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

• Published in: The Journal of dermatological treatment Vol. 29; no. 1; pp. 13 - 18
• Main Authors: Hohenberger, Megan, Cardwell, Leah A., Oussedik, Elias, Feldman, Steven R.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-01-2018
• Subjects: Animals; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Biologics; brodalumab; Clinical Trials as Topic; Colitis, Ulcerative - epidemiology; Colitis, Ulcerative - etiology; Crohn Disease - epidemiology; Crohn Disease - etiology; Humans; Inflammatory Bowel Diseases - epidemiology; Inflammatory Bowel Diseases - etiology; Interleukin-17 - antagonists & inhibitors; Interleukin-17 - genetics; Interleukin-17 - immunology; ixekizumab; Mice; Mice, Knockout; Psoriasis - drug therapy; secukinumab; ixekizumab; Biologics; brodalumab; secukinumab
• ISSN: 0954-6634; 1471-1753
• DOI: 10.1080/09546634.2017.1329511

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.