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Review
JAK inhibitors for inflammatory bowel disease: recent advances
  1. Sailish Honap1,2,
  2. Alexandra Agorogianni1,
  3. Michael J Colwill1,
  4. Sonia Kalyanji Mehta1,
  5. Fiona Donovan1,
  6. Richard Pollok1,3,
  7. Andrew Poullis1,
  8. Kamal Patel1
  1. 1Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, London, UK
  2. 2School of Immunology and Microbial Sciences, King's College, London, UK
  3. 3Institute of Infection and Immunity, St George's University, London, UK
  1. Correspondence to Dr Sailish Honap, Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, London, SW17 0QT, UK; shonap{at}nhs.net

Abstract

Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn’s disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.

  • IBD CLINICAL
  • INFLAMMATORY BOWEL DISEASE
  • ULCERATIVE COLITIS
  • CROHN'S DISEASE

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Footnotes

  • Contributors SH and KP conceived the idea. SH wrote the original draft. SH, AA, MJC, SKM and FD were involved in the planning, conduct and reporting of the work. All authors critically reviewed and edited the manuscript before submission. SH is responsible for the overall content as guarantor.

  • 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 SH has served as a speaker, a consultant and/or advisory board for Pfizer, Janssen, Abbvie and Takeda, has received educational grants from Dr. Falk Pharma, Pharmacosmos and Ferring, and has had research supported by Pfizer. SKM has received speaker fees and/or advisory board fees from Dr. Falk Pharma. KP has received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, Dr. Falk Pharma, PredictImmune, Pfizer and Ferring and has received advisory board fees from Abbvie, Galapagos, Pfizer, and Janssen. AA, MJC, FD, RP and AP report no conflicts.

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