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

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.

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.

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.

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.