Tacrolimus Bridging and Combination Therapy Following Infliximab and JAK Inhibitor Failure in Ulcerative Colitis: A Case Series.

BACKGROUND: Calcineurin inhibitors such as tacrolimus are established rescue therapies for steroid-refractory ulcerative colitis (UC). However, their efficacy and safety as bridging or combination therapy following failure of both anti-tumor necrosis factor (anti-TNF) and Janus kinase (JAK) inhibitor therapy remain uncertain. METHODS: We conducted a retrospective, single-center case series at a tertiary referral center between January 2020 and December 2025. Adult patients with treatment-refractory UC who received tacrolimus after documented failure of infliximab and a JAK inhibitor were included. Demographic, disease, treatment, and outcome data were collected. RESULTS: Seven patients were included (median age, 37.1 years; median disease duration, 6 years), of whom three presented with acute severe UC. Tacrolimus was used as bridging therapy to ustekinumab (n = 4), ozanimod (n = 1), or upadacitinib (n = 1), and as combination therapy with upadacitinib (n = 1). Median tacrolimus treatment duration was 3 months, and median follow-up was 31 months. Six of seven patients achieved a clinical response, including four who achieved clinical remission. Three patients ultimately required colectomy. No serious adverse events were observed; one patient developed tremor and one experienced mild COVID-19 infection. CONCLUSION: Tacrolimus may be a useful bridging or combination therapy in carefully selected patients with UC refractory to both infliximab and JAK inhibitors. Nevertheless, the substantial colectomy rate underscores the severity of disease in this population and highlights the importance of close monitoring and shared decision-making. Larger prospective studies are needed to better define the optimal role, duration, and safety of tacrolimus in this treatment setting.