Real-world Comparison of the Effectiveness of Tofacitinib and Ustekinumab in Patients With Ulcerative Colitis: The TORUS Study

Abstract

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

Methods: In this multicenter real-world evidence study, we consecutively included patients with UC ≥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 the tofacitinib and ustekinumab groups, respectively. Symptomatic remission, off corticosteroids (partial Mayo score ≤2) was achieved at week 16 in 37.8% and 35.8%, among the tofacitinib and ustekinumab groups, respectively (adjusted odds ratio [OR], 1.09; 95% confidence interval [CI], 0.60-2.00; P = .75), with higher tofacitinib effectiveness in patients with prior exposure to ≥3 biologics (46.7% vs 23.1%; adjusted OR, 2.92; 95% CI, 1.02-8.39; P = .047). Primary failure to any biologic (OR, 2.88; 95% CI, 1.20-6.98) and prior exposure to ≥3 advanced therapies (OR, 2.45; 95% CI, 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%; adjusted OR, 1.55; 95% CI, 0.65-3.68; P = .32) and histological and endoscopic improvement (4.4% vs 7.8%; adjusted OR, 0.54; 95% CI, 0.16-1.86; P = .32). After a median follow-up of 11.8 months (interquartile range, 6.1-20.5 months), we did not observe any difference regarding the risk of UC relapse-related drug discontinuation (adjusted hazard ratio, 1.44; 95% CI, 0.94-2.21; P = .10), and the risk of secondary loss of response among patients achieving CFREM at week 16 (adjusted hazard ratio, 1.88; 95% CI, 0.57-6.19; P = .30).

Conclusion: Tofacitinib and ustekinumab are similarly effective to induce and maintain corticosteroid-free remission 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.

Keywords: Inflammatory Bowel Disease; JAK Inhibitors; Tofacitinib; Ulcerative Colitis; Ustekinumab.