Is 2nd JAKi treatment for UC worth the effort? A retrospective, multi-centre UK study

Abstract

Background and Aims: Janus kinase inhibitors (JAKi) provide effective treatment for ulcerative colitis (UC), but inadequate response (IR) or intolerance occurs frequently. This study aimed to assess the effectiveness of a second JAKi in a real-world UC cohort. Method(s): A retrospective multicenter cohort study encompassing 19 UK hospitals was undertaken. Primary outcome was clinical remission (Simple Clinical Colitis Activity Index/partial Mayo Score=3 advanced therapies and 50% required corticosteroids at induction. Clinical remission rates were 59% and 51% at weeks 8 and 24. Biochemical and endoscopic remission rates were 61% and 60% at week 8, and 47% and 32% at week 24. All disease activity parameters significantly reduced by week 8 (P<.001). At week 24 no difference was detected in clinical remission rates between those with primary non-response (42%) or secondary loss of response (52%) to their first JAKi (P=.518). Clinical remission did not differ between upadacitinib (54%) and filgotinib (36%), P=.253. Adverse events occurred in 27% of patients, and serious adverse events in 8%. Conclusion(s): In this highly refractory cohort with active UC a second JAKi effectively achieved remission following IR to first JAKi. Type of first JAKi failure did not appear to influence clinical remission. No new safety signals were found.Copyright © The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.