Chandni Radia, Yaa Danso, Susan Ritchie, Melissa Hale, Alexander T Elford, Chirag Patel, Lucy Hicks, Sonia Kalyanji, Chaonan Dong, Katie Yeung, Jie Han Yeo, Mohammed Allah-Ditta, Maria Bishara, Karishma Sethi-Arora, Lushen Pillay, Emma L Johnston, Ruth Rudling, Fiona Rees, Philip Harvey, Hannah Trodden-Mittnacht, Emma Davis, Aileen Fraser, Nitish Jivan Sawan, Muhammad Azhar Hussain, Roisin Campbell, Becky George, Megan Rawcliffe, Xin Yi Choon, Krishna Shah, Dania Al-Zarrad, Jennifer Toft, Puneet Chhabra, Nick Burr, Alice Hewitt, Rohith Kumar, Sara McCartney, Konstantina Rosiou, Anjan Dhar, Charlie W Lees, Christopher A Lamb, Ally Speight, Tariq Ahmad, Jimmy Limdi, Tim Raine, Alissa Walsh, Rachel Cooney, Paul Harrow, Kamal Patel, Mark Samaan, Polychronis Pavlidis, Alexandra Kent, Christian Selinger, Klaartje Kok
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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.
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