IL‐17A is a pertinent therapeutic target for moderate‐to‐severe hidradenitis suppurativa: Combined results from a pre‐clinical and phase II proof‐of‐concept study. Issue 10 (19th August 2022)

• Record Type: Journal Article
• Authors: Kimball, Alexa B.; Loesche, Christian; Prens, Errol P.; Bechara, Falk G.; Weisman, Jamie; Rozenberg, Izabela; Jarvis, Philip; Peters, Thomas; Roth, Lukas; Wieczorek, Grazyna; Kolbinger, Frank; Jemec, Gregor B. E.
• Is Part Of: Experimental dermatology. Volume 31:Issue 10(2022)
• Page Start: 1522
• Page End: 1532
• Publication Date: 2022-08-19
• Subjects: clinical trial -- hidradenitis suppurativa -- IL‐17A -- pathophysiology -- T cells; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.14619
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: Hidradenitis Suppurativa (HS) is a chronic, recurrent, inflammatory, follicular skin disease whose pathology is complex and not fully understood. The objective of this study was to elucidate the role of IL‐17A in moderate‐to‐severe HS. Transcriptomic and histological analyses were conducted on ex vivo HS ( n = 19; lesional and non‐lesional) and healthy control ( n = 8) skin biopsies. Further, a Phase II exploratory, randomized, double‐blind, placebo‐controlled study was carried out in moderate‐to‐severe HS patients. Patients were treated with either CJM112 300 mg ( n = 33), a fully human anti‐IL‐17A IgG1/κ monoclonal antibody, or placebo ( n = 33). The main outcome of the translational analyses was to identify IL‐17A‐producing cells and indications of IL‐17A activity in HS lesional skin. The primary objective of the clinical study was to determine the efficacy of CJM112 in moderate‐to‐severe HS patients by HS‐Physician Global Assessment (HS‐PGA) responder rate at Week 16. Transcriptomic and histopathologic analyses revealed the presence of heterogeneous cell types in HS lesional skin; IL‐17A gene signatures were increased in HS lesional vs non‐lesional or healthy skin. High expression of IL‐17A was localized to T cells, neutrophils, and mast cells, confirming the transcriptional data. Clinically, the proportion of Week 16 HS‐PGA responders was significantly higher ( p = 0.03) in the CJM112 group vs placebo (32.3% vs 12.5%). This study elucidated the role of the IL‐17A pathway in HS pathogenesis and clinically validated the IL‐17A pathway in moderate‐to‐severe HS patients in a proof‐of‐concept study using the anti‐IL‐17A‐specific antibody CJM112.