Systematic review: the use of tacrolimus in steroid-refractory ulcerative colitis

Abstract

BACKGROUND: Steroid-refractory ulcerative colitis (SR-UC) is a severe form of ulcerative colitis (UC) that persists despite high-dose corticosteroid therapy. Management is challenging and often requires biologics, immunosuppressants or colectomy. Tacrolimus, a calcineurin inhibitor with immunomodulatory effects, has emerged as a potential alternative, though its efficacy, safety and long-term outcomes remain uncertain. OBJECTIVES: This systematic review evaluates the efficacy and safety of tacrolimus in SR-UC, compares it with anti-tumour necrosis factor (TNF) agents, and examines its role in patients with steroid-refractory ulcerative proctitis (SR-UP). DESIGN: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed using the Oxford Centre for Evidence-Based Medicine framework. DATA SOURCES AND METHODS: A comprehensive search of PubMed and Medline (1998-2025) identified studies reporting clinical remission, response rates, adverse effects and colectomy rates. Subgroup analyses compared oral tacrolimus with anti-TNF therapy and evaluated topical tacrolimus in SR-UP. RESULTS: Seventeen studies (658 patients) met the inclusion criteria. Tacrolimus demonstrated variable efficacy, with clinical remission rates of 9.4%-75.6% and response rates of 28.6%-89.6%. Adverse events, mainly neurotoxicity and nephrotoxicity, occurred in 16.7%-53.0% of cases, sometimes leading to treatment discontinuation. Colectomy rates ranged from 6.1% to 62%. No significant difference was observed between tacrolimus and anti-TNF agents in remission induction, though anti-TNFs had superior long-term outcomes. Topical tacrolimus showed promising efficacy in SR-UP (73.0%-75.0% remission) but was associated with high adverse event rates (45.0%-67.0%). CONCLUSION: Tacrolimus is a viable option for SR-UC, particularly in combination therapy, but its long-term efficacy remains uncertain. While it is comparable to anti-TNFs for short-term remission, high colectomy rates and adverse effects require careful monitoring. Topical tacrolimus shows promise for SR-UP but requires standardised dosing. Further large-scale trials are needed to optimise treatment strategies and evaluate long-term safety. TRIAL REGISTRATION: The review has been registered with PROSPERO (CRD42023432827), the international prospective register of systematic reviews.