Tofacitinib and newer JAK inhibitors in inflammatory bowel disease—where we are and where we are going

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Abstract

Inflammatory bowel diseases, comprising ulcerative colitis (UC) and Crohn’s disease, are chronic, immune-mediated and progressive inflammatory disorders affecting the gastrointestinal tract. Tofacitinib is the first oral small-molecule Janus kinase (JAK) inhibitor licensed and approved by the National Institute for Health and Care Excellence (NICE) for use in moderately-to-severely active UC after intolerance, inadequate response, or loss of response to conventional treatment or biologic therapy. The pivotal OCTAVE studies demonstrated the efficacy and safety of tofacitinib for the induction and maintenance of remission in UC. A growing body of evidence from real-world data supports the positive clinical and endoscopic benefits observed with tofacitinib treatment in the OCTAVE trials. This narrative review summarizes the current literature regarding the mechanism of action of tofacitinib, data from registrational trials, emerging real-world evidence, and an overview of the most recent safety evidence. We explore evolving treatment paradigms including the use of tofacitinib in the COVID-19 era, pregnancy and extraintestinal manifestations as well as the emerging concept of combining tofacitinib with biological therapy. We will also present a brief overview of the next generation of JAK inhibitors in the pipeline.

Keywords: Crohn’s disease, effectiveness, efficacy, inflammatory bowel diseases, Janus kinase inhibitors, ulcerative colitis, safety, tofacitinib.

Citation: Liu E, Aslam N, Nigam G, Limdi JK. Tofacitinib and newer JAK inhibitors in inflammatory bowel disease – where we are and where we are going. Drugs Context. 2022;11:2021-11-4. https://doi.org/10.7573/dic.2021-11-4

Contributions: EL, NA, GN and JKL coauthored the initial draft of the manuscript. JKL subsequently revised and edited the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICJME) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: EL and JKL have a non-pharmaceutical investigator-initiated sponsored research grant from Galapagos. EL has received speaker fees from Janssen. JKL has received speaker and consultancy fees from Abbvie, Arena, MSD, Galapagos, Janssen, Takeda, Pfizer and Tillots, and research support from Galapagos and Takeda. EL has received speaker fees from Janssen. The authors declare that they have no other conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/03/dic.2021-11-4-COI.pdf

Acknowledgements: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2022 Liu E, Aslam N, Nigam G, Limdi JK. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0, which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2022 Liu E, Aslam N, Nigam G, Limdi JK. https://doi.org/10.7573/dic.2021-11-4. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/tofacitinib-and-newer-jak-inhibitors-in-inflammatory-bowel-disease-where-we-are-and-where-we-are-going

Correspondence: Jimmy K Limdi, IBD Clinical Research Unit, Fairfield General Hospital, The Northern Care Alliance NHS Foundation Trust, Rochdale Old Road, Bury, Manchester BL9 7TD, UK. Email: jimmy.limdi@nhs.net

Provenance: Invited; externally peer reviewed.

Submitted: 11 November 2021; Accepted: 4 March 2022; Publication date: 8 April 2022.

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