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 and Jemec, Gregor BE (2022) 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. Experimental dermatology, 31 (10). pp. 1522-1532. ISSN 1600-0625

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.

Item Type:	Article
Keywords:	Antibodies, Monoclonal Dermatitis Hidradenitis Suppurativa Humans Immunoglobulin G Prostaglandins A Skin
Date Deposited:	08 Nov 2022 00:45
Last Modified:	08 Nov 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45427