Tofacitinib in acute severe ulcerative colitis: review addressing seven key unmet needs

Tofacitinib, an oral Janus kinase (JAK) inhibitor, shows promise as a rescue therapy for acute severe ulcerative colitis (ASUC), a life-threatening condition marked by high colectomy rates. This narrative review synthesizes evidence from randomized controlled trials (RCTs), observational studies, and systematic reviews. The efficacy of tofacitinib has been documented, with an 83.01% day-7 response rate in the TACOS trial and 79.9%-86% 90-day colectomy-free survival in steroid-refractory ASUC. However, seven unmet needs impede the adoption of tofacitinib treatment for managing ASUC: (1) a lack of head-to-head RCTs comparing tofacitinib not only to standard rescue therapies like infliximab and ciclosporin but also to other JAK inhibitors like upadacitinib, (2) uncertainty in optimal dosing and duration, (3) ambiguity in positioning tofacitinib in the treatment algorithm, (4) undefined patient selection criteria, notably for those with prior biologic exposure, (5) limited long-term efficacy and cost-utilization data, (6) unresolved safety risks (e.g., infections, thrombosis), and (7) underexplored potential for combination therapy. These gaps undermine the widespread use of tofacitinib in reducing surgical burden and improving outcomes. Collaborative research-especially multi-center RCTs comparing tofacitinib to infliximab, ciclosporin, and next-generation JAK inhibitors-is vital for establishing evidence-based protocols. Addressing these needs could optimize tofacitinib-based ASUC management, offering a rapid, oral alternative to enhance patient care.