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

Background: 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).

Methods: 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).

Results: 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%.

Conclusion: 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.