Dual therapy with tofacitinib and steroids for acute severe ulcerative colitis: a randomized double-blind placebo-controlled trial
Umang Arora, Mahak Verma, Divya Madan, Mukesh Singh, Devasenathipathy Kandasamy, Himanshu Narang, Manjeet Goyal, Mridul Mahajan, Sandeep K Mundhra, Shubham Prasad, Malambo Mubunnu, Ankur Goyal, Rajesh Panwar, Tushar Sehgal, Nihar Ranjan Dash, Raju Sharma, Vaishali Bhardwaj, Saurabh Kedia, Govind Makharia, Vineet AhujaAbstract
Background
One-third of patients with acute severe ulcerative colitis (ASUC) fail intravenous corticosteroids. We evaluated whether adding tofacitinib to corticosteroids reduces treatment failure in ASUC.
Methods
In this single-center, double-blind, placebo-controlled trial, adults with ASUC were randomized 1:1 to tofacitinib (10 mg three times daily for 3 days, then twice daily) or placebo for 5 days alongside corticosteroids. Primary outcome was treatment failure at day 6 (<3-point Lichtiger reduction or total score ≥10, or colectomy). Secondary outcomes were relapse (≥3-point rise with total ≥10), rescue therapy, and colectomy at 90 days. Modified intention-to-treat analysis was performed. (CTRI/2022/11/047186)
Results
Of 62 randomized patients, 58 were analyzed: 33 in the tofacitinib arm and 25 in the placebo arm. The trial was terminated early because of slow recruitment and did not reach the planned sample size of 98. Day 6 treatment failure was numerically lower with tofacitinib in unadjusted analysis (24.2% vs 36.0%; RR 0.67, 95% CI 0.30-1.51; P = .33) and significantly lower after adjustment for baseline covariate imbalance (adjusted RR 0.47, 95% CI 0.24-0.93; P = .03). At 90 days, colectomy rates were similar (12.1% vs 12.0%; P = 1.0), but more tofacitinib-treated patients remained on assigned therapy (84.4% vs 54.2%) and rescue therapy was lower (HR 0.27, 95% CI 0.09-0.78; P = .01). Serious adverse events occurred in one versus three patients. No deaths occurred with tofacitinib versus two deaths with placebo.
Conclusion
Dual therapy with tofacitinib and steroids in ASUC did not significantly reduce treatment failure at day 6, unless adjustment for baseline imbalance in serum albumin was taken into account. It reduced the need for rescue therapy over 90 days without affecting colectomy risk. Larger clinical trials are required to confirm these findings.