Abstract Background We previously reported that upadacitinib (UPA) demonstrated higher effectiveness than filgotinib (FIL) in the treatment of ulcerative colitis (UC) [1]. We aimed to compare safety profiles between FIL and UPA. Methods A multicenter, retrospective observational study was conducted in patients with UC over 18 years old who received FIL or UPA from March 2022 to December 2023 at three territory specialist centres in Japan. The adverse events (AEs) observed in each treatment group were reviewed in detail, and the incidence of AEs was compared using 1:1 propensity score matching (PSM), adjusting for gender, age, disease duration, disease extent, severity (partial Mayo score), previous exposure to biologics or tofacitinib, concomitant medications (5-aminosalicylic acid, immunomodulators, corticosteroids), laboratory data (CRP, Hb, Alb), past medical history, and smoking status. Results A total of 197 patients were enrolled, including 120 patients treated with FIL (median treatment duration 191 days) and 77 with UPA (median treatment duration 154 days). The incidence of AEs was 25.0% (30/120) in the FIL group and 45.5% (35/77) in the UPA group (p<0.01) (Table). The proportion of AEs that resulted in drug discontinuation was 5.0% (6/120) in the FIL groups and 18.2% (14/77) in the UPA group (p<0.01). Only five patients developed herpes zoster (FIL: 3, UPA: 2). No major adverse cardiovascular events, thrombosis or malignancy due to the medication were observed during the study period. At the time of AEs identified, 77.1% of the administered UPA doses were 45 mg. In the PSM approach, a cohort of 55 patients in each group was obtained. After PSM (n=55 each) , the incidence of AEs was 14.6% in the FIL group and 43.6% in the UPA group (risk differnce 29.1, 95% confidence interval [CI]: 13.0-45.2, risk ratio 3.00, 95%CI: 1.48-6.09), which was significantly higher in the UPA group than the FIL group. Conclusion The higher incidence of AEs observed in this study needs to be taken into account when prescribing UPA although it has relatively high efficacy in UC patients.
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