Tofacitinib as Rescue Therapy in Steroid-Refractory Acute Severe Ulcerative Colitis: A Retrospective Cohort Study...

Acute severe ulcerative colitis (ASUC) is a severe and potentially life-threatening condition in which one-third of patients are refractory to intravenous corticosteroids. Established rescue therapies--infliximab and cyclosporine--are limited by cost, administration constraints, and toxicity. Tofacitinib, an oral Janus kinase (JAK) inhibitor, possesses pharmacokinetic and mechanistic properties that may be advantageous in the inpatient setting. This study was conducted to assess the short-term efficacy and safety of tofacitinib as rescue therapy in steroid-refractory ASUC and to identify clinical predictors of treatment failure.

We conducted a retrospective cohort analysis of all patients with ASUC admitted to our tertiary gastroenterology unit between March 2023 and August 2025. ASUC was defined per Truelove and Witts' criteria. Patients who failed to respond to intravenous hydrocortisone by Day 3 and who could not receive infliximab (due to cost or contraindication) were initiated on tofacitinib (10 mg thrice daily for 3 days, followed by 10 mg twice daily). The primary outcome was clinical response by Day 5-7, defined as a reduction in Mayo score of ≥3 points (≥30% from baseline) with an absolute rectal bleeding sub-score of 0-1. Secondary outcomes included non-response rate, adverse events, and the impact of colonic cytomegalovirus (CMV) DNA burden on treatment response.

Ten consecutive patients with steroid-refractory ASUC received tofacitinib rescue therapy. The mean age was 29.6 ± 9.1 years; 60% were male. Seven patients (70%) achieved clinical response within 5-7 days. Three patients (30%) failed to respond and required alternative rescue therapy or surgical consultation. CMV DNA was detected in the colonic tissue of four patients; both patients with high viral loads (>50,000 copies/mL) failed to respond to tofacitinib despite concurrent antiviral therapy. Adverse events were minimal; one patient developed bicytopenia of uncertain attribution.

Tofacitinib demonstrated a 70% short-term clinical response rate in steroid-refractory ASUC, with an acceptable safety profile. Higher colonic CMV DNA appeared to be associated with a lower likelihood of clinical response; however, this observation requires validation with further research. Tofacitinib represents a viable, cost-effective rescue option, particularly in resource-limited settings or when conventional biologics are contraindicated. Prospective comparative studies are needed to define its optimal positioning within ASUC treatment algorithms.