Janus Kinase Inhibitors for Acute Severe Ulcerative Colitis: Comparing Upadacitinib to Tofacitinib and Rescue to Sequential Salvage therapy.

BACKGROUND: Acute Severe Ulcerative Colitis (ASUC) remains a medical emergency with limited therapeutic options. Upadacitinib and tofacitinib are Janus kinase (JAK) inhibitors being increasingly used as rescue therapy for ASUC with limited data. We evaluated outcomes of JAK inhibitor use for ASUC over 52 weeks. METHODS: We undertook a multicentre retrospective cohort study across 13 Australian IBD centres. Adults with ASUC who commenced upadacitinib or tofacitinib from April 2021 to April 2024 were included. Outcomes were assessed during index admission, at week 8, 16, and 52. Comparisons of upadacitinib vs tofacitinib and rescue vs sequential salvage therapy were undertaken. The primary outcome for both analyses was colectomy by week 52. RESULTS: 150 patients were included with complete follow-up to 52 weeks. Upadacitinib was used in 51%, tofacitinib in 49%; JAK inhibitors as rescue therapy in 69% and sequential salvage therapy in 31%. Colectomy occurred in 33% of patients by week 52, and was significantly lower with upadacitinib than tofacitinib (23.4% vs 42.5%, weighted marginal risk difference -0.18, p=0.022), with no significance at earlier timepoints. Sequential salvage therapy resulted in a numerically higher rate of colectomy compared to Rescue therapy (38% vs 30%, adjusted marginal risk difference -0.1, p=0.239), but did not meet statistical significance. CONCLUSION: JAK inhibitors were effective for ASUC with a reassuring safety profile. Upadacitinib use resulted in a significantly lower rate of colectomy by week 52, with higher rates of clinical remission, CFCR, and biochemical remission during follow-up. Sequential salvage therapy may represent a viable therapeutic option for patients otherwise facing colectomy.