P0890 Real-World Outcomes of Upadacitinib in Crohn’s Disease: Insights from ENEIDA database
Authors: Iborra M , Botella B , Martín-Arranz M D , Ceballos D , Martínez-Pascual C , Ripoll P , Varela P , Moreta M , Montserrat A , González-Lama Y , Rodríguez-González E , Vicuña M , Gisbert J P , Ordás I , Argüelles-Arias F , Tosca J , Vicente R , Sierra M , Rodríguez-Lago I , Martín-Rodríguez D , Paredes J M , Sicilia B , García de la Filia I , Jiménez N , Barreiro de Acosta M , Betoré E , Ferrer I , García-Allés L , Huguet J M , Castellet S , García M J , Gutiérrez A , Ponferrada Á , Ramos L , Calafat M , Domènech E , Nos P 
Published: January 2025

Abstract

Background
Upadacitinib (UPA) is the first oral JAK inhibitor approved for the treatment of Crohn's disease (CD). While its effectiveness and safety are well-documented in pivotal clinical trials, real-world data remain limited. Aim: To evaluate the real-world efficacy and safety of UPA in both the short and long term for CD patients.

Methods
A multicentre, prospective, observational study was conducted on patients receiving UPA since its approval. Epidemiological, clinical and disease-related variables, cardiovascular risk factors (CVRF) and prior treatments, were collected. Disease activity was assessed using the Harvey-Bradshaw Index (HBI), endoscopic/radiological (E/R) evaluations, C-reactive protein (CRP), and faecal calprotectin (FC) levels at baseline, 12, 24, and 52 weeks (W). Adverse events (AEs) hospitalisations, and treatment discontinuations were also recorded.

Results
A total of 300 CD patients were included (mean follow-up of 42 W (SD 27.4)). Of these, 26 (9%) received UPA in combination with biological therapy, 24 (8%) were treated for extraintestinal manifestations (EIM) without luminal disease, and 250 (83%) for luminal CD. Baseline characteristics are presented in Figure 1.
Regarding prior advanced therapies, 15% had received one, 26% two, 29% three and 29% ≥four. At baseline, 70% of patients (210) underwent E/R evaluations, which revealed moderate or severe disease activity in 45% and 37%, respectively. Clinical remission was achieved in 62%, 65% and 67% of patients at W12, 24, 52. FC and CRP levels returned to normal (&lt;250 μg/g and &lt;3 mg/L respectively) in the 50%, 55% and 62%, and 60%, 64% and 65% of the patients at W12, 24 and 52, respectively. Over the follow-up period, HBI, FC, and CRP levels significantly improved (Figure 2) and 113 patients (40%) underwent E/R evaluations of which 16% and 32% showed inactive or mild disease activity, respectively. Patients receiving combination therapy showed significant improvement in HBI though decreases in CRP and FC were not statistically significant. Among those treated for EIM, HBI and FC levels remained normal, while CRP showed a significant reduction. AEs occurred in 68 patients (23%), including 29 discontinuations (43%) without associated mortality. Hospitalisation occurred in 58 patients (19%), and surgery in 26 (9%). Treatment discontinuation occurred in 90 patients (30%) within 52 W due to primary non-response in 51%, loss of response in 13%, AEs in 32%, and other reasons in 4%.

Conclusion
This study highlights the real-world efficacy and safety profile of UPA in CD, particularly in patients with aggressive disease or EIM. Further research is warranted to optimise treatment strategies and outcomes in more heavily pre-treated populations.