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Review
Paradoxical gastrointestinal effects of interleukin-17 blockers
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  1. Marine Fauny1,
  2. David Moulin2,
  3. Ferdinando D'Amico3,4,
  4. Patrick Netter2,
  5. Nadine Petitpain5,
  6. Djesia Arnone4,
  7. Jean-Yves Jouzeau2,
  8. Damien Loeuille1,2,
  9. Laurent Peyrin-Biroulet4
  1. 1 Rheumatology Department, University Hospital of Nancy, Nancy, France
  2. 2 Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Nancy, France
  3. 3 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
  4. 4 Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
  5. 5 Regional Centre of Pharmacovigilance, University Hospital of Nancy, Nancy, France
  1. Correspondence to Professor Laurent Peyrin-Biroulet, Inserm NGERE and Department of Gastroenterology Nancy University Hospital, University of Lorraine 1 Allée du Morvan, 54511 Vandoeuvre-lès-Nancy, France; peyrinbiroulet{at}gmail.com

Abstract

Secukinumab, ixekizumab and brodalumab are monoclonal antibody therapies that inhibit interleukin (IL)-17 activity and are widely used for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. The promising efficacy results in dermatology and rheumatology prompted the evaluation of these drugs in Crohn’s disease and ulcerative colitis, but the onset of paradoxical events (disease exacerbation after treatment with a theoretically curative drug) prevented their approval in patients with inflammatory bowel diseases (IBDs). To date, the pathophysiological mechanisms underlying these paradoxical effects are not well defined, and there are no clear guidelines for the management of patients with disease flare or new IBD onset after anti-IL-17 drug therapy. In this review, we summarise the literature on putative mechanisms, the clinical digestive effects after therapy with IL-17 inhibitors and provide guidance for the management of these paradoxical effects in clinical practice.

  • arthritis, psoriatic
  • spondylitis, ankylosing
  • biological therapy

https://doi.org/10.1136/annrheumdis-2020-217927

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors MF, DM, PN, NP, FD, DA, J-YJ, and DL selected the studies and wrote the article. LP-B conceived and critically revised the manuscript. The manuscript was approved by all authors.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests LP-B 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, Boehringer-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.