Gastroenterological safety of IL-17 inhibitors: a systematic literature review

ABSTRACT

Introduction

Interleukin 17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of many chronic immune-mediated disorders. Interleukin 17 inhibitors provide an excellent treatment option for patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. However, Interleukin 17 inhibitors have been suspected of worsening or triggering new-onset inflammatory bowel disease.

Areas covered

A literature search was conducted until March 2021 to investigate reporting prevalence, and characteristics of all gastroenterological adverse events in patients treated with Interleukin 17 inhibitors. One hundred and six clinical randomized trials were included, involving 40,053 patients. Inflammatory bowel disease cases were reported in 0.4% of patients exposed to Interleukin 17 inhibitors. The most frequent other gastrointestinal adverse events were diarrhea (2.5%), nausea or vomiting (0.7%), and gastroenteritis (0.2%). Sixty-one uncontrolled or retrospective studies were included, involving 16,791 patients. Sixty (0.36%) inflammatory bowel disease cases were reported, 0.6% of patients reported other gastrointestinal adverse events.

Expert opinion

Interleukin 17 inhibitors are safe and effective in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Low incidence rate of developing new-onset inflammatory bowel disease or exacerbating preexisting inflammatory bowel disease with anti-IL-17 agents has been reported. Clinicians should be aware of the possibility of these concerns when considering this therapy.

KEYWORDS:

• IL-17 inhibitor
• secukinumab
• ixekizumab
• brodalumab
• Crohn’s disease
• ulcerative colitis
• safety

Article highlights

• Treatment with IL-17 inhibitors is associated with a low incidence of inflammatory bowel disease in patients with rheumatological and dermatological auto-immune diseases in both clinical trials and clinical practice.

• The most frequent gastrointestinal adverse events are diarrhoea, nausea and/or vomiting, and gastroenteritis.

• The onset of digestive adverse events cannot be neglected and requires continuous and careful monitoring.

• Physicians should pay close attention to patients’ previous intestinal disorders before prescribing IL-17 inhibitors.

Abbreviations

CD (Crohn’s Disease), CI (Confidence Interval), FC (Fecal Calprotectin), IBD (Inflammatory Bowel Disease), IL (Interleukin), IMID (Immune-Mediated Inflammatory Disease), RD (Risk Difference), TH17 (T helper 17), TNF (Tumor Necrosis Factor), UC (Ulcerative Colitis)

Data availability statement

The data underlying this article are available in the paper and in its online supplementary material.

Declaration of interest

B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, and Takeda. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis and Theravance. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are an employee of Mount Sinai and receives research funds from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc.; and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.