Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease

Abstract

Introduction: Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials.

Aim: To characterize the relationship between IL-17 inhibition and inflammatory bowel disease.

Methods: A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab.

Results: IL-17 A inhibition, IL-17RA inhibition and IL-17 knockout led to induction or exacerbation of colitis in mouse models. The placebo groups fared better than the treatment group in controlled trials of anti-IL-17 antibody and anti-IL-17 receptor for Crohn’s disease (CD). A brodalumab study (N = 1576) revealed one reported CD case. An ixekizumab study (N = 3736) evaluating moderate-to-severe psoriasis, four patients reported CD and seven reported UC while ixekizumab every 2 weeks led to a moderate exacerbation of UC in one patient and new-onset CD in one patient. A secukinumab study (N = 3430) revealed exposure adjusted incidence rates of 0.11 and 0.15 per 100 patient-years for CD and UC, respectively.

Discussion: Anti-IL-17 medications are associated with IBD exacerbation. Caution should be used in prescribing these medications in patients with diagnosed IBD or personal history suggestive of IBD.

Keywords:

• Biologics
• secukinumab
• ixekizumab
• brodalumab

Disclosure statement

Dr. Feldman is a speaker for Janssen and Taro. He is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Leo Pharma Inc. He is a consultant for Amgen, Baxter, Caremark, Gerson Lehrman Group, Guidepoint Global, Hanall Pharmaceutical Co Ltd, Kikaku, Lilly, Merck & Co Inc, Merz Pharmaceuticals, Mylan, Novartis Pharmaceuticals, Pfizer Inc, Qurient, Suncare Research and Xenoport. He is on an advisory board for Pfizer Inc. Dr. Feldman is the founder and holds stock in Causa Research and holds stock and is majority owner in Medical Quality Enhancement Corporation. He receives Royalties from UpToDate and Xlibris.

Leah A. Cardwell, Megan Hohenberger and Elias Oussedik have no conflicts of interest to disclose.

Contents of the manuscript have not been previously published and are not currently submitted elsewhere.