration of secukinumab (also known as the "baseline"). However, healthcare providers often use different naming conventions to clarify the dosing schedule as shown in Table 3. also known as the "baseline"). However, healthcare providers often use different naming conventions to clarify the dosing schedule as shown in Table 3. dosing schedule as shown in Table 3.

[0106]

Table 3

[0107] In particular, week 0 may be considered week 1 by some healthcare providers, while day 0 may be considered day 1 by some healthcare providers. Therefore, different physicians may refer to the same dosing schedule, e.g., a dose is given at 3 weeks / 21st day, 3 weeks / 22nd day, 4 weeks / 21st day, 4 weeks / 22nd day, etc. To maintain consistency, the first week of dosing is referred to herein as the week 0 may be considered week 1 by some healthcare providers, while day 0 may be considered day 1 by some healthcare providers. Therefore, different physicians may refer to the same dosing schedule, e.g., a dose is given at 3 weeks / 21st day, 3 weeks / 22nd day, 4 weeks / 21st day, 4 weeks / 22nd day, etc. To maintain consistency, the first week of dosing is referred to herein as the week 0 may be considered week 1 by some healthcare providers, while day 0 may be considered day 1 by some healthcare providers. Therefore, different physicians may refer to the same dosing schedule, e.g., a dose is given at 3 weeks / 21st day, 3 weeks / 22nd day, 4 weeks / 21st day, 4 weeks / 22nd day, etc. To maintain consistency, the first week of dosing is referred to herein as the 3 weeks / 21st day, 3 weeks / 22nd day, 4 weeks / 21st day, 4 weeks / 22nd day, etc. To maintain consistency, the first week of dosing is referred to herein as the 3 weeks / 21st day, 3 weeks / 22nd day, 4 weeks / 21st day, 4 weeks / 22nd day, etc. To maintain consistency, the first week of dosing is referred to herein as the While it is considered to be week 0, the first day of dosing is considered to be day 1. However, this naming convention is used only to maintain consistency and should not be construed as restrictive, i.e., regardless of whether a physician calls a particular week "week 1" or "week 2", those skilled in the art will understand that the weekly dosing is the definition of the weekly dose of the IL-17 antibody.

[0108] In one dosing regimen, the antibody is administered at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and other intervals. Some providers may refer to this regimen as weekly for 5 weeks and then monthly (or every 4 weeks) starting during week 8, while other providers may refer to this regimen as weekly for 4 weeks and then monthly (or every 4 weeks) starting during week 4. Those skilled in the art will understand that administering injections to a patient at weeks 0, 1, 2, and 3 followed by monthly dosing starting at week 4 is equivalent to: 1) administering injections to a patient at weeks 0, 1, 2, 3, and 4 followed by monthly dosing starting at week 8; 2) administering injections to a patient at weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks; and 3) administering injections to a patient at weeks 0, 1, 2, 3, and 4 followed by monthly dosing.

[0109] In one dosing regimen, the antibody is administered at weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, and other intervals. Some providers may refer to this regimen as weekly for 5 weeks and then every other week (or every 2 weeks) starting during week 6, while other providers may refer to this regimen as weekly for 4 weeks and then every other week (or every 2 weeks) starting during week 4. ​ There may also be providers. Administering to the patient an injection in the 0th, 1st, 2nd, and 3rd weeks, followed by once-weekly (or every two weeks) administration starting in the 4th week is understood by those skilled in the art to be the same as the following: 1) administering to the patient an injection in the 0th, 1st, 2nd, 3rd, and 4th weeks, followed by once-weekly (or every two weeks) dosing starting in the 6th week; 2) administering to the patient an injection in the 0th, 1st, 2nd, 3rd, and 4th weeks, followed by dosing every two weeks; and 3) administering to the patient an injection in the 0th, 1st, 2nd, 3rd, and 4th weeks, followed by once-weekly administration.

[0110] As used herein, the expression "formulated in a dosage amount to enable delivery of [the specified dosage] via [the route of administration]" means that a given pharmaceutical composition can be used to provide the desired dosage of an IL-17 antagonist, such as an IL-17 antibody, e.g., secukinumab, via a specified route of administration (e.g., SC or IV). By way of example, if the desired SC dosage is 300 mg, the clinician can use 2 ml of an IL-17 antibody formulation having a concentration of 150 mg / ml, 1 ml of an IL-17 antibody formulation having a concentration of 300 mg / ml, 0.5 ml of an IL-17 antibody formulation having a concentration of 600 mg / ml, etc. In each of these cases, these IL-17 antibody formulations are at a concentration high enough to enable subcutaneous delivery of the IL-17 antibody. Subcutaneous delivery typically requires delivery of a volume of about 2 ml or less, preferably about 1 ml or less. Preferred formulations are about 25 mg / mL to about 150 mg / mL secukinumab, about 10 mM to about 30 mM histidine (pH 5.8), about 200 mM to about 225 mM trehalose, about 0. A ready-to-use liquid pharmaceutical composition of 0.2% polysorbate 80 and from about 2.5 mM to about 20 mM methionine. It is a liquid pharmaceutical composition.

[0111] As used herein, the expression "a container having an IL-17 antagonist in an amount sufficient to enable delivery of [the specified dose]" means that a given container (e.g., a vial, a pen (pen), a syringe) can be used to provide the desired dose, and (e.g., as part of a pharmaceutical composition) contains a volume of IL-17 antagonist therein such that, for example, a clinician can use 2 ml from a container containing an IL-17 antibody formulation having a concentration of 150 mg / ml, 1 ml from a container containing an IL-17 antibody formulation having a concentration of 300 mg / ml, or 0.5 ml from a container containing an IL-17 antibody formulation having a concentration of 600 mg / ml, etc. In each such case, these containers have an amount of IL-17 antagonist sufficient to enable delivery of the desired 300 mg dose. As an example, if the desired dose is 300 mg then, a clinician can use 2 ml from a container containing an IL-17 antibody formulation having a concentration of 150 mg / ml, 1 ml from a container containing an IL-17 antibody formulation having a concentration of 300 mg / ml, or 0.5 ml from a container containing an IL-17 antibody formulation having a concentration of 600 mg / ml, etc. In each such case, these containers have an amount of IL-17 antagonist sufficient to enable delivery of the desired 300 mg dose. In some embodiments of the disclosed uses, methods, and kits, the dose of the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is about 300 mg, and the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is included in a liquid pharmaceutical formulation at a concentration of 150 mg / ml, and 2 ml of the pharmaceutical formulation is dispensed into two prefilled syringes, a pen-type syringe, or an autoinjector (each having 1 ml of the pharmaceutical formulation). In this case, the patient receives two 1-ml injections for a total dose of 300 mg during each administration. In some

[0112] In some embodiments of the disclosed uses, methods, and kits, the dose of the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is about 300 mg, and the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is included in a liquid pharmaceutical formulation at a concentration of 150 mg / ml, and 2 ml of the pharmaceutical formulation is dispensed into two prefilled syringes, a pen-type syringe, or an autoinjector (each having 1 ml of the pharmaceutical formulation). In this case, the patient receives two 1-ml injections for a total dose of 300 mg during each administration. In some cases, the patient receives two 1-ml injections for a total dose of 300 mg during each administration. In some cases, the patient receives two 1-ml injections for a total dose of 300 mg during each administration. In an embodiment, the dose of the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is, about 300 mg, and the IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof is, contained in a liquid pharmaceutical formulation at a concentration of 150 mg / ml, and 2 ml of the pharmaceutical formulation is dispensed into a self-injector or PFS. In this case, the patient receives a single injection of 2 ml for a total dose of 300 mg during each administration. Using a single injection of 2 ml (e.g., a single PFS or via a self-injector) method (i.e., a "single-dose preparation"), the drug exposure (AUC) and the maximum concentration (C max ) are equal to (similar to, i.e., within the range of acceptable variation according to the US FDA standard) the method using two injections of 1 ml (e.g., two PFSs or via two AIs) (i.e., a "repeated-dose preparation").

[0113] Disclosed herein is a method of treating hidradenitis suppurativa (HS), comprising subcutaneously (SC) administering to a patient in need thereof an IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof at a dose of about 300 mg to about 450 mg per week during weeks 0, 1, 2, and 3, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks), SC administering at a dose of about 300 mg to about 450 mg. Also disclosed herein is subcutaneously (SC) administering to a patient in need thereof an IL-17 antibody or an antigen-binding fragment thereof at a dose of about 300 mg to about 450 mg per week during weeks 0, 1, 2, and 3, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks), SC administering at a dose of about 300 mg to about 450 mg. 450 mg, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks), SC administering at a dose of about 300 mg to about 450 mg. An IL-17 antibody (e.g., secukinumab ) or an antigen-binding fragment thereof for use in treating HS, which comprises . Alternatively, disclosed herein is an IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof for use in the manufacture of a medicament for treating HS, which comprises administering subcutaneously (SC) to a patient in need thereof an IL-17 antibody or an antigen-binding fragment thereof at a dose of about 300 mg to about 450 mg per week for 0, 1, 2, and 3 weeks, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks) at a dose of about 300 mg to about 450 mg by SC administration. Disclosed herein is a method for treating hidradenitis suppurativa (HS), which comprises administering subcutaneously (SC) to a patient in need thereof an IL-17 antibody (e.g., secukinumab ) or an antigen-binding fragment thereof at a dose of about 300 mg to about 450 mg per week for 0, 1, 2, and 3 weeks, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks) at a dose of about 300 mg to

[0114] about 450 mg by SC administration, wherein the IL-17 antibody or an antigen-binding fragment thereof binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, and the epitope comprises Leu74, Tyr85, His86, Met87, Asn88, Val124 on one chain, Thr125, Pro126, Ile127, Val128, His129, and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, and wherein the IL-17 antibody has a K of about 100 - 200 pM when measured by a biosensor system (e.g., BIACORE) . D.D and the IL-17 antibody has an in vivo half-life of about 23 to about 30 days. Also disclosed herein are IL-17 antibodies or their antigen binding fragments at a dose of about 300 mg to about 450 mg per week during weeks 0, 1, 2, and 3, administered subcutaneously (SC) to a patient in need thereof, and then a) starting in week 4 and monthly (every 4 weeks); or b) starting in week 4 and every other week (every 2 weeks), at a dose of about 30 0 mg to about 450 mg, for use in treating HS, which is an IL-17 antibody (e.g., secukinumab) or its antigen binding fragment, where the IL-17 antibody or its antigen binding fragment binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, the epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 on one chain and Tyr43 , Tyr44, Arg46, Ala79, Asp80 on the other chain, where the IL-17 antibody has a K of about 100 - 200 pM as measured by a biosensor system (e.g., BIACORE®) and the IL-17 antibody has an in vivo half-life of about 23 to about 30 days. Alternatively, disclosed herein are pharmaceutical products for treating HS comprising administering an IL-17 antibody or its antigen binding fragment at a dose of about 300 mg to about 450 mg per week during weeks 0, 1, 2 and 3, subcutaneously (SC) to a patient in need thereof, and then a) starting in week 4 D and monthly (every 4 weeks); or b) starting in week 4 and every other week (every 2 weeks), at a dose of about 300 mg to about 450 mg, for use in treating HS, which is an IL-17 antibody (e.g., secukinumab) or its antigen binding fragment, where the IL-17 antibody or its antigen binding fragment binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, the epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 on one chain and Tyr43 , Tyr44, Arg46, Ala79, Asp80 on the other chain, where the IL-17 antibody has a K of about 100 - 200 pM as measured by a biosensor system (e.g., BIACORE®) and the IL-17 antibody has an in vivo half-life of about 23 to about 30 days, and further comprising administering, after the initial dosing, a) starting in week 4 and an IL-17 antibody (e.g., secukinumab) or an antigen-binding fragment thereof for use in the manufacture of a In this specification, the IL-17 antibody or antigen-binding fragment thereof is a polypeptide that binds to two mature IL-17 proteins. The antibody binds to an epitope on the IL-17 homodimer having one of the protein chains, Leu74, Tyr85, His86, Met87, Asn88, Val124 on the chain; Thr125, Pro126, Ile127, Val128, His129 and the other chain The above includes Tyr43, Tyr44, Arg46, Ala79, and Asp80, where IL-17 antibodies are measured by biosensor systems (e.g., BIACORE). When the K is about 100 to 200 pM, D and the IL-17 antibody has an It has an in vivo half-life of 0 days.

[0115] Disclosed herein is a method for treating hidradenitis suppurativa (HS), comprising administering to the patient a dose of 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, 2 IL-17 antibody (e.g., Selenite) at a dose of about 300 mg to about 450 mg every week for weeks 2 and 3. cukinumab) or an antigen-binding fragment thereof is administered subcutaneously (SC) to a patient in need thereof, thereafter, a) every month (every 4 weeks) beginning during the 4th week; or b) every other week beginning during the 4th week. and administering the same or similar compound SC to the patient (every two weeks) at a dose of about 300 mg to about 450 mg. wherein the IL-17 antibody or antigen-binding fragment thereof is: i) a polypeptide as set forth as SEQ ID NO: 8; Immunoglobulin V containing amino acid sequence H The domain and the amino acid sequence set forth as SEQ ID NO:10 Immunoglobulin V containing the acid sequence L Domain; ii) SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO: Immunoglobulin V containing the hypervariable region described as No. 3 HDomain and the immunoglobulin V containing the hypervariable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; L do main; or iii) the immunoglobulin V containing the hypervariable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 ; H Domain and the immunoglobulin V containing the hypervariable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. The present specification L also discloses an IL-17 antibody or an antigen-binding fragment thereof at a dose of about 300 mg to about 450 mg per week during weeks 0, 1, 2, and 3, subcutaneously (SC) administered to a patient in need thereof, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4 and administered SC at a dose of about 300 mg to about 450 mg every other week (every 2 weeks), which comprises an IL-17 antibody (such as secukinumab) or an antigen-binding fragment thereof for use in treating HS, wherein the IL-17 antibody or an antigen-binding fragment thereof is i) an immunoglobulin V domain containing the amino acid sequence described as SEQ ID NO: 8 and an immunoglobulin V domain containing the amino acid sequence described as SEQ ID NO: 10; ii) an immunoglobulin V domain containing the hypervariable regions described as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 ; H and an immunoglobulin V domain containing the hypervariable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; or iii) an immunoglobulin V domain containing the hypervariable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 ; L and an immunoglobulin V domain containing the hypervariable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. ; H domain and an immunoglobulin V containing the hypervariable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 ; L domain; or iii) an immunoglobulin V domain containing the hypervariable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 ; H domain and SEQ ID NO: 4, SEQ ID An immunoglobulin V domain containing the highly variable regions described as SEQ ID NO: 5 and SEQ ID NO: 6 L domain is included. Alternatively, disclosed herein is an IL-17 antibody or antigen-binding fragment thereof at a dose of about 30 0 mg to about 450 mg per week during weeks 0, 1, 2, and 3, administered subcutaneously (SC) to a patient in need thereof, followed by a) starting during week 4, monthly (every 4 weeks); or b) starting during week 4, every other week (every 2 weeks), at a dose of about 300 mg to about 450 mg for use in the manufacture of a medicament for treating HS, which is an IL-1 7 antibody (e.g., secukinumab) or antigen-binding fragment thereof, wherein the IL-17 antibody or antigen-binding fragment thereof comprises i) an immunoglobulin V domain comprising the amino acid sequence described as SEQ ID NO: 8 and an immunoglobulin V domain comprising the amino acid sequence described as SEQ ID NO: 10; ii) an immunoglobulin V H domain comprising the highly variable regions described as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 and an immunoglobulin V L domain comprising the highly variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; or iii) an immunoglobulin V domain comprising the highly variable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 and an immunoglobulin V H domain comprising the highly variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. domain; or iii) an immunoglobulin V L domain comprising the highly variable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 and an immunoglobulin V domain comprising the highly variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. H domain. In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg or about 450 mg. domain. In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg or about 450 mg. L domain is included.

[0116] In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg or about 450 mg. fragment is about 300 mg or about 450 mg.

[0117] In a preferred embodiment of the disclosed methods, uses, and kits, the IL-17 antibody or antigen-binding fragment thereof is administered subcutaneously at a dose of about 300 mg weekly during weeks 0, 1, 2, and 3, and then starting in week 4, and administered subcutaneously at a dose of about 300 mg once every week (every 2 weeks).

[0118] In another preferred embodiment of the disclosed methods, uses, and kits, the IL-17 antibody or antigen-binding fragment thereof is administered subcutaneously at a dose of about 300 mg weekly during weeks 0, 1, 2, and 3, and then starting in week 4, and administered subcutaneously at a dose of about 300 mg once every month (every 4 weeks).

[0119] In a preferred embodiment of the disclosed methods, uses, and kits, the patient achieves sustained response at 1 year of treatment as measured by the (Simplified) Hidradenitis Suppurativa Clinical Response (HiSCR), Numerical Rating Scale (NRS), Modified Sartorius HS Score, Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA), or Dermatology Life Quality Index (DLQI).

[0120] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has been previously treated with systemic agents for HS prior to treatment with the IL-17 antibody or antigen-binding fragment. In a preferred embodiment of the disclosed methods, uses, and kits, the systemic agents are topical treatment, antibiotics ​​​​​​​​​​​​​ selected from the group consisting of a substance, an immunosuppressant, a TNF-α inhibitor, an IL-1 antagonist, and combinations thereof.

[0121] In some embodiments of the disclosed methods, uses, and kits, the patient has not been previously treated with a systemic agent or topical treatment for HS prior to treatment with an IL-17 antibody or antigen-binding fragment.

[0122] In preferred embodiments of the disclosed methods, uses, and kits, the IL-17 antibody or antigen-binding fragment is administered in combination with at least one of a TNF-α inhibitor, an antibiotic, an IL-1 inhibitor, or an immunosuppressant.

[0123] In preferred embodiments of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg. In other preferred embodiments of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 450 mg.

[0124] In preferred embodiments of the disclosed methods, uses, and kits, the patient has moderate to severe HS.

[0125] In preferred embodiments of the disclosed methods, uses, and kits, the patient is an adult. In some embodiments of the disclosed methods, uses, and kits, the patient is a young adult.

[0126] In preferred embodiments of the disclosed methods, uses, and kits, the IL-17 antibody or antigen-binding fragment is formulated in a pharmaceutical preparation, wherein the pharmaceutical preparation further comprises a buffer and a stabilizer. In some embodiments of the disclosed methods, uses, and kits, the pharmaceutical preparation is a liquid. ​​​​​​​​​​​is in a form. In some embodiments of the disclosed methods, uses, and kits, the pharmaceutical formulation is in lyophilized form. In some embodiments of the disclosed methods, uses, and kits, the pharmaceutical formulation is dispensed into a prefilled syringe, vial, pen-type syringe, or autoinjector .

[0127] In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical formulation is dispensed into a means for administration selected from the group consisting of a prefilled syringe, pen-type syringe, and autoinjector, and said means is dispensed in a kit, and the kit further comprises instructions for use.

[0128] In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical formulation is dispensed into an autoinjector or prefilled syringe , and the autoinjector or prefilled syringe is dispensed in a kit, and the kit further comprises instructions for use.

[0129] In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical formulation is dispensed into an autoinjector or prefilled syringe , the autoinjector or prefilled syringe is dispensed in a kit, and the kit further comprises instructions for use.

[0130] In a preferred embodiment of the disclosed methods, uses, and kits, the dose of the IL-17 antibody or antigen-binding fragment is about 450 mg, and the pharmaceutical formulation is dispensed into an autoinjector or prefilled syringe Distributed within the kit, the autoinjector or prefilled syringe is distributed within the kit, and the kit further includes instructions for use.

[0131] In a preferred embodiment of the disclosed methods, uses, and kits, the dose is 300 mg which is administered as a single subcutaneous dose of 2 ml from a formulation comprising an IL-17 antibody or antigen-binding fragment at 150 mg / ml wherein the pharmacologic exposure of the patient to the IL-17 antibody or antigen-binding fragment is equal to the pharmacologic exposure of the patient to the IL-17 antibody or antigen-binding fragment using two separate subcutaneous doses of 1 ml each of the same formulation.

[0132] In a preferred embodiment of the disclosed methods, uses, and kits, the dose is 300 mg which is administered as two separate subcutaneous doses of 1 ml each from a formulation comprising an IL-17 antibody or antigen-binding fragment at 150 mg / ml.

[0133] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a HS-PGA score of ≧3 prior to treatment with the IL-17 antibody or antigen-binding fragment. In some embodiments, the patient is selected for treatment based on having a HS-PGA score of ≧3.

[0134] In a preferred embodiment of the disclosed methods, uses, and kits, the patient is classified as Hurley stage II or III prior to treatment with the IL-17 antibody or antigen-binding fragment. In some embodiments, the patient is selected for treatment based on being classified as Hurley stage II or III.

[0135] ​​​​​​In a preferred embodiment of the disclosed methods, uses, and kits, patients achieve (simplified) HiSCR by week 16 of treatment.

[0136] In a preferred embodiment of the disclosed methods, uses, and kits, patients achieve NRS30 by week 16 of treatment.

[0137] In a preferred embodiment of the disclosed methods, uses, and kits, patients have a reduction in HS erythema by week 16 of treatment.

[0138] In a preferred embodiment of the disclosed methods, uses, and kits, patients achieve a decrease of ≤ 6 as measured by DLQI by week 16 of treatment.

[0139] In a preferred embodiment, when the disclosed method, use, or kit is used to treat a population of patients with moderate to severe HS, at least 51% of said patients achieve simplified HiSCR by week 16 of treatment in response to the foregoing administration step.

[0140] In a preferred embodiment, when the disclosed method, use, or kit is used to treat a population of patients with moderate to severe HS, at least 40% of said patients achieve an NRS30 response by week 16 of treatment in response to the foregoing administration step.

[0141] In a preferred embodiment, when the disclosed method, use, or kit is used to treat a population of patients with moderate to severe HS, less than 15% of said patients experience HS erythema during 16 weeks of treatment in response to the foregoing administration step.

[0142] In a preferred embodiment of the disclosed methods, uses, and kits, the patient does not have extensive scarring as a result of HS (fewer than 20 fistulas) prior to treatment with an IL-17 antibody or an antigen-binding fragment thereof. In some embodiments, the patient is selected for treatment based on not having extensive scarring as a result of HS (fewer than 20 fistulas). In a preferred embodiment of the disclosed methods, uses, and kits, the patient is further treated with at least one topical drug therapy and at least one antiseptic in combination with an IL-17 antibody or an antigen-binding fragment thereof. In a preferred embodiment of the disclosed methods, uses, and kits, the patient is treated with an IL-17 antibody or an antigen-binding fragment thereof for at least one year.

[0143] In a preferred embodiment of the disclosed methods, uses, and kits, the patient experiences rapid pain relief, measured by VAS or NRS, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof. In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a rapid decrease in CRP, measured using standard CRP measurements, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof. In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment.

[0144] In a preferred embodiment of the disclosed methods, uses, and kits, the patient is treated with an IL-17 antibody or an antigen-binding fragment thereof for at least one year. In a preferred embodiment of the disclosed methods, uses, and kits, the patient experiences rapid pain relief, measured by VAS or NRS, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof.

[0145] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a rapid decrease in CRP, measured using standard CRP measurements, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof. In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment. In a preferred embodiment of the disclosed methods, uses, and kits, the patient experiences rapid pain relief, measured by VAS or NRS, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof.

[0146] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a rapid decrease in CRP, measured using standard CRP measurements, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof. In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment. In a preferred embodiment of the disclosed methods, uses, and kits, the patient experiences rapid pain relief, measured by VAS or NRS, as early as one week after the first administration of an IL-17 antibody or an antigen-binding fragment thereof.

[0147] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment. In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment.

[0148] In a preferred embodiment of the disclosed methods, uses, and kits, the patient has a decrease in the modified Sartorius score by 16 weeks of treatment. It has an improvement in DLQI.

[0149] In a preferred embodiment of the present disclosure, the IL-17 antibody or its antigen-binding fragment is a monoclonal antibody.

[0150] In a preferred embodiment of the present disclosure, the IL-17 antibody or its antigen-binding fragment is a human or humanized antibody.

[0151] In a preferred embodiment of the present disclosure, the IL-17 antibody or its antigen-binding fragment is a human antibody there is.

[0152] In a preferred embodiment of the disclosed method, use, and kit, the IL-17 antibody or antigen-binding fragment is a human monoclonal antibody.

[0153] In a preferred embodiment of the present disclosure, the IL-17 antibody or its antigen-binding fragment is an IgG1 subclass of human antibody.

[0154] In a preferred embodiment, the IL-17 antibody or its antigen-binding fragment has a κ light chain.

[0155] In a preferred embodiment of the present disclosure, the IL-17 antibody or its antigen-binding fragment is an IgG1 κ-type human antibody.

[0156] In a preferred embodiment of the disclosed method, use, and kit, the IL-17 antibody or antigen-binding fragment has a T of about 7 to 8 days max have.

[0157] In a preferred embodiment of the disclosed method, use, and kit, the IL-17 antibody or antigen-binding fragment has an absolute bioavailability of about 60% to about 80%.

[0158] In a preferred embodiment of the present disclosure, the IL-17 antibody or an antigen-binding fragment thereof is secukinumab umab.

[0159] Kit The present disclosure also encompasses a kit for treating HS. Such a kit comprises an IL-17 antagonist, such as an IL-17 binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof, such as secukinumab), or an IL-17 receptor binding molecule (e.g., an IL-17 antibody or an antigen-binding fragment thereof) (e.g., in liquid or lyophilized form), or a pharmaceutical composition comprising an IL-17 antagonist as described above. Further, such a kit can include means for administering the IL-17 antagonist (e.g., an autoinjector, syringe and vial, prefilled syringe, prefilled pen) and instructions for use. These kits can contain, for treating HS, an additional HS therapeutic agent (as described above) for delivery in combination with an encapsulated IL-17 antagonist, such as an IL-17 binding molecule, such as an IL-17 antibody, such as secukinumab. Such kits can also include instructions for administering an IL-17 antagonist (e.g., an IL-17 antibody, such as secukinumab) for treating HS patients. Such instructions can provide a dosage (e.g., 10 mg / kg, 300 mg, 450 mg), a route of administration (e.g., IV, SC), and a dosing regimen (e.g., weekly, monthly, monthly after weekly, alternate weeks after weekly) for use in combination with an encapsulated IL-17 antagonist, such as an IL-17 binding molecule, such as an IL-17 antibody, such as secukinumab.

[0160] The term "means for administration" is used to denote, without limitation, any available means for systemic administration of a drug to a patient, including but not limited to prefilled syringes, vials, syringes, pen injectors, autoinjectors, intravenous drip bags, pumps, etc. Using such means, a patient can self-administer (i.e., administer without the assistance of a physician) the drug, or a physician can administer the drug. In some embodiments, a total dose of 300 mg is delivered in a total volume of 2 ml distributed into two PFSs or autoinjectors each containing a 1 ml volume of an IL-17 antibody at 150 mg / ml, such as secukinumab. In this case, the patient receives two 1 ml injections (a repeated dose formulation). In a preferred embodiment, a total dose of 300 mg is delivered in a total volume of 2 ml of an IL-17 antibody at 150 mg / ml, such as secukinumab, distributed into a single PFS or autoinjector. In this case, the patient receives one 2 ml injection (a single dose formulation). Disclosed herein is a kit for use in treating a patient having HS, comprising an IL-17 antagonist (e.g., an IL-17 binding molecule, e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) and a means for administering the IL-17 antagonist to the HS patient. In some embodiments, the kit further comprises instructions for administration of the IL-17 antagonist, where the instructions state that the IL-17 antagonist (e.g., an IL-17 binding molecule, e.g., an IL-17 antibody or an antigen-binding fragment thereof, e.g., secukinumab) is

[0161] ​​​​​​​​​​​​​1) During weeks 0, 1, 2, and 3, weekly, at about 300 mg to about 450 mg (e.g., about 300 mg, or about 450 mg), by SC, and then, a) Starting in week 4, monthly (every 4 weeks); or b) Starting in week 4, every other week (every 2 weeks), at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg), by SC, 2) During weeks 0, 2, and 4, every other week, at about 3 mg / kg to about 10 mg / kg (e.g., about 3 mg / kg, about 10 mg / kg), by IV, and then, a) Starting in week 8, monthly (every 4 weeks); or b) Starting in week 6, every other week (every 2 weeks), at about 300 mg to about 450 mg (e.g., about 300 mg, about 450 mg), by SC, It is shown that it should be administered to the patient.

[0162] General In the most preferred embodiments of the disclosed uses, methods, and kits, the IL-17 antagonist is an IL-17 antibody or an antigen-binding fragment thereof. In some embodiments of the disclosed uses, methods, and kits , the IL-17 antibody or an antigen-binding fragment thereof is selected from the group consisting of: a) an IL-17 antibody or an antigen-binding fragment thereof that binds to an epitope of human IL-17 comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129; b) an IL-17 antibody or an antigen-binding fragment thereof that binds to an epitope of human IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80; c) an epitope of an IL-17 homodimer having two mature human IL-17 protein chains (said epitope is ), an IL-17 antibody or an antigen-binding fragment thereof that binds to the epitope; b ) an IL-17 antibody or an antigen-binding fragment thereof that binds to an epitope of human IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80; c) an epitope of an IL-17 homodimer having two mature human IL-17 protein chains (said epitope is ), an IL-17 antibody or an antigen-binding fragment thereof that binds to the epitope; c) an epitope of an IL-17 homodimer having two mature human , Leu74, Tyr85, His86, Met87, Asn88, Val on one chain 124, Thr125, Pro126, Ile127, Val128, His129, and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain); An IL-17 antibody or an antigen-binding fragment thereof that binds to; d) An epitope of an IL-17 homodimer having two mature human IL-17 protein chains (the epitope is on one chain Leu74, Tyr85, His86, Met87, Asn88, Val124, Th r125, Pro126, Ile127, Val128, His129, and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain); An IL-17 antibody or an antigen-binding fragment thereof that binds to (wherein the IL-17 antibody or an antigen-binding fragment thereof has a K of about 100-200 pM, and the IL-17 antibody or an antigen-binding fragment thereof has an in vivo half-life of about 23 to about 35 days); e) An epitope of an IL-17 homodimer having two mature IL-1 7 protein chains (the epitope is on one chain D Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129, and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain); An IL-17 antibody that binds to (wherein the IL-17 antibody has a K of about 100-200 pM when measured by a biosensor system (e.g., Bi acore (registered trademark)), and the IL-17 antibody has an in vivo half-life of about 23 to about 30 days); ; D has and the IL-17 antibody has an in vivo half-life of about 23 to about 30 days); and f) an IL-17 antibody or an antigen-binding fragment thereof comprising: i) an immunoglobulin heavy chain variable domain (V ) comprising the amino acid sequence described as SEQ ID NO: 8 H ; ii) an immunoglobulin light chain variable domain (V ) comprising the amino acid sequence described as SEQ ID NO: 10 L ; iii) an immunoglobulin V domain comprising the amino acid sequence described as SEQ ID NO: 8 and an immunoglobulin V H domain comprising the amino acid sequence described as SEQ ID NO: 1 0; iv) an immunoglobulin V L domain comprising the high-frequency variable regions described as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 H ; v) an immunoglobulin V domain comprising the high-frequency variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 ; vi) an immunoglobulin V L domain comprising the high-frequency variable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 1 3; vii) an immunoglobulin V H domain comprising the high-frequency variable regions described as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 and an immunoglobulin V H domain comprising the high-frequency variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 ; viii) an immunoglobulin V L domain comprising the high-frequency variable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 and an immunoglobulin V H domain comprising the high-frequency variable regions described as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 L ; ix) an immunoglobulin light chain comprising the amino acid sequence described as SEQ ID NO: 14; x) an immunoglobulin heavy chain comprising the amino acid sequence described as SEQ ID NO: 15; or xi) An immunoglobulin light chain comprising the amino acid sequence described as SEQ ID NO: 14, and SEQ ID NO: 15 An immunoglobulin heavy chain comprising the amino acid sequence described as such.

[0163] In the most preferred embodiments of the disclosed methods, kits, or uses, the IL-17 antibody or its antigen-binding fragment is a monoclonal antibody. In the most preferred embodiments of the disclosed methods, kits, or uses, the IL-17 antibody or its antigen-binding fragment is a human or humanized antibody, preferably a human antibody. In the most preferred embodiments of the disclosed methods, kits, or uses the IL-17 antibody or its antigen-binding fragment is a human antibody of the IgG1 isotype. In the most preferred embodiments of the disclosed methods, kits, or uses, the antibody or its antigen-binding fragment is secukinumab.

[0164] In the most preferred embodiments of the disclosed methods, kits, or uses, the antibody or its antigen-binding fragment is secukinumab, the dose size is constant (also referred to as a "fixed" dose, which is different from dosing based on body weight or body surface area), the dose is 300 mg, the administration route is SC, and the regimen is administration at weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, etc. (weekly during weeks 0, 1, 2, and 3, then starting at week 6, every other week).

[0165] Details of one or more embodiments of the present disclosure are described in the accompanying description above. All methods and materials similar or equivalent to those described in this specification can be used in the practice or testing of the present disclosure, but the preferred methods and materials are described herein. Other features, objects, and advantages of the present disclosure will be apparent from this description and the claims. This specification and ​​​​​​In the appended claims, the singular forms include the plural reference unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited herein are incorporated by reference. The following examples are given to illustrate more specifically the preferred embodiments of the present disclosure. These examples should in no way be construed as limiting the scope of the disclosed subject matter as defined by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited herein are incorporated by reference. The following examples are given to illustrate more specifically the preferred embodiments of the present disclosure. These examples should in no way be construed as limiting the scope of the disclosed subject matter as defined by the appended claims.

Examples

Example

[0166] Example 1: Initial study of anti-IL-17 antibody in the treatment of HS Initial clinical evidence of the effect of the anti-IL-17 antibody, CJM112, supports the potential of anti-IL-17 antibodies as an effective treatment for patients with HS. Like secukinumab, CJM112 is an Ig G1 / κ isotype recombinant full human anti-interleukin-17A monoclonal antibody developed for the potential treatment of autoimmune and inflammatory conditions. CJM112 binds to human homodimeric IL-17A with a higher affinity (6 pM) than secukinumab and inactivates the biological activity of IL-17A in vitro. This Phase 2 study (CCJM112X2202) was a randomized, placebo-controlled, double-blind, multi-center study with two periods in parallel groups of patients with moderate to severe chronic HS in the USA, Denmark, Switzerland, Germany, and the Netherlands. This study involved approximately 4

[0167] This Phase 2 study (CCJM112X2202) was conducted in the USA, Denmark, Switzerland, Germany, and the Netherlands, and was a randomized, placebo-controlled, double-blind, multi-center study with two periods in parallel groups of patients with moderate to severe chronic HS. ​​​​​​​​A weekly screening period, two consecutive treatment periods of 16 weeks (Period 1 and Extension Period 2), and an approximately 12-week follow-up (without treatment) were included. Patients were randomly assigned in a 2:1:1 ratio to one of the following three treatment sequences: · Treatment Sequence 1: CJM112 300 mg (s.c.) in Period 1; placebo (s.c.) in Extension Period 2 · Treatment Sequence 2: placebo (s.c.) in Period 1; CJM112 50 mg (s.c.) in Extension Period 2 · Treatment Sequence 3: placebo (s.c.) in Period 1; CJM112 300 mg (s.c.) in Extension Period 2

[0168] During each treatment period, patients were administered a total of 10 times. The study drug was administered subcutaneously (s .c.) at the clinical facility. The investigational drug CJM112 150 mg / ml and a matching placebo were provided in glass vials (each containing 150 mg of CJM112 or placebo as a liquid). During each treatment period, the first 5 administrations were performed weekly, followed by 5 bi-weekly administrations.

[0169] The selected primary endpoint was based on the clinical response rate (defined as a 2-point decrease from baseline in the Hidradenitis Suppurativa-Physician Global Assessment (HS PGA) score). The HS-PGA score is a 6-point scale of static overall severity described in Kimball et al 2012 Ann Intern Med 157:846-855.

[0170] ​​​​​ Adult male and female patients with chronic HS diagnosed clinically (prior to screening) for at least 1 year who had received prior antibiotic therapy The study population consisted of adult male and female patients with chronic HS diagnosed clinically (prior to screening) for at least 1 year who had received prior antibiotic therapy and had a baseline HS-PGA score of at least moderate severity (score of 3 or greater on a 6-point scale), at least 4 inflammatory pustules and / or inflammatory nodules (AN) present in at least 2 different anatomical regions, and at least 1 region that was at least baseline Hurley stage II (moderate). A maximum of 25 draining fistulas were allowed for baseline eligibility. At least moderate severity (score of 3 or greater on a 6-point scale) of HS-PGA score on baseline At least 4 inflammatory pustules and / or inflammatory nodules (AN) present in at least 2 different anatomical regions And at least 1 region was at least baseline Hurley stage II (moderate). A maximum of 25 draining fistulas were allowed for baseline eligibility. Furthermore, the weight had to be between 50 and 150 kg.

[0171] Furthermore, the weight had to be between 50 and 150 kg.

[0172] Exclusion criteria included previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment. If spironolactone or other antiandrogens (such as finasteride, cyproterone acetate) were used (for HS), only patients who had used a stable dose for the past 3 months and were planned to continue during the study period were eligible. Patients with a history of severe systemic candidal infection, or evidence of candidiasis within 2 weeks prior to randomization, and patients with active systemic or skin infections (other than colds or HS-related) within 2 weeks before randomization / first treatment were excluded. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. Previous treatment with biologics that block IL-17 or IL-17R (including secukinumab, ixekizumab, and brodalumab), recent use of other biologics (e.g., adalimumab within the past 3 months), use of any systemic treatment for HS within the 4 weeks immediately prior to randomization (such as retinoids or other immunomodulators), or use of systemic antibiotics for HS during the last week before randomization / first treatment were included. There was a need. Additional exclusion criteria were duly applied. Topical antibiotics and antiseptics, and standard wound management were permitted throughout the study. Oral antibiotics could be used as emergency treatment for skin infections but should not be used for more than 2 weeks. .

[0173] A total of 66 subjects were enrolled and randomly assigned in Period 1 (33 in the CJM112 300 mg group and 33 in the placebo group), of which 60 patients (90.9%) (29 in the CJM 112 300 mg group and 31 in the placebo group) completed Week 16 in Period 1. A total of 6 patients discontinued the study prior to Week 16. Reasons for discontinuation were “dropout from follow-up,” “adverse event” (cystitis in the CJM112 group), and “patient / caregiver decision.”

[0174] The primary endpoint was to determine the efficacy of CJM112 300 mg in HS patients by using the clinical responder rate at Week 16 (the end of Period 1) compared to placebo. For this purpose, the responder rate of HS-PGA (Hidradenitis Suppurativa - Physician Global Assessment), defined as at least a 2-point decrease from baseline on a 6-point scale (see Kimball 2012), was used. . The responder rate of HS-PGA is shown in Figure 1 and compared the treatments at Week 16 using Bayesian statistics (Table 4).

[0175] .

[0176] [Table 4]

[0177] The percentage of patients reaching this evaluation item in the 16th week (HS-PGA responder rate) was 12.5% (or 4 out of 32) in the placebo compared to 32.3% responders (or 10 out of 31) with anti-IL17 treatment. The posterior probability in support of CJM112 was 0.9 7, indicating that this may reflect a true effect.

[0178] The primary evaluation item of this study was slightly different from that of a previous Phase 2 study using HUMIRA (Kimball et al 2012 Ann Intern Med 157:846-855). The same 6-point HS-PGA score was used, but the definition of responders differed between the studies. Kimball used a more stringent and composite definition requiring a 2-point decrease from baseline and a problem-free / minimal / mild stage at the 16th week to achieve responder status.

[0179] For comparison purposes, the inventors calculated the responder rate score cores using the "Kimball 2012" definition. In the CJM112 group, 6 out of 31 patients responded (19.4%) compared to only 2 out of 32 patients (6.3%) in the placebo treatment group. This is comparable to what adalimumab achieved in the Phase 2 study (Table 5).

[0180]

Table 5

[0181] ​​​​In addition to the primary endpoint (HS-PGA), there was a numerical reduction in inflammatory lesions, primarily inflammatory nodules. A small number of patients were observed in both treatment groups, i.e., CJM112 and placebo, and the CJM112 group The magnitude of the treatment effect was similar to that observed with adalimumab. (In CJM112, the inflammatory lesions were -2.6 compared to placebo, and For darimumab, the mean mean score was -2.4 to -3.0 compared to placebo. However, the mean mean score was 0.05, and the mean mean score was 0.02. The treatment effect on reducing schizophrenia was not statistically significant in this small phase 2 study.

[0182] Clinical relevance of effects on inflammatory lesion counts observed in a phase 2 study of CJM112 To better understand the data, we compared them with publicly available data for adalimumab. Absolute lesion count results are only publicly available from phase 3 studies. EER 1 is closer to the CJM112 Phase 2 study and shows a more severe cluster of disease than PIONEER 2. We use the Pioneer 1 for the comparison below.

[0183] [Table 6]

[0184] The CJM112 Phase 2 study population was larger at baseline than the PIONEER 1 study Although most patients had a high number of inflammatory lesions, the magnitude of observed change in inflammatory lesion counts during the study was The results were similar between the placebo arms of both studies, which is consistent with the results of the Phase 2 study of CJM112. The panel was representative of the moderate to severe HS population behaving within the expected variability during the study. This confirmed the above.

[0185] The therapeutic effects of adalimumab and CJM112 were mainly observed in inflammatory variables, and the size with CJM112 was slightly larger than that with adalimumab. In both studies, only a little therapeutic effect was observed in abscesses and discharging fistulas. Consistent results were also observed in PIONEER 2 (Kimball et al 2016a N Engl J Med;375(5):422-434). Even with the use of a relatively high dose of an IL-17 blocker (initially, five doses of 300 mg of CJM112 were administered weekly, followed by five biweekly administrations), no significant clinical safety signals were detected. The severity of most AEs was mild or moderate. Overall, infections were as frequent in the active ingredient group as in the placebo treatment group, but some infections occurred more frequently in patients treated with CJM112 (pharyngitis, upper respiratory tract infection, cystitis, etc.). Adverse events differed in frequency between the groups, but it is not recognized that a small number of patients can be judged as this relatively small group. Serious adverse events were only observed during the placebo treatment period and were considered unrelated (angina and abscess). The latter occurred approximately 23 weeks after the last dose of CJM112 and was hospitalized for the removal of an HS abscess. No new or unanticipated safety signals were detected in the HS population after treatment with the high-affinity anti-IL-17A antibody, CJM112. Example 2

[0186] Despite the use of a relatively high dose of an IL-17 blocker (initially, five doses of 300 mg of CJM112 were administered weekly, followed by five biweekly administrations), no significant clinical safety signals were detected. The severity of most AEs was mild or moderate. Overall, infections were as frequent in the active ingredient group as in the placebo treatment group, but some infections occurred more frequently in patients treated with CJM112 (pharyngitis, upper respiratory tract infection, cystitis, etc.). Adverse events differed in frequency between the groups, but it is not recognized that a small number of patients can be judged as this relatively small group. Serious adverse events were only observed during the placebo treatment period and were considered unrelated (angina and abscess). The latter occurred approximately 23 weeks after the last dose of CJM112 and was hospitalized for the removal of an HS abscess.

[0187] No new or unanticipated safety signals were detected in the HS population after treatment with the high-affinity anti-IL-17A antibody, CJM112.

[0188] ​​​​​​​​​​​​​Example 2A: Predicting responder rates in heavy subjects for secukinumab at higher dosing (450mg) and more frequent dosing (Q2w) Predicting responder rates in heavy subjects for secukinumab The objective of the modeling and simulation (M&S) work in this example was to investigate the simulated efficacy of secukinumab in heavy subjects after the two higher dosing regimens mentioned above (450 Q4W and 300 Q2W). The inventors herein report a modeling and simulation (M&S) work wherein they investigated the responder rates of PASI 75 and PASI 90 in patients ≥ body weight 90 kg using the standard regimen of secukinumab in psoriasis, i.e., 300mg Q4W, compared to the predicted responses using the higher dosing regimens, i.e., 450mg Q4W or 300mg Q2W. The main objective of this work was to use the reaction rates predicted by the model (i.e., simulated) to estimate the magnitude of improvement using higher doses in heavier patients. This analysis used PASI data from studies CAIN457A2302 and CAIN457A2303 up to week 52. Only subjects ≥ 90 kg (n = 641) were used for model building. This data included responses from both the 150mg and 300mg regimens in patients who were initially treated with placebo up to week 12 and then randomly assigned to 150mg or 300mg

[0189] . The binary outcome, either PASI 75 or PASI 90, was modeled as a function of serum secukinumab concentration. An indirect response model was used due to the time lag between response and concentration . All measurements up to week 52 were used . ​​​​​, which was used in this model. It was calculated from the post-estimates of the pharmacokinetic (PK) model of the previously developed secukinumab population using the predicted concentrations at the time of PASI measurement. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here.

[0190] Briefly, this model was a two-compartment model that used body weight as a covariate for first-order absorption and the central clearance (CL), the distribution volumes of the central and peripheral compartments (V2 and V3), and the inter-compartment clearance (Q). The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here. The post-estimates for the PK model parameters for patients in A2302 and A2303 were used as inputs to the pharmacodynamic (PD) modeling. Previous modeling attempts for secukinumab in psoriasis included population PK / PD models for continuous PASI scores. However, this model had some limitations (e.g., slight overprediction during the induction period) in representing the PASI 75 responder rate, which was more evident for more extreme response thresholds such as PASI 90. Covariate exploration (such as baseline PASI or body weight) was also previously investigated and found not to improve model fit. Therefore, covariate exploration was not performed here.

[0191] The two components of the population model are a structural model that describes the systematic trends in the data and the mechanisms that give rise to these trends as far as possible; and a random effects model that describes the between-subject and within-subject variability for these trends. In this analysis, the components of the model were selected and assembled based on a combination of decision-making derived from data, guided by previous knowledge, the modeling experience of the PASI response of secukinumab, and statistical and discovery rules. The two components of the population model are a structural model that describes the systematic trends in the data and the mechanisms that give rise to these trends as far as possible; and a random effects model that describes the between-subject and within-subject variability for these trends. In this analysis, the components of the model were selected and assembled based on a combination of decision-making derived from data, guided by previous knowledge, the modeling experience of the PASI response of secukinumab, and statistical and discovery rules. The two components of the population model are a structural model that describes the systematic trends in the data and the mechanisms that give rise to these trends as far as possible; and a random effects model that describes the between-subject and within-subject variability for these trends. In this analysis, the components of the model were selected and assembled based on a combination of decision-making derived from data, guided by previous knowledge, the modeling experience of the PASI response of secukinumab, and statistical and discovery rules. The two components of the population model are a structural model that describes the systematic trends in the data and the mechanisms that give rise to these trends as far as possible; and a random effects model that describes the between-subject and within-subject variability for these trends. In this analysis, the components of the model were selected and assembled based on a combination of decision-making derived from data, guided by previous knowledge, the modeling experience of the PASI response of secukinumab, and statistical and discovery rules. The two components of the population model are a structural model that describes the systematic trends in the data and the mechanisms that give rise to these trends as far as possible; and a random effects model that describes the between-subject and within-subject variability for these trends. In this analysis, the components of the model were selected and assembled based on a combination of decision-making derived from data, guided by previous knowledge, the modeling experience of the PASI response of secukinumab, and statistical and discovery rules. This analysis utilized the NONMEM software system, NONMEM version 7.3.0 (Icon Development Solutions, Ellicot City, MD, USA), which is accessed from GPSII and runs on a MODESIM high-performance computer processing environment. For automation of execution, Perl-speaks-NONMEM 4.2.0 was used. All model building was carried out using the Laplace method. This analysis was performed to estimate population parameters (mean and between-subject variability). After browsing the model diagnostics, the final (best) model was selected based on the likelihood and Bayesian Information Criteria (BIC). Simulations were used to predict the PASI 75 or PASI 90 responder rate using the best model. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. 7.3.0(Icon Development Solutions,Ellicot t City,MD,USA) was used for this implementation. Perl-speaks-NONMEM 4.2.0 was used for automated execution. All model construction was carried out using the Laplace method. This analysis was performed to estimate population parameters (mean and between-subject variability). peaks-NONMEM 4.2.0 was used. All model building was performed using the Laplace method. This analysis was conducted to estimate population parameters (average and variability between subjects). This analysis was carried out using the Laplace method to estimate population parameters (mean and between-subject variability). )

[0192] After browsing the model diagnostics, the final (best) model was selected based on the likelihood and Bayesian Information Criteria (BIC). Simulations were used to predict the PASI 75 or PASI 90 responder rate using the best model. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. For each regimen (i.e., 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W), 1000 replicates were created using the ONLYSIMULATION option of NONMEM. Simulations were created using the final estimated values for the fixed-effect parameters (i.e., emax, ec50, kout, gamma, and alpha), as well as the inter-individual variability for sampling. The PASI 75 or PASI 90 binary response was simulated by extracting from a binary distribution with probabilities determined from this model. The source dataset for the simulations was the same dataset used when establishing the model, i.e., the dataset used when using subjects with body weight ≥ 90 kg, and it included the post hoc PK estimated values of the subjects. Regular for 300 mg Q4W, 300 mg Q2W, and 450 mg Q4W dosing schedules (weekly until week 4, then every 4 weeks for Q4W or every 2 weeks for Q2W until week 52) were included in the simulation dataset together with a regular sampling schedule (i.e., weekly until week 12 and then every 4 weeks). For each simulation replicate and at each time point, the predicted responder rate was calculated. From 1 000 runs, the median and 95% prediction intervals for the responder rate were determined.

[0193] Figure 2 shows the simulated PASI 90 responder rates for different regimens in subjects with a body weight of 90 kg or more. Table 7 contains the predicted responder rates for PASI 75 and PASI 90 at weeks 1 2, 16, and 52 for different regimens.

[0194]

Table 7

[0195] In the simulation, higher responder rates (for PASI 75 or PASI 90) in heavier subjects are predicted to be the result of either a higher dosing regimen, 300 mg Q2W or 450 mg Q4W, compared to the standard 300 mg Q4W regimen. This simulation suggests that the responder rates at week 16 will be similar for any of the higher dosing regimens (91% for PASI 75 and 76% for PASI 90, see Table 7). However, compared to 450 mg Q4W, the 300 mg Q2W regimen gives a higher response rate from week 20 ​​​​ is predicted. By week 52, after 300 mg Q2W vs 450 mg Q4W the median responder rates are predicted to be 99% vs 96% for PASI 75 and 93% vs 87% for PASI 90 (see Table 7).

[0196] Based on this information, HS patients who tend to be heavier and have deep tissue disease are expected to benefit from more frequent dosing of secukinumab or higher doses of secukinumab.

[0197] Example 2B: Modeling and Simulation of Secukinumab Dose Response in Heavier Patients and Simulation The modeling and simulation in this example consists of week 52 data from the secukinumab OPTIMIZE study. OPTIMIZE (NCT02409667) was a randomized, multi-center, open-label, 52-week, comparator-controlled trial to evaluate the efficacy, safety, and tolerability of secukinumab 300 mg (SC) in the long-term treatment optimization of patients with moderate to severe chronic plaque-type psoriasis. In this study, patients who were sub-optimal responders at week 24, i.e., those who reached PASI 75 (i.e., a 75% decrease from baseline PASI score) but not PASI 90 after 24 weeks on secukinumab 300 mg q4w, were subsequently randomly assigned to either secukinumab 300 mg q4w or secukinumab 300 mg q2w (up to week 52).

[0198] The upper panel in Figure 5 shows, for that partial subgroup, the treatment group (q2w or q4w) And the percentage of responders (PASI90, i.e., patients who achieved a 90% reduction from baseline in PASI score at week 52) for each weight classification (<90 or >90 kg) is shown 2. The lower panel represents the secukinumab trough concentration at week 52 (given as mcg / mL) in the same subgroups .. In the simulation, heavier patients (>90 kg) are shown to benefit in terms of both exposure and efficacy from being administered 300 mg Q2W

[0199] . The PASI% response indicates that higher antibody concentrations improve efficacy in patients >90 kg However, the same is not seen in patients <90 kg. The data suggest that efficacy in psoriasis patients is maximized at approximately >30 mcg / mL (PASI 90 - 60%). Based on this information, HS patients who tend to be heavier and have deep tissue disease are expected to benefit from more frequent dosing of secukinumab . (PASI 90 - 60%). Based on this information, HS patients who tend to be heavier and have deep tissue disease are expected to benefit from more frequent dosing of secukinumab . . .

[0200] Example 3: Efficacy and safety of secukinumab in adult patients with moderate to severe HS The following Table 8 describes the details of the clinical trial design to demonstrate the efficacy of two secukinumab dosing regimens compared to placebo by assessing the percentage of subjects who reached HiSCR after 16 weeks of treatment . . .

[0201]

Table 8

[0202]

Table 9

[0203]

Table 10

[0204]

Table 11

[0205]

Table 12

[0206] In addition to using a regimen of weekly induction dosing followed by maintenance dosing (every 4 weeks) (Q4W), the inventors will use a Q2W maintenance regimen to achieve higher exposure than is typically achieved with the treatment regimens typically used in the treatment of plaque psoriasis for the following reasons: : · For the population of patients with HS, a larger body weight (approximately 10 kg heavier for the HS population) is expected compared to the typical psoriasis population (Kimball et al( 2016) N Engl J Med;375(5):422-434), and thus, potentially higher doses are needed to achieve adequate exposure. Systemic exposure varies with body weight in an allometric relationship. For secukinumab clearance, the allometric exponent is estimated to be close to 1; in other words, doubling of body weight would result in approximately a two-fold increase in clearance and thus would decrease serum exposure (Bruin et al(2017) J Clin Pharmacol 57(7):876-885) . Thus, secukinumab dosing using higher exposure than obtained from psoriasis regimens The evaluation of the drug regimen is appropriate in the HS patient population. · For this disease with deep inflammatory skin lesions, a greater local skin exposure may be required than in psoriasis. · Clinical experience with adalimumab (HUMIRA®) in HS supports a dosing regimen that uses a greater exposure in HS than in psoriasis. · Importantly, as can be seen from Figure 4, the inventors have found that by using a shortened maintenance dosing interval (every 2 weeks) after the same induction period during the first month, it is possible to achieve a much higher and more consistent systemic exposure to secukinumab than can be achieved using a 4-week maintenance interval. This dosing discovery strategy is further supported by Figure 5, which shows a secukinumab trough concentration of greater than about 30 mcg / mL in psoriatic patients, where efficacy is maximized (PASI 90 - 60%). ​

Claims

1. A method for treating hidradenitis suppurativa (HS), comprising, during weeks 0, 1, 2, and 3, administering subcutaneously (SC) to a patient in need thereof an IL-17 antibody or an antigen-binding fragment thereof in a dose of about 300 mg to about 450 mg per week, and then a) starting in week 4, monthly (every 4 weeks); or b) starting in week 4, every other week (every 2 weeks) administering SC in a dose of about 300 mg to about 450 mg, wherein the IL-17 antibody or antigen-binding fragment thereof ii) comprises hypervariable regions described as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 of the immune i) An immunoglobulin V domain comprising the amino acid sequence described as SEQ ID NO: 8, and the sequence Ｈ ​ An immunoglobulin V domain containing the amino acid sequence described as number 10 Ｌ domain; iii) comprises hypervariable regions described as SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13 Immune globulin V Ｈ domain, and as described by SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 Immunoglobulin V domain containing a high-frequency variable region; or Ｌ or and Immunoglobulin V containing Ｈ domain, and as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 Immunoglobulin V domain containing the described high-frequency variable region Ｌ domain wherein the IL-17 antibody or antigen-binding fragment thereof binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains (the epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, P ro126, Ile127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain), and wherein the IL-17 antibody has a half-life of about 100 - 200 when measured by a biosensor system Method.

2. The method according to claim 1, wherein the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg or about 450 mg. K of pM Ｄ has, and the IL-17 antibody has an in vivo of about 23 to about 30 days

3. The method according to claim 1, comprising administering subcutaneously (SC) the IL-17 antibody or an antigen-binding fragment thereof in a dose of about 300 mg per week during weeks 0, 1, 2, and 3, and then starting in week 4, every other week (every 2 weeks), in a dose of about 300 mg.

4. The method according to claim 1, comprising administering subcutaneously (SC) the IL-17 antibody or an antigen-binding fragment thereof in a dose of about 300 mg per week during weeks 0, 1, 2, and 3, and then starting in week 4, monthly (every 4 weeks), in a dose of about 300 mg.

5. The patient has inflammatory lesion variables, Hidradenitis Suppurativa Clinical Response (HiSCR), Numerical Rating Scale (NRS), Modified Sartorius HS Score, Hidradenitis Suppurativa - Physician Global Assessment (HiS ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ (uppurativa-Physician Global Assessment)( HS-PGA)、 or the quality of life index of skin diseases (Dermatology Life Q uality Index) (DLQI), when measured by the persistence of the response after 1 year of treatment The method according to any one of claims 1 to 4, which achieves the persistence of the response.

6. The method according to any one of claims 1 to 5, which achieves the persistence of the response when the patient is measured by simple HiSCR (sHiSCR) after 1 year of treatment.

7. The method according to any one of claims 1 to 6, wherein the patient has been previously treated with a systemic drug for HS before treatment with the IL-17 antibody or antigen-binding fragment.

8. The method according to claim 7, wherein the systemic drug is selected from the group consisting of topical treatment, antibiotics, immunosuppressants, TNF-α inhibitors, IL- 1 antagonists, and combinations thereof.

9. The method according to any one of claims 1 to 8, wherein the patient has not been previously treated with a systemic drug or topical treatment for HS before treatment with the IL-17 antibody or antigen-binding fragment.

10. The method according to any one of claims 1 to 9, wherein the IL-17 antibody or antigen-binding fragment is administered in combination with at least one of TNF-α inhibitors, antibiotics, IL-1 inhibitors, or immunosuppressants.

11. The method according to any one of claims 1 to 10, wherein the dose of the IL-17 antibody or antigen-binding fragment is about 300 mg.

12. The method according to any one of claims 1 to 2 or 5 to 10, wherein the dose of the IL-17 antibody or antigen-binding fragment is about 450 mg.

13. The method according to any one of claims 1 to 12, wherein the patient has moderate to severe HS.

14. The method according to any one of claims 1 to 13, wherein the patient is an adult.

15. The method according to any one of claims 1 to 14, wherein the patient is a young person.

16. The method according to any one of claims 1 to 15, wherein the IL-17 antibody or antigen-binding fragment is dispensed in a pharmaceutical formulation, wherein the pharmaceutical formulation further comprises a buffer and a stabilizer.

17. The method according to any one of claims 1 to 16, wherein the pharmaceutical formulation is in liquid form.

18.

14. The method according to any one of claims 1 to 13, wherein the patient is an adult.

15. The method according to any one of claims 1 to 14, wherein the patient is a young person.

16. The IL-17 antibody or antigen-binding fragment is dispensed in a pharmaceutical formulation, where the pharmaceutical formulation further comprises a buffer and a stabilizer.

17. The method according to any one of claims 1 to 15, wherein the pharmaceutical formulation is in liquid form.

18. ​ ​ The method according to any one of claims 1 to 17, wherein the pharmaceutical preparation is in lyophilized form.

19. The method according to any one of claims 1 to 18, wherein the pharmaceutical preparation is dispensed within a prefilled syringe, vial, pen-type syringe, or autoinjector.

20. The dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical preparation is dispensed within a means for administration selected from the group consisting of a prefilled syringe, pen-type syringe, and autoinjector, and the means is dispensed within a kit, and the kit further comprises instructions for use. The method according to any one of claims 1 to 19.

21. The dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical preparation is dispensed within an autoinjector or prefilled syringe, and the autoinjector or prefilled syringe is dispensed within a kit, and the kit further comprises instructions for use. The method according to any one of claims 1 to 20.

22. The dose of the IL-17 antibody or antigen-binding fragment is about 300 mg, and the pharmaceutical preparation is dispensed within an autoinjector or prefilled syringe, and the autoinjector or prefilled syringe is dispensed within a kit, and the kit further comprises instructions for use. The method according to any one of claims 1 to 21.

23. The dose of the IL-17 antibody or antigen-binding fragment is about 450 mg, and the pharmaceutical preparation is dispensed within an autoinjector or prefilled syringe, and the autoinjector or prefilled syringe is dispensed within a kit, and the kit further comprises instructions for use. The method according to any one of claims 1 to 22.

24. The dose is 300 mg, which is administered as a single subcutaneous dose of a total volume of 2 ml from a formulation containing 150 mg / ml of the IL-17 antibody or antigen-binding fragment, wherein the pharmacological exposure of the patient to the IL-17 antibody or antigen-binding fragment is equal to the pharmacological exposure of the patient to the IL-17 antibody or antigen-binding fragment using two separate subcutaneous doses of a total volume of 1 ml each of the same formulation. The method according to any one of claims 1 to 23.

25. The dose is 300 mg, which is administered as two separate subcutaneous doses of a volume of 1 ml each from a formulation containing 150 mg / ml of the IL-17 antibody or antigen-binding fragment. The method according to any one of claims 1 to 23.

26. The IL-17 antibody or antigen-binding fragment thereof has a T of about 7 to 8 days ｍａｘ having, Claims 1 to The method according to any one of 25.

27. The method according to any one of claims 1 to 26, wherein the IL-17 antibody or antigen-binding fragment has an absolute bioavailability of about 60% to about 80%. The method according to any one of claims 1 to 26, wherein the IL-17 antibody or antigen-binding fragment has an absolute bioavailability of about 60% to about 80%.

28. The method according to any one of claims 1 to 27, wherein the IL-17 antibody or antigen-binding fragment is a human monoclonal antibody. The method according to any one of claims 1 to 27, wherein the IL-17 antibody or antigen-binding fragment is a human monoclonal antibody.

29. The IL-17 antibody or antigen-binding fragment thereof is IgG １ / κ isotype, please The method according to any one of claims 1 to 28.

30. The method according to any one of claims 1 to 29, wherein the patient has an HS-PGA score of ≧ 3 prior to treatment with the IL-17 antibody or antigen-binding fragment. The method according to any one of claims 1 to 29, wherein the patient has an HS-PGA score of ≧ 3 prior to treatment with the IL-17 antibody or antigen-binding fragment.

31. The method according to any one of claims 1 to 30, wherein the patient is classified as Hurley stage II or III prior to treatment with the IL-17 antibody or antigen-binding fragment. The method according to any one of claims 1 to 30, wherein the patient is classified as Hurley stage II or III prior to treatment with the IL-17 antibody or antigen-binding fragment.

32. The method according to any one of claims 1 to 31, wherein the patient achieves a simple HiSCR by week 16 of treatment. The method according to any one of claims 1 to 31, wherein the patient achieves a simple HiSCR by week 16 of treatment.

33. The method according to any one of claims 1 to 32, wherein the patient achieves an NRS30 by week 16 of treatment. The method according to any one of claims 1 to 32, wherein the patient achieves an NRS30 by week 16 of treatment.

34. The method according to any one of claims 1 to 33, wherein the patient has a reduction in HS erythema by week 16 of treatment. The method according to any one of claims 1 to 33, wherein the patient has a reduction in HS erythema by week 16 of treatment.

35. The method according to any one of claims 1 to 34, wherein the patient achieves a reduction of ≦ 6 as measured by DLQI by week 16 of treatment. The method according to any one of claims 1 to 34, wherein the patient achieves a reduction of ≦ 6 as measured by DLQI by week 16 of treatment.

36. When the method is used to treat a population of patients with moderate to severe HS, at least 51% of said patients achieve a simple HiSCR by week 16 of treatment in response to said administration step. When the method is used to treat a population of patients with moderate to severe HS, at least 51% of said patients achieve a simple HiSCR by week 16 of treatment in response to said administration step. The method according to any one of claims 1 to 35, wherein when the method is used to treat a population of patients with moderate to severe HS, at least 51% of said patients achieve a simple HiSCR by week 16 of treatment in response to said administration step.

37. When the method is used to treat a population of patients with moderate to severe HS, at least 40% of said patients achieve an NRS30 response by week 16 of treatment in response to said administration step. When the method is used to treat a population of patients with moderate to severe HS, at least 40% of said patients achieve an NRS30 response by week 16 of treatment in response to said administration step. The method according to any one of claims 1 to 36, wherein when the method is used to treat a population of patients with moderate to severe HS, at least 40% of said patients achieve an NRS30 response by week 16 of treatment in response to said administration step.

38. When the method is used to treat a population of patients with moderate to severe HS, less than 15% of said patients experience HS erythema during 16 weeks of treatment in response to said administration step. When the method is used to treat a population of patients with moderate to severe HS, less than 15% of said patients experience HS erythema during 16 weeks of treatment in response to said administration step. The method according to any one of claims 1 to 37, wherein when the method is used to treat a population of patients with moderate to severe HS, less than 15% of said patients experience HS erythema during 16 weeks of treatment in response to said administration step.

39. prior to treatment of the patient with the IL-17 antibody or antigen-binding fragment, as a result of HS having no extensive scarring (<20 fistulas), according to any one of claims 1 to 38 method.

40. the patient is further treated with at least 1 kind of topical drug therapy and at least 1 kind of disinfectant in combination with the IL-17 antibody or antigen-binding fragment thereof, according to any one of claims 1 to 39 method.

41. the patient is treated with the IL-17 antibody or antigen-binding fragment thereof for at least 1 year according to any one of claims 1 to 40 method.

42. the patient experiences rapid pain relief, measured by VAS or NRS, as early as 1 week after the first administration of the IL-17 antibody or antigen-binding fragment thereof, according to any one of claims 1 to 41 method.

43. the patient has a rapid decrease in CRP, measured using standard CRP measurement, as early as 1 week after the first administration of the IL-17 antibody or antigen-binding fragment thereof, according to any one of claims 1 to 4 2 method.

44. the patient has a decrease in the modified Sartorius score after 16 weeks of treatment according to any one of claims 1 to 43 method.

45. the patient has an improvement in DLQI after 16 weeks of treatment, according to any one of claims 1 to 44 method.

46. the IL-17 antibody or antigen-binding fragment is secukinumab, according to any one of claims 1 to 45

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