A multicentered retrospective cohort study comparing JAK inhibitor therapies in moderate-to-severe ulcerative colitis.

Abstract

Background: Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKi) that have demonstrated efficacy in ulcerative colitis (UC) against placebo. This study aims to compare the clinical efficacy between these drugs.

Methods: This is a multicentered, retrospective cohort study. Patients with UC starting a JAKi were recruited between 2018 and 2024 when starting their first JAKi. Clinical remission and response, based on clinical scores, calprotectin, and endoscopic measurement, were assessed at 3 and 6 months. Both independent and combined variable outcomes were analyzed.

Results: Two hundred and seventy patients were included in the analysis, of which 70 (26%) were on upadacitinib, 51 (19%) on filgotinib, and 149 (55%) on tofacitinib. Clinical, biochemical, and endoscopic remission at 6 months was 91%, 71%, and 80% for upadacitinib; 78%, 67%, and 50% for filgotinib; 73%, 51%, and 44% for tofacitinib. Upadacitinib demonstrated significantly greater clinical response (P = .027) and remission (P = .037) rates at 6 months than tofacitinib. Drug persistence at 12 months was 86% for upadacitinib, 72% for filgotinib, and 69% for tofacitinib. Upadacitinib demonstrated significantly greater 6-month remission rates compared to tofacitinib in the bio-exposed cohort (71% vs 52%, P = .022) and in the bio-naïve cohort (93% vs 50%, P = .009). The incidence rates for hospital admissions were 10.2, 21.9, and 14.1 and for colectomies were 6.7, 10.0, and 5.0 per 1000 patient-months at risk for upadacitinib, filgotinib and tofacitinib, respectively.

Conclusion: This study demonstrates that upadacitinib is more likely to achieve 6-month response and remission compared to tofacitinib. In both bio-naïve and bio-exposed patients, upadacitinib was more likely to achieve remission at 6 months. The efficacy of JAKi does not appear diminished by prior biologic use.