Real-World Comparative Effectiveness and Safety of Filgotinib and Upadacitinib for Ulcerative Colitis: A Multicentre Cohort Study.

Background: Janus kinase (JAK) inhibitors, filgotinib (FIL) and upadacitinib (UPA) have emerged as promising treatments for ulcerative colitis (UC). However, a comparative analysis of these JAK inhibitors, particularly in patients previously treated with tofacitinib (TOF), has not been performed.

Aims: To compare the efficacy and safety of FIL and UPA in patients with UC, including those previously exposed to TOF.

Methods: A multicentre retrospective cohort study was conducted to compare the effectiveness and safety of FIL and UPA in patients with UC whose treatment was initiated between March 2022 and December 2023. The co-primary outcomes were clinical response and remission at week 8. The secondary outcomes included treatment persistence and adverse events (AEs). Modified Poisson and Cox regression models with multivariable analysis to adjust for confounders and propensity score matching were conducted. Subgroup analyses stratified by previous exposure to TOF and biologics were also conducted.

Results: In total, 168 patients (98 treated with FIL and 70 treated with UPA) were enrolled in this study, with a median follow-up period of 181 days. The clinical response/remission rates at week 8 were 55.1/46.9% for FIL and 71.4/65.7% for UPA, respectively. UPA was associated with significantly higher rates of clinical response (adjusted risk ratio [RR] 1.40 [95% confidence interval [CI], 1.09 to 1.80]) and clinical remission (adjusted RR 1.54 [95% CI, 1.16 to 2.05]) compared with FIL. This result was consistent across subgroup analyses based on previous exposure to TOF or biologics, except for bio-naive patients. There was no significant difference in the treatment persistence. AEs were more frequent with UPA (45.7%) than with FIL (24.5%) (p = 0.0049). Propensity score matching confirmed the superior overall effectiveness of UPA.

Conclusions: UPA demonstrated better short-term effectiveness than FIL, with a higher incidence of AEs.