Upadacitinib Maintenance Therapy in Crohn’s Disease: Final Results From the Randomized Phase 3 U-ENDURE Study

BACKGROUND & AIMS: Upadacitinib, an oral, reversible Janus kinase inhibitor, demonstrated efficacy and safety in patients with Crohn's disease in 2 phase III induction trials (U-EXCEL and U-EXCEED) and in a primary analysis of the first 502 patients entering the subsequent maintenance trial (U-ENDURE). Here, we present the overall results of the entire population of U-ENDURE (N = 673). METHODS: Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks. Coprimary endpoints were Crohn's Disease Activity Index (CDAI) clinical remission and endoscopic response at week 52. Safety was assessed through week 52. RESULTS: At week 52, more upadacitinib-treated vs placebo patients achieved CDAI clinical remission (upadacitinib 15 mg, 36.2% and upadacitinib 30 mg, 51.5% vs placebo, 15.2%). The rates of endoscopic response were 27.3% for upadacitinib 15 mg and 40.7% for upadacitinib 30 mg vs 7.2% for placebo. Exposure-adjusted event rates for treatment-emergent adverse events were numerically lower with upadacitinib 15 mg and 30 mg vs placebo (351.3 and 324.5 per 100 patient-years, respectively, vs 462.8 per 100 patient-years) except for COVID-19 and adverse events leading to early discontinuation of study treatment. No deaths, active tuberculosis, lymphoma, nonmelanoma skin cancer, adjudicated major cardiovascular adverse events, or venous thromboembolic events were reported from any treatment group. Herpes zoster infections occurred more frequently in the upadacitinib groups compared with placebo; all were nonserious, and most involved a single dermatome. CONCLUSIONS: Consistent with the primary analysis, upadacitinib was more efficacious than placebo in achieving clinical and endoscopic endpoints in patients with Crohn's disease. The safety profile remained consistent with no new safety signals. CLINICALTRIALS: gov Number: NCT03345823.