Biomarkers for diagnosing hidradenitis suppurativa

Abstract

This disclosure provides a diagnostic method, which can be used in combination with medical intervention, that uses one or more plasma biomarkers useful for identifying subjects with hidradenitis suppurativa (HS), measures the disease severity of HS, and measures the clinical response in subjects with HS. This disclosure relates to a method for testing for hidradenitis suppurativa (HS) in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein one or more plasma biomarkers are selected from the group consisting of IL8, IL36β, MDC, and TNFα.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority under § 119(e) of U.S. Patent Act to U.S. Provisional Patent Application No. 63 / 490,718 filed March 16, 2023, and the entire disclosure thereof is incorporated herein by reference. [Background technology]

[0002] Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease classified into three grades, Hurley stages I, II, and III, based on its severity. (Hurley H. Dermatologic surgery: principles and practice. 1996: 623-645). Hurley stage III is also known as severe hidradenitis suppurativa.

[0003] Hidradenitis suppurativa (HS), also known as reverse acne, is a chronic inflammatory skin disease characterized by inflammatory nodules, abscesses, sinus formation and fistula formation, as well as skin scarring. It is most common in areas with a high concentration of apocrine glands, such as the armpits, submammary glands, groin, perineum, and perianal area. In its moderate and severe forms, HS is debilitating and causes significant discomfort, pain, anxiety and depression, and a reduced quality of life.

[0004] The exact cause of HS has not been identified, but genetic defects in the gamma-secretase-coding gene have been explained in subjects with HS. Possible target proteins include Notch, E-cadherin, and nicastriin. Notch plays a crucial role in hair follicle development, and defects in Notch may lead to epidermal cyst formation, dysregulation of normal T cell-mediated immune responses, and suppression of Toll-like receptor 4-induced pro-inflammatory macrophage-mediated cytokine responses (Radtke et al, 2010; Wang et al, 2010). Smoking and obesity are associated with HS (Prens and Deckers, 2015), as are hyperhidrosis, androgen dysfunction, or possibly genetic factors. Some reports suggest that HS is at least partially a neutrophil-mediated disorder.

[0005] Treatment options for patients with HS include topical and systemic antibiotics, analgesics, and anti-TNF-α agents such as adalimumab. Other drugs such as cyclosporine A, dapsone, and isotretinoin have been used, but with limited outcomes (Napolitano et al, 2017). Despite the available treatment options, the majority of patients respond only partially and / or temporarily.

[0006] Another possible treatment option disclosed in U.S. Patent Application Publication No. 2018 / 0280530 and U.S. Patent Application Publication No. 2018 / 028425 is the use of C5a-targeted antibodies to treat patients suffering from HS.

[0007] Further advances in potential treatment options for subjects with severe hidradenitis suppurativa, also known as Hurley stage III, are disclosed in U.S. Patent Application Publication 2022 / 125775, which describes certain C5aR inhibitors, such as avacopan, that are particularly effective in treating subjects with Hurley stage III requiring such treatment. Such targeted therapies for subjects with Hurley stage III have also demonstrated the need for new and improved methods to identify subjects with Hurley stage III who could benefit from such targeted therapies.

[0008] The treatment options and diagnostic methods available to patients with HS, including Hurley stage III, are limited. Therefore, there is an urgent need for new and improved methods to identify patients with HS and Hurley stage III who could benefit from effective therapies for these patients. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] U.S. Patent Application Publication No. 2018 / 0280530 [Patent Document 2] U.S. Patent Application Publication No. 2018 / 028425 [Patent Document 3] U.S. Patent Application Publication No. 2022 / 125775 [Non-patent literature]

[0010] [Non-Patent Document 1] Hurley H.Dermatologic surgery: principles and practice.1996:623-645 [Non-Patent Document 2] Radtke et al, 2010 [Non-Patent Document 3] Wang et al, 2010 [Non-Patent Document 4] Prens and Deckers, 2015 [Non-Patent Document 5] Napolitano et al, 2017 [Overview of the Initiative] [Means for solving the problem]

[0011] This disclosure provides a variety of novel diagnostic methods for subjects having hidradenitis suppurativa (HS). In one embodiment, the disclosure relates to a method for testing for hidradenitis suppurativa (HS) in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of IL8, IL36β, MDC, and TNFα.

[0012] In another embodiment, the present disclosure relates to a method for treating a subject having hidradenitis suppurativa (HS), comprising: testing for HS in the subject, which includes measuring one or more plasma biomarkers in a sample taken from the subject, the one or more plasma biomarkers being selected from the group consisting of IL8, IL36β, MDC and TNFα; and treating the subject by administering one or more drugs in a therapeutically effective amount for the treatment of HS.

[0013] In another embodiment, the present disclosure relates to a method for measuring the disease severity of HS in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of APRIL, BAFF, C5b-9, CD25, IL6, IL8, and S100A8 / 89.

[0014] In another embodiment, the present disclosure is a method of treating a subject having Hurley stage III, comprising measuring the disease severity of HS in the subject, including measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of APRIL, BAFF, C5b-9, CD25, IL6, IL8, and S100A8 / 89; and treating the subject by administering a therapeutically effective amount of one or more agents for the treatment of Hurley stage III.

[0015] In another embodiment, the present disclosure is a method of measuring the HS clinical response (HiSCR) rate in a subject having HS being treated with an agent effective to treat HS, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of CD25, complement factor B, IL8, NGAL, S100A8 / A9, and VEGF.

[0016] Other objects, features, and advantages of the present invention will become apparent to those skilled in the art from the following detailed description and drawings.

Brief Description of the Drawings

[0017] [Figure 1] Shows a schematic diagram of a Phase II trial design.

Modes for Carrying Out the Invention

[0018] I. Overview The present disclosure relates to a method of identifying a subject having HS, a method of identifying a subject having Hurley stage III, a method of treating a subject having HS or Hurley stage III, a companion diagnosis for a subject having HS or Hurley stage III, and a method of measuring the HS clinical response in a subject having Hurley stage III.

[0019] The Hurley staging system was developed to classify HS patients by disease severity, with Hurley stage III indicating severe disease. Plasma biomarkers for clinical response and disease severity were identified from subjects with HS in the Phase II AURORA trial. A group of biomarkers that can predict the presence of HS in subjects was identified. A second group of biomarkers that can distinguish between Hurley stage III and less severe forms of HS was identified. A third set of biomarkers that can measure the high clinical response rate (HiSCR) of HS in subjects with HS was identified.

[0020] II. Definitions and Abbreviations As used herein, the terms “to treat” or “treatment” encompass both disease-modifying treatments and symptomatic treatments, both of which may be prophylactic (i.e., before the onset of symptoms, to prevent, delay, or reduce the severity of symptoms) or treatment (i.e., after the onset of symptoms, to reduce the severity and / or duration of symptoms). Treatment methods provided herein generally involve administering to a patient one or more effective amounts of the compounds provided herein. Suitable patients include those suffering from or susceptible to the disorders or diseases identified herein (i.e., prophylactic treatment). Patients typical of the treatments described herein include mammals, particularly primates, and especially humans. Other suitable patients include domesticated companion animals such as dogs, cats, and horses, or livestock such as cattle, pigs, and sheep.

[0021] The terms “significant increase,” “significant rise,” “significant decrease,” and “significant decrease” mean that the volume of the sample changes by 5%, 10%, 15%, 20%, or more between the test sample and the reference sample.

[0022] The term "pharmaceutically acceptable salt" includes salts of active compounds prepared with relatively non-toxic acids or bases, depending on the specific substituents found in the compounds described herein. If the compounds of this disclosure contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compound with a sufficient amount of the desired base, either without a solvent or in a suitable inert solvent. Examples of pharmaceutically acceptable salts derived from inorganic bases include aluminum salts, ammonium salts, calcium salts, copper salts, ferric salts, ferrous salts, lithium salts, magnesium salts, manganese salts, manganese salts, potassium salts, sodium salts, and zinc salts. Pharmaceutically acceptable salts derived from organic bases include salts of primary, secondary, and tertiary amines, including substituted amines, cyclic amines, and natural amines. Examples include arginine salt, betaine salt, caffeine salt, choline salt, N,N'-dibenzylethylenediamine salt, diethylamine salt, 2-diethylaminoethanol salt, 2-dimethylaminoethanol salt, ethanolamine salt, ethylenediamine salt, N-ethylmorpholine salt, N-ethylpiperidine salt, glucamine salt, glucosamine salt, histidine salt, hydravamin salt, isopropylamine salt, lysine salt, methylglucamine salt, morpholine salt, piperazine salt, piperadine salt, polyamine resin salt, procaine salt, purine salt, theobromine salt, triethylamine salt, trimethylamine salt, tripropylamine salt, and tromethamine salt. If the compounds of this disclosure contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either without a solvent or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogen bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, monohydrogen sulfate, hydroiodic acid, or phosphorous acid, and salts derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, and methanesulfonic acid.This also includes salts of amino acids such as alginates and salts of organic acids such as glucuronic acid or galactunoric acid (see, for example, Berge, SM, et al, “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain compounds of this disclosure contain both basic and acidic functional groups that allow the compound to be converted into either a base-addition salt or an acid-addition salt.

[0023] The neutral form of the compound can be regenerated in the conventional manner by contacting the salt with a base or acid and isolating the parent compound. This parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise, this salt is equivalent to the parent form of the compound for the purposes of this disclosure.

[0024] In addition to salt forms, certain compounds of formula I exist in prodrug forms. Prodrugs of the compounds described herein are compounds that readily undergo chemical transformation under physiological conditions to provide the compounds of the disclosure. In addition, prodrugs can be converted to the compounds of the disclosure by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the disclosure when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.

[0025] Certain compounds of formula I can exist in solvated forms, including non-solvated and hydrated forms. Generally, the solvated forms are equivalent to the non-solvated forms and are intended to be included within the scope of this disclosure. Certain compounds of this disclosure can exist in a wide variety of crystalline or amorphous forms. Generally, all physical forms are equivalent with respect to the uses envisioned by this disclosure and are intended to be within the scope of this disclosure.

[0026] Certain compounds of formula I have an asymmetric carbon atom (optical center) or a double bond, and racemates, diastereomers, geometric isomers, positional isomers, and individual isomers (e.g., separated enantiomers) are all intended to be included within the scope of the present invention. Tautomers of the compounds of this disclosure are also intended to be included within the scope of this disclosure. The compounds of this disclosure may also contain atomic isotopes in unnatural ratios in one or more atoms constituting such compounds. For example, a compound may contain tritium ( 3 H), Iodine-125( 125 I) or carbon-14 ( 14 They can be radiolabeled with radioactive isotopes such as C). All isotopic variations of the compounds of this disclosure, whether radioactive or not, are intended to be included within the scope of this disclosure.

[0027] When used herein, the wavy line intersects a single, double, or triple bond in any chemical structure shown herein. [ka] The symbol represents an additional bond point where a single, double, or triple bond attaches to the rest of the molecule.

[0028] [Table A]

[0029] III. Detailed Description of Embodiments Embodiment 1 of the present disclosure relates to a method for testing for hidradenitis suppurativa (HS) in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of IL8, IL36β, MDC, and TNFα.

[0030] Embodiment 2a of this disclosure is a method for testing HS in an object described in Embodiment 1, the method comprising measuring three or more of the aforementioned plasma biomarkers.

[0031] Embodiment 2b of this disclosure is a method for testing HS in an object described in Embodiment 1, the method comprising measuring IL8, IL36β, MDC and TNFα.

[0032] Embodiment 3 of this disclosure relates to a method for testing HS in an object described in any one of Embodiments 1 to 2, wherein the plasma biomarker is measured directly in plasma using liquid-phase multianalyte profiling technology.

[0033] Embodiment 4 of the present disclosure is a method for testing HS in a subject described in any one of Embodiments 1 to 3 or any sub-embodiment thereof, wherein one or more plasma biomarkers measured in the subject are compared to a corresponding reference value; and the presence of HS is determined according to one or more plasma biomarkers whose value is significantly increased or decreased from a corresponding reference value.

[0034] Embodiment 5 of this disclosure relates to a method for testing HS in a subject described in Embodiment 4, wherein one or more plasma biomarkers include IL-8, and the amount of IL-8 in the subject is higher than the corresponding reference value.

[0035] Embodiment 6 of this disclosure is a method for testing HS in a subject described in any one of Embodiments 4 or 5, wherein one or more plasma biomarkers include TNFα, and the amount of TNFα in the subject is higher than the corresponding reference value.

[0036] Embodiment 7 of this disclosure relates to a method for testing HS in a subject described in any one of Embodiments 4 to 6, wherein one or more plasma biomarkers include IL36β, and the amount of IL36β in the subject is lower than the corresponding reference value.

[0037] Embodiment 8 of the present disclosure relates to a method for testing HS in a subject described in any one of Embodiments 4 to 7, wherein one or more plasma biomarkers include MDC, and the amount of MDC in the subject is lower than the corresponding reference value.

[0038] Embodiment 9 of this disclosure relates to a method for testing HS in an object described in any one of Embodiments 4 to 8, wherein the corresponding reference value for one or more plasma biomarkers is the amount of the corresponding plasma biomarker in a healthy object.

[0039] Embodiment 10 of the present disclosure is a method for treating an object having HS; Examining the HS in the subject according to the method described in any one of the embodiments 1 to 9 or any of the lower embodiments thereof; and The present invention relates to a method of treating a subject by administering one or more therapeutically effective doses of a drug for the treatment of HS.

[0040] Embodiment 11 of this disclosure relates to Embodiment 10 in which the results of the inspection are an indicator for the treatment of HS.

[0041] Embodiment 12 of this disclosure relates to an embodiment in which TNFα is approximately 1 to 3 times higher in subjects having HS; IL36β is approximately 25% to 75% lower in subjects having HS; IL8 is approximately 2 to 4 times higher in subjects having HS; and MDC is approximately 10% to 50% lower in subjects having HS.

[0042] Embodiment 13 of the present disclosure relates to any one of Embodiments 10 to 12, wherein the examination of HS in the subject is a companion diagnostic examination prior to treatment of the subject, and the results of the examination are indicators for treatment of HS.

[0043] Embodiment 13a of the present disclosure relates to any one of embodiments 10 to 13 in which a plasma biomarker is measured by a magnetic bead-based Luminex assay.

[0044] Embodiment 14 of the present disclosure relates to any one of Embodiments 10 to 13 or any of its sub-embodiments, wherein one or more agents are selected from the group consisting of C5aR inhibitors, C5a inhibitors, adalimumab, antibiotics, retinoids, spironolactone or finasteride and metformin.

[0045] Non-exclusive examples of C5aR inhibitors include avacopan and INF904. Non-exclusive examples of C5a inhibitors include biroberimab and IFX002.

[0046] Embodiment 15 of this disclosure is a drug that is a C5aR inhibitor of formula I: [ka] or a pharmaceutically acceptable salt thereof, In the formula, each R 1 These are independently selected from the group consisting of CH3, CF3, CH2CH3, Cl, 1-pyrrolidine, -O-CH(CH3)2, and CH2OH; Each R 2 It was independently selected from the group consisting of CH3 and F; Embodiment 14 relates to a therapeutically effective dose of Formula I administered twice daily, ranging from 15 mg to approximately 60 mg.

[0047] Embodiment 15a of this disclosure describes a compound in which [ka] Embodiment 15 relates to a pharmaceutically acceptable salt thereof.

[0048] Embodiment 16 of this disclosure is a compound of the formula [ka] Embodiment 15 relates to abacopan or a pharmaceutically acceptable salt thereof having [a specific compound].

[0049] Embodiment 17 of this disclosure relates to Embodiment 16 in which the therapeutically effective dose of the compound to be administered is approximately 30 mg twice daily.

[0050] Embodiment 17a of this disclosure relates to Embodiment 16 in which the subject receives treatment for at least 12 weeks.

[0051] Embodiment 18 of the present disclosure relates to a method for measuring the disease severity of HS in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of APRIL, BAFF, C5b-9, CD25, IL6, IL8, and S100A8 / 89.

[0052] Embodiment 19 of this disclosure is a method for measuring the disease severity of HS in a subject described in Embodiment 18, the method comprising measuring two or more of the aforementioned plasma biomarkers.

[0053] Embodiment 20 of this disclosure is a method for measuring the disease severity of HS in a subject described in Embodiment 19, the method comprising measuring three or more of the aforementioned plasma biomarkers.

[0054] Embodiment 20a of the present disclosure is a method for measuring the disease severity of HS in a subject described in Embodiment 20, the method comprising measuring four or more of the aforementioned plasma biomarkers.

[0055] Embodiment 20b of the present disclosure is a method for measuring the disease severity of HS in a subject described in Embodiment 20, the method comprising measuring five or more of the aforementioned plasma biomarkers.

[0056] Embodiment 20c of the present disclosure is a method for measuring the disease severity of HS in a subject described in Embodiment 20, the method comprising measuring six or more of the aforementioned plasma biomarkers.

[0057] Embodiment 20d of the present disclosure is a method for measuring the disease severity of HS in the subject described in Embodiment 20, the method comprising measuring APRIL, BAFF, C5b-9, CD25, IL6, IL8 and S100A8 / 89.

[0058] Embodiment 21 of the present disclosure is a method for measuring the disease severity of HS in a subject described in any one of embodiments 18-20 or any sub-embodiment thereof, wherein one or more plasma biomarkers measured in the subject are compared to a corresponding reference value; and the disease severity of HS is determined according to one or more plasma biomarkers whose value is significantly increased or decreased from a corresponding reference value.

[0059] Embodiment 22 of this disclosure relates to a method for measuring the disease severity of HS in subjects described in Embodiment 21, wherein one or more plasma biomarkers include APRIL, and a lower amount of APRIL in a subject than the corresponding reference value indicates a more severe HS.

[0060] Embodiment 23 of the present disclosure is a method for measuring the disease severity of HS in subjects described in Embodiment 21 or 22, wherein one or more plasma biomarkers include BAFF, and a BAFF level lower than the corresponding reference value in a subject indicates a more severe HS.

[0061] Embodiment 24 of the present disclosure is a method for measuring the disease severity of HS in subjects described in any one of Embodiments 21 to 23, wherein one or more plasma biomarkers include C5b-9, and a lower amount of C5b-9 in a subject than the corresponding reference value indicates a more severe HS.

[0062] Embodiment 25 of the present disclosure is a method for measuring the disease severity of HS in a subject described in any one of Embodiments 21 to 24, wherein one or more plasma biomarkers include CD25, and a CD25 level lower than the corresponding reference value in the subject indicates a more severe HS.

[0063] Embodiment 27 of the present disclosure is a method for measuring the disease severity of HS in a subject described in any one of Embodiments 21 to 25, wherein one or more plasma biomarkers include IL-6, and a higher amount of IL-6 in the subject than the corresponding reference value indicates a more severe HS.

[0064] Embodiment 28 of the present disclosure is a method for measuring the disease severity of HS in a subject described in any one of Embodiments 21 to 26, wherein one or more plasma biomarkers include IL-8, and a higher amount of IL-8 in the subject than the corresponding reference value indicates a more severe HS.

[0065] Embodiment 28 of the present disclosure is a method for measuring the disease severity of HS in a subject described in any one of Embodiments 21 to 27, wherein one or more plasma biomarkers include S100A8 / 89, and a higher amount of S100A8 / 89 in a subject than the corresponding reference value indicates a more severe HS.

[0066] Embodiment 29 of this disclosure relates to a method for measuring the disease severity of HS in subjects described in any one of embodiments 20 to 27 or any sub-embodiments thereof, wherein the corresponding reference value for one or more plasma biomarkers is the amount of the corresponding plasma biomarker in a healthy subject.

[0067] Embodiment 30 of this disclosure is a method for treating a subject having Hurley disease stage III: Measuring the disease severity of HS according to the method described in any one of the embodiments 18 to 29 or any of its sub-embodiments; and The present invention relates to a method of treating a subject by administering one or more therapeutically effective doses of a drug for the treatment of Hurley disease stage III.

[0068] Embodiment 31 of this disclosure relates to a method for treating a subject having Hurley disease stage III as described in Embodiment 30, wherein the results of measuring the disease severity of HS are an indicator for the treatment of Hurley disease stage III.

[0069] Embodiment 32 of the present disclosure relates to the method of any one embodiment of Embodiment 30 or 31, wherein the measurement of disease severity of HS is a companion diagnostic test performed before treatment of the subject, and the test results are an indicator for treatment of Hurley stage III.

[0070] Embodiment 33 of this disclosure relates to a method for treating a subject having Hurley disease stage III as described in any one of embodiments 30 to 32, wherein the plasma biomarker is measured by a multianalyte assay.

[0071] Embodiment 34 of the present disclosure relates to a method for treating a subject having Hurley stage III as described in any one of embodiments 30 to 33, wherein a plasma biomarker measurement is compared to a corresponding reference value; and the severity of HS is determined according to the Hurley clinical staging system as determined by a physician.

[0072] Embodiment 35 of the present disclosure relates to a method for treating a subject having Hurley disease stage III as described in any one of Embodiments 30 to 34, wherein the agent is selected from the group consisting of C5aR inhibitors, C5a inhibitors, adalimumab, antibiotics, retinoids, spironolactone or finasteride and metformin.

[0073] Non-exclusive examples of C5aR inhibitors include avacopan and INF904. Non-exclusive examples of C5a inhibitors include biroberimab and IFX002.

[0074] Embodiment 36 of this disclosure is a method for treating a subject having Hurley disease stage III as described in Embodiment 35, wherein the agent is a C5aR inhibitor of formula I: [ka] or a pharmaceutically acceptable salt thereof, In the formula, each R 1 These are independently selected from the group consisting of CH3, CF3, CH2CH3, Cl, 1-pyrrolidine, -O-CH(CH3)2, and CH2OH; Each R 2 It was independently selected from the group consisting of CH3 and F; The therapeutically effective dose of Formula I administered is 15 mg to approximately 60 mg twice daily.

[0075] Embodiment 36a of the present disclosure is a method for treating a subject having Hurley disease stage III as described in Embodiment 36, wherein the compound is [ka] or the method of providing a pharmaceutically acceptable salt thereof.

[0076] Embodiment 37 of the present disclosure is a method for treating a subject having Hurley disease stage III as described in Embodiment 36, wherein the compound is of the formula [ka] The present invention relates to a method for having abacopan or a pharmaceutically acceptable salt thereof.

[0077] Embodiment 38 of this disclosure relates to a method for treating a subject having Hurley disease stage III as described in Embodiment 37, wherein the therapeutically effective dose of the compound administered is approximately 30 mg twice daily.

[0078] Embodiment 38a of this disclosure relates to a method for treating a subject having Hurley disease stage III as described in Embodiment 38, wherein the subject receives treatment for at least 12 weeks.

[0079] Embodiment 39 of the present disclosure relates to a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective in treating HS, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of CD25, complement factor B, IL8, NGAL, S100A8 / A9, and VEGF.

[0080] Embodiment 40 of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 39, the method comprising measuring two or more of the aforementioned plasma biomarkers.

[0081] Embodiment 41 of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 39, the method comprising measuring three or more of the aforementioned plasma biomarkers.

[0082] Embodiment 41a of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 39, the method comprising measuring four or more of the aforementioned plasma biomarkers.

[0083] Embodiment 41b of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 39, the method comprising measuring five or more of the aforementioned plasma biomarkers.

[0084] Embodiment 41c of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 39, the method comprising measuring CD25, complement factor B, IL8, NGAL, S100A8 / A9 and VEGF.

[0085] Embodiment 42 of the present disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in any one of Embodiments 39 to 41, wherein the plasma biomarker is measured by a multianalyte assay.

[0086] Embodiment 43 of the present disclosure is a method for measuring the high-level clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS as described in any one of Embodiments 39 to 42, wherein the biomarker is a method used to guide a biomarker test that can be performed on an HS patient to indicate drug treatment.

[0087] Embodiment 44 of the present disclosure relates to a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective in treating HS as described in any one of Embodiments 39 to 43, wherein the drug is selected from the group consisting of C5aR inhibitors, C5a inhibitors, adalimumab, antibiotics, retinoids, spironolactone or finasteride and metformin.

[0088] Embodiment 45 of this disclosure is a method for measuring the high-level clinical response (HiSCR) rate of HS in a subject having HS treated with a drug effective for treating HS as described in Embodiment 44, wherein the drug is a C5aR inhibitor of formula I: [ka] or a pharmaceutically acceptable salt thereof, In the formula, each R 1is independently selected from the group consisting of CH3, CF3, CH2CH3, Cl, 1-pyrrolidine, -O-CH(CH3)2 and CH2OH; each R 2 is independently selected from the group consisting of CH3 and F; Relates to a method in which a therapeutically effective amount of formula I is administered twice a day, at 15 mg to about 60 mg.

[0089] Embodiment 45a of the present disclosure is a method for measuring the HS clinical response (HiSCR) rate in a subject having HS treated with an agent effective to treat HS as described in Embodiment 45, wherein the compound is [Chemical formula] or a pharmaceutically acceptable salt thereof.

[0090] Embodiment 46 of the present disclosure is a method for measuring the HS clinical response (HiSCR) rate in a subject having HS treated with an agent effective to treat HS as described in Embodiment 45, wherein the compound is of the formula [Chemical formula] Relates to a method which is avacopan having or a pharmaceutically acceptable salt thereof.

[0091] Embodiment 47 of the present disclosure is a method for measuring the HS clinical response (HiSCR) rate in a subject having HS treated with an agent effective to treat HS as described in Embodiment 46, wherein the therapeutically effective amount of the compound administered is about 30 mg twice a day.

[0092] Embodiment 47a of the present disclosure is a method for measuring the HS clinical response (HiSCR) rate in a subject having HS treated with an agent effective to treat HS as described in Embodiment 47, wherein the subject is treated for at least 12 weeks.

[0093] Embodiment 48 of this disclosure relates to a method for treating a subject having Hurley disease stage III as described in Embodiment 35, wherein the drug is selected from the group consisting of INF904, virobelimab, and IFX002.

[0094] Embodiment 49 of this disclosure relates to a method for measuring the high-level clinical response (HiSCR) rate of HS in subjects having HS treated with a drug effective for treating HS as described in Embodiment 44, wherein the drug is selected from the group consisting of INF904, virobelimab, and IFX002. [Examples]

[0095] IV. Examples The following embodiments are provided for illustrative purposes only and are not limiting to the present disclosure.

[0096] Example 1 - Phase 2 Clinical Trial (ClinicalTrials.gov Identifier: NCT03852472) The study was a randomized, double-blind, placebo-controlled, three-arm phase 2 trial involving 435 patients with moderate to severe hidradenitis suppurativa (Hurley stage II or III). Participants were randomized in a 1:1:1 ratio to receive either 10 mg of avacopan twice daily, 30 mg of avacopan twice daily, or placebo twice daily for 12 weeks. Following the 12-week double-blind treatment period, the placebo group was re-randomized in a 1:1 ratio to receive either 10 mg or 30 mg of avacopan twice daily for a further 24 weeks. Those treated with avacopan continued to receive the same dose (10 mg or 30 mg twice daily) for another 24 weeks.

[0097] Participants received the study treatment for 36 weeks and were followed up for 8 weeks to evaluate safety and efficacy. The primary efficacy analysis was performed at 12 weeks.

[0098] The primary efficacy endpoint was assessed by the proportion of patients achieving a clinically significant clinical response (HiSCR) to hidradenitis suppurativa at week 12.

[0099] standard Selection criteria: 18 years of age or older • Clinical diagnosis of HS (Hurley disease stage II or III) confirmed by a dermatologist at least 6 months prior to screening. • HS lesions are located in at least two distinct anatomical sites. • Insufficient response or loss of response to systemic antibiotic administration for 90 days or more. • At the time of screening, the patient must have at least five inflammatory nodules or abscesses. • Use appropriate contraception for individuals of reproductive capacity and their partners. • They have the intention and ability to submit written consent.

[0100] Exclusion criteria: • Pregnant or breastfeeding Other skin conditions that may interfere with the assessment of HS • Rapid progression within 30 days prior to screening and expansion of HS • More than 20 drainage fistulas at the time of screening. • Any anti-TNF-α treatment for HS or other conditions prior to the first day of hospital visit is prohibited. Exception: Patients who have previously been treated with anti-TNF-α drugs and have discontinued treatment for >12 weeks prior to the first day of hospital visit are permitted to register. Systemic antibiotics are generally excluded. • Use of topical antibiotics within 14 days prior to day 1 is excluded. • Started topical prescription medication for HS within 14 days prior to screening. • Systemic drugs for HS, including biological agents and other systemic therapies • For any reason, the patient has received or is expected to need oral or transdermal opioid analgesics (excluding tramadol) within 14 days prior to their first visit to the clinic.

[0101] The results of NCT03852472 showed that avacopan demonstrated a statistically significant dose-dependent improvement in HiSCR (Hydradenitis Suppurativa Clinical Response) compared to placebo at 12 weeks in pre-selected patients with stage III Hurley disease (severe HS). At 12 weeks, there was a consistent decrease not only in the number of ANs (abscesses and inflammatory nodules), drainage fistulas, and abscesses, but also in the International HS Severity Score (IHS4) in patients with stage III Hurley disease. Avacopan was demonstrated to be safe and well-tolerated in HS patients.

[0102] Surprisingly, although not in the Hurley stage II subgroup, in the Hurley stage III subgroup, the rate of reduction from baseline was generally numerically greater in the avacopan 30 mg BID group compared to the placebo group or the avacopan 10 mg BID group.

[0103] The proportion of subjects achieving HiSCR at week 12 is calculated by dividing the number of subjects in each treatment group who showed at least a 50% decrease in the number of abscesses and inflammatory nodules (ANs) from baseline at week 12, with no increase in the number of abscesses and no increase in the drainage fistula count by the total number of subjects with no missing data. The p-value is obtained from the Cochran-Mantel-Haenszel (CMH) test stratified by the stratification factors of Hurley stage (Hurley stage II vs. III) and use of anti-TNF drugs (untreated vs. previously treated).

[0104] As shown in Table 1, neither avacopan group (10 mg BID or 30 mg BID) performed better than the placebo group in terms of HiSCR at week 12 in the Hurley stage II subgroup (Table 1). The avacopan 10 mg BID group (21.4%) was statistically inferior to the placebo group (35.3%, p=0.0473).

[0105] [Table 1]

[0106] At week 12, the HiSCR in the Hurley stage III subgroup was significantly higher in the avacopan 30 mg BID group (42.6%) compared to the placebo group (22.2%; p=0.0349). There was no significant difference between the avacopan 10 mg BID group (24.0%) and the placebo group (22.2%) (Table 2).

[0107] [Table 2]

[0108] The confirmed clinical efficacy of avacopan 30 mg BID based on HiSCR at week 12 in the Hurley stage III subgroup is also supported by observations during period 1, where the percentage reduction from baseline to week 1 in AN count, DF count, and IHS4 score was consistently numerically greater in the avacopan 30 mg BID group compared to the placebo group or the avacopan 10 mg BID group, not in the Hurley stage II subgroup.

[0109] The reduction rates in the Hurley stage III subgroup in the avacopan 30 mg BID group and the placebo group were as follows: • In the Avacopan 30mg BID group (40.8%), the rate of decrease in AN count at week 12 was numerically greater compared to the placebo group (23.7%). • In the Avacopan 30mg BID group (45.2%), the rate of decrease in DF count at week 12 was numerically greater compared to the placebo group (24.0%). • In the Avacopan 30mg BID group (36.9%), the rate of decline in IHS4 score at week 12 was numerically greater compared to the placebo group (20.7%).

[0110] Example 2 - Plasma biomarkers for clinical response and disease severity identified from patients with hidradenitis suppurativa in the Phase II AURORA trial. Plasma samples were collected at baseline before the start of treatment from 68 HS patients enrolled in the Phase II AURORA trial (NCT03852472) and from 20 unrelated, age- and sex-matched healthy controls.

[0111] [Table 3]

[0112] The levels of 31 plasma biomarkers listed in Table 4, including the following, were evaluated: • Plasma complement factors Chemokines • Cytokine

[0113] [Table 4]

[0114] The primary objective of this study was to identify baseline biomarkers to predict or enhance clinical response to abacopan in patients (N=68). This study included comparing the following groups: - Compare baseline samples from responders and non-responders for each treatment group. -Comparison of Avacopan 30mg versus placebo group at week 12

[0115] A secondary objective was to identify biomarkers for differentiating between Hurley disease stages II and III, and between HS and HC, by making the following comparisons: - Compare plasma from normal donors (N=20) with baseline plasma samples from HS patients (N=68). - Compare baseline plasma samples between patients with Hurley disease stage II and Hurley disease stage III.

[0116] Logistic regression was used to model clinical response (HiSCR responders vs. non-responders) and Hurley stage (II vs. III) using naturally log-transformed baseline biomarker values ​​and treatment (Avacopan vs. placebo) as explanatory variables. A stepwise procedure was used to identify biomarker explanatory variables. In stepwise selection, we attempted to remove non-significant biomarkers from the model before adding significant biomarkers to the model. Before the first step, we fitted a model with only intercepts and determined individual score statistics for potential variables. A significance level of 0.2 was required to include a variable in the model, and a significance level of 0.25 was required for a variable to remain in the model. Due to the small size of the dataset, a selection criterion of p<0.20 was considered here to not exclude potentially important biomarkers.

[0117] Based on the analysis of these 31 plasma biomarkers, we created the following three final models for groups of plasma biomarkers that have predictive value based on statistically significant values ​​(p-value <= 0.05).

[0118] [Table 5]

[0119] The plasma biomarkers IL8, IL36β, MDC, and TNFα in Table 6 were measured using a plasma-compatible multianalyte technique (e.g., Luminex xMAP). Liquid-phase multianalyte profiling techniques are based on the principle of sandwich ELISA and quantified by fluorescence readings converted to pg / ml units using a standard curve. IL8 and TNFα were measured using the Luminex Performance Human High Sensitivity Cytokine Magnetic Panel A (FCSTM09), IL36β was measured using the Luminex Performance Human High Sensitivity Cytokine Magnetic Panel B (FCSTM14), and MDC was measured using the Luminex Human Discovery Assay (LXSAHM) from R&D Systems. Luminex-based assays were performed according to the manufacturer's protocol and read using a Luminex 100 analyzer.

[0120] [Table 6]

[0121] CD25 / IL-2Ra was measured by the Quantikine® ELISA assay (DR2A00), and S100A8 / A9 was measured by the Quantikine® ELISA assay (DS8900) from R&D Systems. C5b-9 was measured by the QUIDEL MicroVue C5b-9 EIA (A020). ELISA-based assays were performed according to the manufacturer's protocol and read using a flex station 3. APRIL and BAFF were measured by the Luminex Human Discovery Assay (LXSAHM). IL6 was measured by the Luminex performance human high sensitivity cytokine magnetic panel B (FCSTM14), and IL8 was measured by the Luminex performance human high sensitivity cytokine magnetic panel A (FCSTM09) from R&D Systems. Luminex-based assays were performed according to the manufacturer's protocol and read using a Luminex 100 analyzer.

[0122] [Table 7]

[0123] CD25 / IL-2Ra was measured by the Quantikine® ELISA assay (DR2A00), and S100A8 / A9 was measured by the Quantikine® ELISA assay (DS8900) from R&D Systems. ELISA-based assays were performed according to the manufacturer's protocol and read using a flex station 3. Complement factor B was measured by the MILLIPLEX® MAP human complement magnetic bead panel 2 (HCMP2MAG-19K) Luminex assay from EMD Millipore. IL8 was measured by the Luminex performance human high sensitivity cytokine magnetic panel A (FCSTM09) from R&D Systems. VEGF was measured by the Luminex performance human high sensitivity cytokine magnetic panel A (FCSTM09). NGAL was measured by the Luminex human discovery assay (LXSAHM) from R&D Systems. Luminex-based assays were performed according to the manufacturer's protocol and read using a Luminex 100 analyzer.

[0124] The interpretations for Tables 5-7 are derived from logistic regression analysis.

[0125] A p-value <= 0.05 indicates that the biomarker is statistically significant in predicting outcomes (HiSCR, HS disease (HS patients vs. healthy subjects), and HS Hurley stage (II vs. III)).

[0126] The "Estimated Effect" (β) measures how much a biomarker can influence the prediction of an outcome. For example, in Table 7, increasing the CD25 / IL2Ra level by 0.1 units (on a logarithmic scale) would increase the odds of achieving HiSCR by 2.11 times.

[0127] Increasing complement factor B levels by 0.1 units (on a logarithmic scale) would reduce the odds of achieving HiSCR to 0.61 (a 39% decrease in odds).

[0128] While the above disclosure has been illustrated and illustrated in some detail for the purpose of clarifying understanding, those skilled in the art will understand that certain modifications and variations may be made within the scope of the appended claims. In the event of any conflict between this application and the references provided herein, this application shall prevail.

Claims

1. A method for testing for hidradenitis suppurativa (HS) in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of IL8, IL36β, MDC, and TNFα.

2. A method for testing HS in a subject according to claim 1, comprising measuring two or more of the plasma biomarkers.

3. The method according to any one of claims 1 to 2, wherein the plasma biomarker is measured directly in plasma using liquid-phase multianalyte profiling technology.

4. The method according to any one of claims 1 to 3, wherein the one or more plasma biomarkers measured in the subject are compared to a corresponding reference value; the presence of HS is determined according to the one or more plasma biomarkers whose value is significantly increased or decreased from the corresponding reference value.

5. The method according to claim 4, wherein the one or more plasma biomarkers include IL-8, and the amount of IL-8 is higher than the corresponding reference value in the subject.

6. The method according to claim 4 or 5, wherein the one or more plasma biomarkers include TNFα, and the amount of TNFα is higher than the corresponding reference value in the subject.

7. The method according to any one of claims 4 to 6, wherein the one or more plasma biomarkers include IL36β, and the amount of IL36β is lower than the corresponding reference value in the subject.

8. The method according to any one of claims 4 to 7, wherein the one or more plasma biomarkers include MDC, and the amount of MDC is lower than the corresponding reference value in the subject.

9. The method according to any one of claims 4 to 8, wherein the corresponding reference value for one or more plasma biomarkers is the amount of the corresponding plasma biomarker in a healthy subject.

10. A method for treating an object having HS, Examining the HS in a subject according to the method described in any one of claims 1 to 9; and A method comprising treating the subject by administering one or more therapeutically effective doses of drugs for the treatment of HS.

11. The method according to claim 10, wherein the test results are an indicator for the treatment of HS.

12. The method according to claim Error! Reference source not found., wherein TNFα is approximately 1 to 3 times higher in the subject having HS; IL36β is approximately 25% to approximately 75% lower in the subject having HS; IL8 is approximately 2 to 4 times higher in the subject having HS; and MDC is approximately 10% to approximately 50% lower in the subject having HS.

13. The method according to any one of claims 10 to 12, wherein the examination of HS in the subject is a companion diagnostic examination performed before treating the subject, and the results of the examination are indicators for treating HS.

14. The method according to any one of claims 10 to 13, wherein the one or more drugs are selected from the group consisting of C5aR inhibitors, C5a inhibitors, adalimumab, antibiotics, retinoids, spironolactone or finasteride and metformin.

15. The aforementioned drug is a C5aR inhibitor of formula I: 【Chemistry 11】 or a pharmaceutically acceptable salt thereof, In the formula, each R １ CH ３ CF ３ ,CH ２ CH ３ , Cl, 1-pyrrolidine, -O-CH(CH ３ ) ２ and CH ２ Independently selected from the group consisting of OH; Each R ２ is independently selected from the group consisting of CH ３ and F; The method according to claim 14, wherein the effective dose of formula I to be administered is 15 mg to about 60 mg twice daily.

16. The compound is, 【Chemistry 12】 The method according to claim 14, wherein the abacopan having or a pharmaceutically acceptable salt thereof.

17. The method according to claim 16, wherein the effective treatment dose of the compound to be administered is approximately 30 mg twice a day.

18. A method for measuring the disease severity of HS in a subject, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of APRIL, BAFF, C5b-9, CD25, IL6, IL8, and S100A8 / 89.

19. A method for measuring the disease severity of HS in a subject according to claim 18, the method comprising measuring two or more of the plasma biomarkers.

20. A method for measuring the disease severity of HS in a subject according to claim 18, the method comprising measuring three or more of the plasma biomarkers.

21. A method for measuring the disease severity of HS in a subject according to any one of claims 18 to 20, wherein one or more plasma biomarkers measured in the subject are compared to a corresponding reference value; and the disease severity of HS is determined according to one or more plasma biomarkers whose value is significantly increased or decreased from the corresponding reference value.

22. A method for measuring the disease severity of HS in a subject according to claim 21, wherein the one or more plasma biomarkers include APRIL, and an amount of APRIL in the subject lower than the corresponding reference value indicates a more severe HS.

23. A method for measuring the disease severity of HS in a subject according to claim 21 or 22, wherein the one or more plasma biomarkers include BAFF, and a lower amount of BAFF in the subject than the corresponding reference value indicates a more severe HS.

24. A method for measuring the disease severity of HS in a subject according to any one of claims 21 to 23, wherein the one or more plasma biomarkers include C5b-9, and a lower amount of C5b-9 in the subject than the corresponding reference value indicates a more severe HS.

25. A method for measuring the disease severity of HS in a subject according to any one of claims 21 to 24, wherein the one or more plasma biomarkers include CD25, and a lower amount of CD25 in the subject than the corresponding reference value indicates a more severe HS.

26. A method for measuring the disease severity of HS in a subject according to any one of claims 21 to 25, wherein the one or more plasma biomarkers include IL-6, and a higher amount of IL-6 in the subject than the corresponding reference value indicates a more severe HS.

27. A method for measuring the disease severity of HS in a subject according to any one of claims 21 to 26, wherein the one or more plasma biomarkers include IL-8, and a higher amount of IL-8 in the subject than the corresponding reference value indicates a more severe HS.

28. A method for measuring the disease severity of HS in a subject according to any one of claims 21 to 27, wherein the one or more plasma biomarkers include S100A8 / 89, and a higher amount of S100A8 / 89 in the subject than the corresponding reference value indicates a more severe HS.

29. A method for measuring the disease severity of HS in a subject according to any one of claims 20 to 27, wherein the corresponding reference value of one or more plasma biomarkers is the amount of the corresponding plasma biomarker in a healthy subject.

30. A method for treating a subject with Hurley stage III disease, comprising: Measuring the disease severity of HS according to the method described in any one of claims 18 to 29; and A method comprising treating the subject by administering one or more drugs in a therapeutically effective dose for the treatment of Hurley stage III.

31. A method for treating a subject having Hurley stage III according to claim 30, wherein the result of the measurement of disease severity of HS is an indicator for the treatment of Hurley stage III.

32. The method according to any one of claims 30 or 31, wherein the measurement of disease severity of HS is a companion diagnostic test performed before treating the subject, and the results of the test are an indicator for the treatment of Hurley stage III.

33. A method for treating a subject having Hurley stage III according to any one of claims 30 to 32, wherein the plasma biomarker is measured by a multianalyte assay.

34. A method for treating a subject having Hurley stage III according to any one of claims 30 to 33, wherein the measured value of the plasma biomarker is compared to a corresponding reference value; and the severity of HS is determined according to the Hurley clinical staging system as determined by a physician.

35. A method for treating a subject having Hurley stage III according to any one of claims 30 to 34, wherein the agent is selected from the group consisting of a C5aR inhibitor, a C5a inhibitor, adalimumab, an antibiotic, a retinoid, spironolactone or finasteride, and metformin.

36. A method for treating a subject having Hurley stage III according to claim 35, wherein the agent is a C5aR inhibitor of formula I: 【Chemistry 13】 or a pharmaceutically acceptable salt thereof, In the formula, each R １ CH ３ CF ３ ,CH ２ CH ３ , Cl, 1-pyrrolidine, -O-CH(CH ３ ) ２ and CH ２ Independently selected from the group consisting of OH; Each R ２ CH ３ and independently selected from the group consisting of F; The effective dose of Formula I administered is 15 mg to approximately 60 mg twice daily.

37. A method for treating a subject having Hurley stage III according to claim 36, wherein the compound is of formula 【Chemistry 14】 A method comprising abacopan or a pharmaceutically acceptable salt thereof having [a specific compound].

38. A method for treating a subject having Hurley stage III as described in claim 37, wherein the effective dose of the compound administered is about 30 mg twice daily.

39. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective in treating HS, comprising measuring one or more plasma biomarkers in a sample taken from the subject, wherein the one or more plasma biomarkers are selected from the group consisting of CD25, complement factor B, IL8, NGAL, S100A8 / A9, and VEGF.

40. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS as described in claim 39, the method comprising measuring two or more of the plasma biomarkers.

41. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS as described in claim 39, the method comprising measuring three or more of the plasma biomarkers.

42. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS according to any one of claims 39 to 41, wherein the plasma biomarker is measured by a multianalyte assay.

43. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS according to any one of claims 39 to 42, wherein the biomarker is used to lead to a biomarker test that can be performed on an HS patient to indicate treatment with the drug.

44. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with an agent effective for treating HS according to any one of claims 39 to 43, wherein the agent is selected from the group consisting of a C5aR inhibitor, a C5a inhibitor, adalimumab, an antibiotic, a retinoid, spironolactone or finasteride and metformin.

45. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS according to claim 44, wherein the drug is a C5aR inhibitor of formula I: 【Chemistry 15】 or a pharmaceutically acceptable salt thereof, In the formula, each R １ CH ３ CF ３ ,CH ２ CH ３ , Cl, 1-pyrrolidine, -O-CH(CH ３ ) ２ and CH ２ Independently selected from the group consisting of OH; Each R ２ CH ３ and independently selected from the group consisting of F; The effective dose of Formula I administered is 15 mg to approximately 60 mg twice daily.

46. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS according to claim 45, wherein the compound is: 【Chemistry 16】 A method comprising abacopan or a pharmaceutically acceptable salt thereof having [a specific compound].

47. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS as described in claim 46, wherein the effective dose of the compound administered is about 30 mg twice daily.

48. A method for treating a subject having Hurley stage III as described in claim 35, wherein the agent is selected from the group consisting of INF904, viroberimab, and IFX002.

49. A method for measuring the clinical response rate (HiSCR) of HS in a subject having HS treated with a drug effective for treating HS as described in claim 44, wherein the drug is selected from the group consisting of INF904, viroberimab, and IFX002.

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