Editorial: JAK to JAK—Navigating Intra-Class JAK Inhibitor Switching in Inflammatory Bowel Disease. Authors' Reply

Abstract

We thank Clough et al. for their editorial, which highlights the importance of the real-world data we generated on intra-class Janus kinase inhibitors (JAKi) switching [1, 2]. It is also important to note that this strategy may be of interest for patients with difficult-to-treat inflammatory bowel disease (IBD), although most currently available evidence assessed the switch from tofacitinib to upadacitinib [3]. Various studies, including ours, confirm the potential benefit of this approach, with approximately one in two patients achieving clinical remission after the induction phase. Similarly, the safety profile appears acceptable in patients previously exposed to multiple lines of immunomodulators.

There is less evidence supporting intra-class JAKi switching for sequences other than tofacitinib-to-upadacitinib in IBD. However, studies including rheumatoid arthritis have provided evidence to support cycling to another JAKi in case of inadequate response to a first JAKi besides tofacitinib [4].

Additionally, switching in patients intolerant to a first-line JAKi could be considered. Indeed, the safety profiles of the three available JAKi differ [5], and both safety and efficacy appear to be dose-related and intercorrelated. Therefore, a second-line JAKi could be proposed after discontinuation of a first-line JAKi that was effective but poorly tolerated. For instance, switching to tofacitinib or filgotinib could be an option in a patient receiving upadacitinib that is effective for colonic inflammatory activity but associated with severely burdensome acne. Acne is more frequent with upadacitinib than other JAKi [6].

As we emphasised in our paper, all intra-class switching strategies within the JAKi class should be carefully considered; future studies will be necessary to support the various potential approaches.

Mathieu Uzzan: writing – original draft, conceptualization. David Laharie: writing – review and editing. Julien Kirchgesner: writing – review and editing.

M.U. declares counselling, boards or fees for AbbVie, Amgen, Celltrion, Pfizer, Owkin, Janssen, Lilly, Takeda. D.L. declares counselling, boards, transports or fees from Abbvie, Alfasigma, Amgen, Celltrion, Ferring, Janssen, Lilly, Medac, MSD, Pfizer, Sandoz, Takeda. J.K. received lecture fees from Janssen and Lilly, and consulting fees from Roche, Pfizer, Janssen, Abbvie, Takeda, Lilly, and Gilead.

This article is linked to Osty et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70199 and https://doi.org/10.1111/apt.70226.