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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 effectiveness of a second JAKi in a real-world UC cohort. Methods: A retrospective multicentre cohort study encompassing 19 UK hospitals was undertaken. Primary outcome was clinical remission (Simple Clinical Colitis Activity Index/partial Mayo Score ≤ 1) at weeks 8 and 24, based on available assessments. Biochemical (CRP ≤ 5mg/L and faecal calprotectin ≤ 200µg/g) and endoscopic (Ulcerative Colitis Endoscopic Index of Severity/Mayo Endoscopic Subscore ≤ 1) remission were also assessed. Results: 131 patients with active UC were included. Majority (60%) had exposure to ≥ 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 < 0.001). 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 = 0.518). Clinical remission did not differ between upadacitinib (54%) and filgotinib (36%), p = 0.253. Adverse events occurred in 27% of patients, and serious adverse events in 8%. Conclusions: 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.
Author
Radia, Chandni
Danso, Yaa
Ritchie, Susan
Hale, Melissa
Elford, Alexander T
Patel, Chirag
Hicks, Lucy
Kalyanji, Sonia
Dong, Chaonan
Yeung, Katie
Yeo, Jie Han
Allah-Ditta, Mohammed
Bishara, Maria
Sethi-Arora, Karishma
Pillay, Lushen
Johnston, Emma L
Rudling, Ruth
Rees, Fiona
Harvey, Philip
Trodden-Mittnacht, Hannah
Davis, Emma
Fraser, Aileen
Sawan, Nitish Jivan
Hussain, Muhammad Azhar
Campbell, Roisin
George, Becky
Rawcliffe, Megan
Choon, Xin Yi
Shah, Krishna
Al-Zarrad, Dania
Toft, Jennifer
Chhabra, Puneet
Burr, Nick
Hewitt, Alice
Kumar, Rohith
McCartney, Sara
Rosiou, Konstantina
Dhar, Anjan
Lees, Charlie W
Lamb, Christopher A
Speight, Ally
Ahmad, Tariq
Limdi, Jimmy
Raine, Tim
Walsh, Alissa
Cooney, Rachel
Harrow, Paul
Patel, Kamal
Samaan, Mark
Pavlidis, Polychronis
Kent, Alexandra
Selinger, Christian
Kok, Klaartje
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Date
2025-08-20
Type
Article
Subject
Inflammatory bowel diseases, Enzyme inhibitors, Remission induction, Multicentre studies as a topic
Collections
UHB Gastroenterology
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Citation
Radia C, Danso Y, Ritchie S, Hale M, Elford AT, Patel C, Hicks L, Kalyanji S, Dong C, Yeung K, Yeo JH, Allah-Ditta M, Bishara M, Sethi-Arora K, Pillay L, Johnston EL, Rudling R, Rees F, Harvey P, Trodden-Mittnacht H, Davis E, Fraser A, Sawan NJ, Hussain MA, Campbell R, George B, Rawcliffe M, Choon XY, Shah K, Al-Zarrad D, Toft J, Chhabra P, Burr N, Hewitt A, Kumar R, McCartney S, Rosiou K, Dhar A, Lees CW, Lamb CA, Speight A, Ahmad T, Limdi J, Raine T, Walsh A, Cooney R, Harrow P, Patel K, Samaan M, Pavlidis P, Kent A, Selinger C, Kok K. Is 2nd JAKi treatment for UC worth the effort? A retrospective, multi-Centre UK study. J Crohns Colitis. 2025 Aug 20:jjaf154. doi: 10.1093/ecco-jcc/jjaf154.
Journal / Source Title
Journal of Crohn's & colitis
DOI
10.1093/ecco-jcc/jjaf154
URI
https://mider.dspace7.openrepository.com/handle/20.500.14200/8386
PMID
40833970
Publisher
Oxford University Press
Publisher’s URL
https://academic.oup.com/ecco-jcc
Publisher’s statement
Note / Copyright