Background and aimsJanus 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.MethodsA retrospective multicenter 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 fecal calprotectin ≤ 200µg/g) and endoscopic (Ulcerative Colitis Endoscopic Index of Severity/Mayo Endoscopic Subscore ≤ 1) remission were also assessed.ResultsA total of 131 patients with active UC were included. The 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 < .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%.ConclusionsIn 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.