Real-World Effectiveness and Safety of Upadacitinib in Crohn’s disease: A Multi-Centre Study

We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor (JAKi) in patients with Crohn's disease (CD). A retrospective analysis was conducted across nine centers in the United States, focusing on adults with CD treated with UPA 45 mg as induction therapy for active luminal disease. The co-primary endpoints were clinical remission at 12 weeks (Harvey Bradshaw Index ≤ 4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (SEMA-CD score of 0-1 or absence of ulcers). Secondary outcomes included clinical, radiographic and histologic outcomes, and adverse events (AEs). The study included 334 CD patients (median age 34 years and disease duration 12 years, and 44.6% female). Clinical remission was achieved in 52.1% at 12 weeks and 55.9% at 6 months. Endoscopic remission at 6 months was observed in 42.7% of patients. Advanced therapy (AT)-naive patients achieved a higher proportion of clinical remission at 12 weeks (58.6%) and 6 months (97.7%) compared to patients with one prior AT (53.3% and 66.7%) and two or more prior AT exposures (50.2% and 40.5%), respectively. BMI and longer disease duration was associated with lower odds of clinical remission at 12 weeks. AEs were reported in 13.5% and UPA discontinued in 19.1%. UPA was effective at inducing clinical and endoscopic remission in a real-world group of patients with CD, even with prior exposure to multiple prior advanced therapies. No new safety concerns were identified.