Abstract Background One-third of patients with acute severe ulcerative colitis (ASUC) fail to improve with intravenous steroids, necessitating early adjunctive therapy. Tofacitinib, a rapid-acting JAK inhibitor, is effective in severe UC, but prospective data in ASUC is limited. This trial evaluated whether adding tofacitinib to standard therapy improves clinical response and avoid colectomy Methods In this single-center, investigaor-led, placebo-controlled trial (TOFA-ASUC), consecutive adults with ASUC (defined by Truelove–Witts criteria) received standard-of-care intravenous corticosteroids and were randomized in a double-blind 1:1 allocation to tofacitinib (10 mg thrice daily for 3 days, then twice daily) or placebo for 5 days. Primary outcome was assessed at completion of 5 days, defined as a ≥ 3-point reduction in Lichtiger score and total ≤10. Secondary outcomes included clinical relapse (≥3-point rise in Lichtiger score with total ≥10), need for rescue therapy, colectomy, and mortality over 3 months. Registered at CTRI/2022/11/047186 Results From 02/2023-02/2025, 73 individuals were screened and 62 were randomized; 4 excluded for predefined reasons, leaving 58 participants in the modified intention-to-treat cohort (33 assigned to tofacitinib and 25 to placebo). After 5 days, clinical response occurred in 25/33(75.8%) receiving tofacitinib and 16/25(64%) receiving placebo (p = 0.39). Relapse among responders (16% vs 18.8%, p = 1.00), colectomy (12.1% vs 12%, p = 1.00), mortality (0/33 vs 2/25, p = 0.18), and median hospital stay (13 8–16 vs 12 7–18 days, p = 0.50) were similar. Of 8 non-responders in the tofacitinib group, 4 improved subsequently without additional rescue, while 3 received infliximab (2 later required colectomy); 2 early responders relapsed and required colectomy. In placebo group (n = 25), 9 failed to respond and 3 relapsed, 8 of whom received tofacitinib as rescue, with 6 responding completely while 1 each required infliximab and colectomy. Overall, 27/33 (81.8%) in the tofacitinib arm and 13/25(52%) in the placebo arm achieved colectomy-free survival at 3 months with their initial strategy (log-rank p = 0.01). Major infections occurred in 1 (3.1%) patient in the tofacitinib arm (tubercular meningitis) and 3/24 (12.5%) in the placebo arm (CMV colitis, postoperative sepsis, and refractory shock) while minor infections were similar in both groups, with no episodes of venous thromboembolism or herpes zoster. Conclusion In this prospective RCT, addition of up-front tofacitinib to intravenous corticosteroids in ASUC yielded numerically higher but non-significant early clinical responses, with similar relapse, colectomy, or mortality rates. Colectomy-free survival without additional rescue therapy was significantly higher with dual therapy. Conflict of interest: Arora, Umang: The submitted abstract is from an investigator-initiated and investigator-led study, which was funded by IPCA Laboratories, India, in the form of study medication (tofacitinib and corresponding placebo). The IPCA team was updated periodically about adverse events in either arm, but was not involved in clinical monitoring or analysis. Verma, Mahak: None Madan, Divya: No conflict of interest Kumar, Mukesh: I don’t have conflict of interest. Kandasamy, Devasenathipathy: No conflict of interest Narang, Himanshu: No conflict of interest Goyal, Manjeet: No conflict of interest Mubbunu, Malambo: No conflict of interest Mahajan, Mridul: No conflict of interest Panwar, Rajesh: No conflict of interest Dash, Nihar Ranjan: No conflict of interest Goyal, Ankur: No conflict of interest Sharma, Raju: No conflict of interest Kedia, Saurabh: No conflict of interest Makharia, Govind K: No conflict of interest Ahuja, Vineet: No conflict of interest
Arora et al. (Thu,) studied this question.