Abstract
OBJECTIVE: Upadacitinib is the first Janus kinase inhibitor and oral advanced therapy licensed for Crohn's disease (CD). Following NICE approval in 2023, real-world data on outcomes are limited. The effectiveness and safety of upadacitinib in a cohort of patients with CD was assessed. METHODS: A multicentre retrospective cohort analysis across 19 UK hospitals. Adult patients with active CD who started upadacitinib between April 2023 and October 2023 were included. Outcomes were reviewed over 24 weeks. The primary endpoint was clinical remission (Harvey Bradshaw Index (HBI) <4) at 12 and 24 weeks. Biochemical remission (faecal calprotectin <200 μg/g and C-reactive protein ≤5) and endoscopic remission (Simple Endoscopic Score for Crohn's Disease ≤3) were assessed at the same intervals. Adverse events (AEs) were recorded until 24 weeks or drug withdrawal. RESULTS: 312 patients were included, with a minimum follow-up of 12 weeks. The cohort had difficult-to-treat disease; 64% failing 3 or more biologics, 51% exhibiting penetrating or stricturing disease and 41% requiring prior resection. 50% (113/227) of patients achieved clinical remission at 12 weeks and 45% (77/172) at 24 weeks. Patients with colonic disease had higher remission rates at 24 weeks compared with other disease locations. At 24 weeks, 51 patients (16%) had discontinued upadacitinib. Treatment persistence was 90.3% at 12 weeks and 84.1% at 24 weeks. 28% had AEs, with 18% experiencing serious AEs and 16.6% requiring hospitalisation. CONCLUSION: This is a large real-world study reporting outcomes in patients with CD treated with upadacitinib. Our data demonstrated good short-term effectiveness and tolerance in a clinically refractory population.