Real‐World Effectiveness and Safety of Upadacitinib in Crohn's Disease: Insights From the Eneida Registry
Year: 2026
Type: article
Study design: Observational Study
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.
DOI: 10.1002/ueg2.70223
Authors: M. Iborra, B. Botella, M. D. Martín‐Arranz, D. Ceballos, C. Martínez‐Pascual, A. Garrido, P. Varela, M. Moreta, E. Brunet‐Mas, Y. González‐Lama, E. Rodríguez‐González, M. Vicuña, J. P. Gisbert, I. Ordás, F. Argüelles‐Arias, J. Tosca‐Cuquerella, R. Vicente‐Lidón, M. Sierra‐Ausín, I. Rodríguez‐Lago, D. Martín‐Rodríguez, J. M. Paredes, B. Sicilia, I. García de la Filia, N. Jiménez, M. Barreiro‐de Acosta, E. Betoré, I. Ferrer‐Bradley, L. García‐Alles, J. M. Huguet, S. Castellet‐Farrús, M. J. García, A. Gutiérrez‐Casbas, Á. Ponferrada‐Díaz, L. Ramos, M. Calafat, I. Vera, C. Suárez‐Ferrer, E. Fernández‐Velado, S. Rodríguez‐Sánchez, A. Mínguez, A. Mancebo, J. Barrio, S. Lario, D. R. de La Cruz, Alejandro Hernández‐Camba, C. Rodríguez‐Gutiérrez, M. Chaparro, E. Ricart, L. Almenara‐Michelena, A. Balaguer, E. Domènech, P. Nos
Institutions: Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Hospital Universitario Puerta de Hierro Majadahonda, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, Universidad Autónoma de Madrid, Universidad de Las Palmas de Gran Canaria, Hospital Universitario de Gran Canaria Doctor Negrín, Hospital Universitario Virgen de la Arrixaca, Hospital Universitario De Cabueñes, Hospital Universitario Río Hortega, Universitat Autònoma de Barcelona, Corporació Sanitària Parc Taulí, Institute of Research and Innovation Parc Tauli, Universidad Complutense de Madrid, Hospital Universitario Nuestra Señora de Candelaria, Universidad de Navarra, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Hospital Clínico Universitario de Valencia, Hospital Universitario Miguel Servet, Complejo Asistencial Universitario de León, Hospital de Galdakao, Hospital Universitario Infanta Cristina, Hospital Universitario Doctor Peset, Hospital Universitario de Burgos, Hospital Universitario Ramón y Cajal, Hospital General Universitario de Elche, Complejo Hospitalario Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago, Hospital General San Jorge, Hospital de Manises, Hospital Sierrallana, Hospital General Universitario De Valencia, Bellvitge University Hospital, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital General Universitario de Alicante Doctor Balmis, Hospital Universitario Infanta Leonor, Hospital Universitario de Canarias, Hospital Universitari Germans Trias i Pujol, Instituto Murciano de Investigación Biosanitaria, Gerencia Regional de Salud de Castilla y León (Sacyl), Hospital Universitario 12 De Octubre, Navarre Institute of Health Research
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
OpenAlex ID: W7158467319