JAK Inhibitors in Ulcerative Colitis

Comparative Efficacy and Safety

The American Gastroenterological Association includes both tofacitinib and upadacitinib in their 2024 network meta-analysis, with tofacitinib showing a relative risk of 10.45 (95% CI 2.09-52.22) for clinical remission versus placebo, and a P-score of 0.87, in biologic-exposed patients 4, 5
Upadacitinib demonstrated superior efficacy with a relative risk of 14.05 (95% CI 4.94-43.94) and P-score of 0.93, though based on fewer patient-years of data 4, 5
Upadacitinib's UC program consists of two induction studies and one maintenance study, with 474 patients in the U-ACHIEVE induction trial, and clinical remission rates of 33% and 26% with placebo rates of only 4% and 5% 1, 2
The OCTAVE program included 53-58% of patients with prior anti-TNF exposure, providing extensive data in biologic-experienced populations 3
Upadacitinib trials included 30-35% of patients with prior exposure to 2 biologics, representing a more treatment-refractory population 4

Comprehensive safety data from rheumatoid arthritis populations informed UC prescribing, including the ORAL Surveillance study that identified cardiovascular and malignancy risks 1, 5
Post-hoc analyses of tofacitinib UC trials and observational studies did not identify clear increases in venous thromboembolism or major adverse cardiovascular events in UC populations 2, 5
Multiple real-world cohort studies have compared tofacitinib to vedolizumab and other biologics in UC, including propensity-matched analyses and registry-based studies 6, 7

Safety concerns from the JAK inhibitor class apply to upadacitinib, but UC-specific long-term safety data remains more limited compared to tofacitinib 2, 4
The FDA boxed warning requiring prior TNF antagonist failure applies to all JAK inhibitors, informed primarily by tofacitinib rheumatoid arthritis data 2, 4