P0706Effectiveness and safety of switching from a first JAKi to a subsequent JAKi in patients with ulcerative colitis: preliminary retrospective data from IG-IBD multicentre cohort study

Abstract Background Janus kinase inhibitors (JAKi) are a class of oral therapies indicated for moderate-to-severe ulcerative colitis (UC), with three agents approved and broadly comparable efficacy and safety. Although no clear evidence shows that differences in target affinity influence response, switching to a second JAKi is sometimes attempted after failure or intolerance to the first. The main objective is to assess the effectiveness (defined as treatment persistence) and safety of a second JAKi after failure of the first one Methods This retrospective analysis is part of a 12-month, multicentre, ambispective observational study. We included patients who initiated a second JAKi less than 24 months prior to enrolment, following a first-line JAKi course. Demographics, disease features, and clinical, biochemical, and endoscopic data at baseline and at weeks 8, 26, and 52 were recorded in a REDCap database. Data are presented as frequencies and percentages. Treatment persistence was estimated with Kaplan–Meier survival analysis, and rates are reported both as observed and with non-responder imputation (NRI). Safety events were collected throughout follow-up. Recruitment for both retrospective and prospective phases is ongoing and will end in April 2026; this abstract presents preliminary. Results Data from 69 UC patients are currently available: median age 40 years (IQR 27–52) ; 30 (43. 5%) females. Mean disease duration was 10. 8±7. 9 years. Disease extent: proctitis 3 (4. 3%), left-sided colitis 29 (42. 0%), extensive colitis 37 (53. 7%). Eight patients (11. 6%) were smokers, and 11. 6% had other cardiovascular risk factors. Most patients (40, 57. 9%) had prior exposure to ≥ 3 biologics or small molecules. Tofacitinib was the most common first JAKi (48, 69. 6%) prescribed; among those who switched from tofacitinib, 9 (24. 3%) moved to filgotinib and 28 (75. 7%) to upadacitinib. Reasons for discontinuing the first JAKi were secondary loss of response in 42 patients (62%), primary non-response in 24 (34%), and intolerance in 3 patients (4%). At baseline, the mean Partial Mayo score was 5. 1±2. 3, and 20 (29%) were on systemic steroids. At week 26, treatment persistence was 87. 0% (47/54) as observed and 68. 1% (47/69) with NRI; at week 52 it was 85. 1% (40/47) as observed and 58. 0% (40/69) with NRI. Six patients experienced adverse drug reactions, none leading to discontinuation Conclusion Our preliminary findings suggest that switching from a first to a subsequent JAKi is effective and safe, including for patients with prior exposure to multiple biologic therapies. Further retrospective and prospective analyses will provide more precise estimates References: - Danese S, Vermeire S, Zhou W, et al. 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Rev. 2020;7: 189–205. doi: 10. 17294/2330-0698. 1722 Conflict of interest: Dr. Mendolaro, Marco: No conflict of interest Viola, Anna: No conflict of interest Ferracane, Concetta: No conflict of interest De Bernardi, Alice: No conflict of interest Savarino, Edoardo Vincenzo: No conflict of interest Quadarella, Alessandro: No conflict of interest Balestrieri, Paola: No conflict of interest Bodini, Giorgia: No conflict of interest Todeschini, Alessia: No conflict of interest Onali, Sara: No conflict of interest Ribaldone, Davide Giuseppe: No conflict of interest Gabrieletto, Enrico Maria: No conflict of interest Mazzuoli, Silvia: No conflict of interest Principi, Maria Beatrice: No conflict of interest Grossi, Laurino: No conflict of interest Daperno, Marco: No conflict of interest