Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review

Abstract

The IL-17 pathway is a potential therapeutic target shown to be implicated in hidradenitis suppurativa (HS), however, it remains unclear whether evidence from mechanistic studies may translate into clinical practice. This systematic review summarizes available treatment outcomes of IL-17 inhibitors in patients with HS. Embase, MEDLINE, PubMed, and clinicaltrials.gov were comprehensively searched on February 26, 2021 to include 16 original studies representing 128 patients with HS (mean age: 36.5 years; age range: 21-47 years; male: 50.0%). Treatment outcomes were reported for the following biologics: secukinumab ( n = 105), brodalumab ( n = 22), and ixekizumab ( n = 1). Patients were classified as responders or non-responders according to achievement of a positive response/improvement based on criteria established for each included study. For secukinumab 57.1% ( n = 60/105) of patients were responders in a mean response period of 16.2 weeks and 42.9% ( n = 45/105) were non-responders; for brodalumab, 100.0% ( n = 22/22) of patients were responders within 4.4 weeks; and the one patient treated with ixekizumab was a responder within 10 weeks. In conclusion, IL-17 inhibitors may serve as an effective therapeutic target in approximately two-thirds of patients with HS and can be considered in those who are refractory to other treatment modalities. We also stress the importance of consistent outcome measures to enhance evidence synthesis, decrease reporting bias, provide potential for future meta-analysis, and ultimately improve clinical outcomes for patients with HS.

IL-17 and IL-17-producing cells in protection versus pathology

“…Hidradenitis suppurativa, a chronic inflammatory skin disease of hair follicles, is characterized by substantial skin infiltration of T H 17 cells that express CD161, a lineage marker for T H 17 cells 135 . Open-label pilot clinical trials with secukinumab showed moderate efficacy in patients with hidradenitis suppurativa 136 , and phase III trials are ongoing. Although secukinumab was not effective in treating alopecia areata 137 , there is off-label use of IL-17-blocking drugs for the treatment other skin disorders, including Behcet disease, lichen planus, pustular psoriasis, impetigo herpetiformis and pityriasis rubra pilaris.…”

An Anti-Interleukin-17A Monoclonal Antibody, Ixekizumab, in the Treatment of Resistant Hidradenitis Suppurativa: A Case Series

“…While data are increasing regarding secukinumab and brodalumab, the literature on ixekizumab is limited [4, 6-8]. Ixekizumab, a humanized monoclonal immunoglobulin G 4 antibody, specifically binding to IL-17A, is very effective in treating moderate to severe psoriasis [4]. We found 3 case reports of ixekizumab for HS.…”

“…The IL-17 pathway has been implicated as a potential therapeutic target in HS, prompting clinical trials with various IL-17 inhibitors (secukinumab, brodalumab, and ixekizumab) [4]. While data are increasing regarding secukinumab and brodalumab, the literature on ixekizumab is limited [4,[6][7][8].…”

“…The IL-17 pathway has been implicated as a potential therapeutic target in HS, prompting clinical trials with various IL-17 inhibitors (secukinumab, brodalumab, and ixekizumab) [4]. While data are increasing regarding secukinumab and brodalumab, the literature on ixekizumab is limited [4,[6][7][8]. Ixekizumab, a humanized monoclonal immunoglobulin G 4 antibody, specifically binding to IL-17A, is very effective in treating moderate to severe psoriasis [4].…”

“…Although the pathogenesis of HS has not been fully elucidated, aberrant expression of pro-inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-1β, and IL-17 play a central role [2,3]. Adalimumab is the only approved biologic for the treatment of HS; many other biological agents, including IL-17 inhibitors, appear promising [4,5]. There are case reports of HS improved with ixekizumab [6][7][8].…”