Real-World Effectiveness and Safety of Upadacitinib in Crohn's Disease: Insights From the Eneida Registry

Abstract

Background: Upadacitinib (UPA) is the first oral Janus kinase (JAK) inhibitor approved for the treatment of Crohn's disease (CD). Real-world data, particularly from large nationwide cohorts, remain limited. This study aimed to evaluate the real-world effectiveness, safety, and treatment persistence of UPA in patients with CD. Methods: Multicenter observational study including patients with CD who received UPA, using data from a nationwide registry. Patients were classified according to active luminal disease, extraintestinal manifestations (EIMs), or combination therapy with another biological therapy. Disease activity was assessed using the Harvey–Bradshaw Index (HBI), C-reactive protein (CRP), and fecal calprotectin (FC) at baseline and weeks 12, 24, and 52. Endoscopic outcomes were evaluated when available. Adverse events (AEs), hospitalizations, and treatment discontinuations were recorded. Results: 300 patients were included, representing a highly treatment-refractory population, with 98% previously exposed to anti-TNF agents and 59% to three or more advanced therapies. In those treated for active luminal disease, corticosteroid-free clinical remission was achieved in 60%–62% of patients at weeks 12, 24 and 52. CRP normalization increased from 64% at week 12%–74% at week 52, while FC normalization improved from 48% to 64%. Patients treated for EIMs achieved high and sustained remission rates with excellent treatment persistence. Early remission at week 12 was strongly associated with sustained remission and meaningful endoscopic improvement. UPA was discontinued in 98 patients (39%). AEs were reported in 71 patients (24%). Conclusions: In this large real-world cohort, UPA demonstrated sustained clinical and biochemical effectiveness, meaningful endoscopic response, and a safety profile consistent with clinical trial data. Early response emerged as a key predictor of long-term outcomes, supporting the clinical utility of UPA.