Real-world comparison of the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis: the TORUS study.

Background And Aims: We compared the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent.

Methods: In this multicenter real-world evidence study, we consecutively included UC patients ≥18 years-old, previously exposed to anti-TNF therapy, with partial Mayo score >2 and, starting tofacitinib or ustekinumab. All the comparisons were performed using propensity score analyses.

Results: Overall, 124 and 165 patients were included in tofacitinib and ustekinumab groups, respectively. Symptomatic remission, off corticosteroids (CFREM=partial Mayo score ≤2) was achieved at week16 in 37.8% and 35.8%, among tofacitinib and ustekinumab groups, respectively (aOR=1.09 [0.60-2.00]; p=0.75), with higher tofacitinib effectiveness in patients with prior exposure to≥ 3 biologics (46.7% vs 23.1%; aOR=2.92[1.02-8.39], p=0.047). Primary failure to any biologic (OR=2.88[1.20 -6.98]) and prior exposure to≥ 3 advanced therapies (OR=2.45[1.03-5.82]), but not disease severity, were associated with ustekinumab failure. We did not find any significant difference between tofacitinib and ustekinumab regarding clinical remission per modified Mayo score (17.0% vs 11.7%; aOR=1.55[0.65-3.68]; p=0.32) and histological and endoscopic improvement (HEMI) (4.4% vs 7.8%; aOR=0.54[0.16-1.86], p=0.32). After a median follow-up of 11.8 months [6.1-20.5]), we did not observe any difference regarding the risk of UC relapse-related drug discontinuation (aHR=1.44[0.94-2.21], p=0.10), and the risk of secondary loss of response among patients achieving CFREM at week 16 (aHR=1.88 [0.57-6.19], p=0.30).

Conclusion: Tofacitinib and ustekinumab are similarly effective to induce and maintain CFREM after anti-TNF failure in UC. However, tofacitinib could be favored in case of multiple therapeutic failures (≥ 3 biologics) and primary failure to any biologic.