Real-world Effectiveness and Safety of Tofacitinib in Multi-Refractory Ulcerative Colitis: insights from a Belgian Cohort with prior Anti-TNF and Vedolizumab Exposure

Abstract

Background and aims: Tofacitinib has expanded treatment options for moderate-to-severe ulcerative colitis (UC). Longterm real-world data on its efficacy and safety remain limited, particularly in multi-refractory populations. This study evaluated the real-world effectiveness and safety of tofacitinib in Belgian UC patients with prior exposure to anti-TNF and vedolizumab. Patients and methods: This retrospective multicentric observational study included consecutive adult UC patients from 26 Belgian centers who initiated tofacitinib through an early access program (November 2018-August 2019). Data were prospectively collected. Primary endpoint was clinical remission (partial adapted Mayo score <= 1) at the end of follow-up (predefined as week 52). Secondary endpoints included endoscopic outcomes, treatment retention rate, colectomy-free survival, and adverse events (AEs). Results: Seventy-five patients (59% men, median age 44 years) were included, with a median treatment duration of 45 weeks (IQR:19-51). At baseline, 96% had prior anti-TNF and 97% antiintegrin exposure, while 56% were on concomitant steroids. Clinical remission was achieved by 43% at the end of follow-up. Endoscopic response and remission were observed in 37% and 9% of patients, respectively. Fecal calprotectin <250<mu>g/g at week 16 predicted clinical remission at the end of follow-up (OR:0.03, p=0.01). Overall, 34 patients (45%) discontinued tofacitinib, primarily due to primary non-response (62%). AEs were reported in 33% of patients, with the most common being arthralgia, respiratory tract infections, and herpes zoster. No major cardiovascular events or opportunistic infections occurred. Conclusion: In a real-world Belgian cohort of multi-refractory UC patients, tofacitinib demonstrated effectiveness in achieving clinical remission by the end of follow-up with no new safety signals identified. These findings support its use in this challenging patient population. (Acta gastroenterol belg., 2025, 88, 229-237).