Comparing real-world continuous clinical remission rates of anti-tumor necrosis factor, vedolizumab, ustekinumab, tofacitinib, and upadacitinib in ulcerative colitis

Background Multiple advanced therapies are available for moderate-to-severe ulcerative colitis (UC), but comparative efficacy data are limited. We compared the 1-year efficacy and safety of 7 therapies: the anti-tumor necrosis factor agents infliximab, adalimumab, and golimumab (GLM); the anti-integrin vedolizumab (VDZ); the anti-interleukin-12/23 ustekinumab (UST); and the JAK inhibitors tofacitinib (TOF) and upadacitinib (UPA). Methods In a retrospective, multicenter, propensity score–matched study, all UC patients treated with the 7 advanced therapies between 2014 and 2024 were included. The primary endpoint was the 1-year rate of continuous clinical remission (CCR) for each drug (defined as the induction and maintenance of steroid-free clinical remission, without the need for drug optimization or additional therapy due to relapse, with no adverse events requiring drug discontinuation). Results A total of 1406 patients were included (VDZ = 376, infliximab = 341, adalimumab = 207, UST = 150, GLM = 114, TOF = 103, UPA = 115). Excluding UPA from the overall population comparison as it was used only in bio-exposed patients, UST achieved the highest CCR, with GLM the lowest. UST appeared the most effective therapy in bio-naive patients, whereas other biologics achieved similar CCR rates. As second-line therapy, UPA achieved the highest CCR, followed by UST. As third-line therapy, UPA outperformed UST, VDZ, and TOF. UST was associated with the lowest rates of adverse events. Although UPA was associated with the highest rates of adverse events, drug withdrawal was low. Conclusions In this large multicenter observational cohort, UST was more effective than anti-tumor necrosis factor agents and VDZ as both first- and second-line therapy. In bio-exposed patients, UPA was the most effective advanced therapy.