Tofacitinib and Ustekinumab Show Comparable Efficacy After Anti-TNF Failure in Ulcerative Colitis

A multicenter real-world study comparing tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to anti-TNF therapy found that both agents are similarly effective in achieving corticosteroid-free remission. However, tofacitinib may offer an advantage in patients with multiple prior treatment failures.

The study included 289 patients (124 tofacitinib, 165 ustekinumab) with a partial Mayo score >2 at baseline. At week 16, corticosteroid-free symptomatic remission (partial Mayo score ≤2) was achieved in 37.8% of tofacitinib users and 35.8% of ustekinumab users (adjusted OR, 1.09; P = .75).

No significant differences were observed in clinical remission (17.0% vs 11.7%) or histologic and endoscopic improvement (4.4% vs 7.8%), nor in rates of drug discontinuation or secondary loss of response during a median follow-up of 11.8 months.

However, tofacitinib was significantly more effective than ustekinumab among patients with prior exposure to three or more biologics (46.7% vs 23.1%; adjusted OR, 2.92; P = .047). Additionally, primary failure to any biologic (OR, 2.88) and exposure to ≥3 advanced therapies (OR, 2.45) were predictors of ustekinumab failure, independent of baseline disease severity.

“Tofacitinib and ustekinumab are similarly effective to induce and maintain corticosteroid-free remission after anti-TNF failure in UC,” the authors reported. “However, tofacitinib could be favored in case of multiple therapeutic failures (≥3 biologics) and primary failure to any biologic.”

For gastroenterologists managing treatment-refractory UC, these findings support individualized treatment selection based on prior biologic response, with tofacitinib offering potential benefit in highly treatment-experienced patients.

Reference
Buisson A, Serrero M, Altwegg R, et al. Real-world comparison of the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis: the TORUS study. Clin Gastroenterol Hepatol. Published online August 18, 2025. doi:10.1016/j.cgh.2025.07.044