Am J Gastroenterol. 2024 Nov 26. doi: 10.14309/ajg.0000000000003243. Online ahead of print.

María José García ¹, Yanire Brenes ², Miren Vicuña ³, Fernando Bermejo ⁴, Mónica Sierra-Ausín ⁵, Raquel Vicente ⁶, María Teresa Arroyo ⁷, Pilar Martínez Montiel ⁸, Albert Villoria ⁹, Juan Ángel Ferrer ¹⁰, Vicent Hernandez ¹¹, Alexis Piñero ¹², Marta Carrillo-Palau ¹³, María Dolores Martín-Arranz ¹⁴, José Miranda-Bautista ¹⁵, Ramón Pajares ¹⁶, Laura Arranz Hernández ¹⁷, Ana Bejarano ¹⁸, Jordi Guardiola ¹⁹, Eduardo Iyo ²⁰, Carmen Muñoz-Villafranca ²¹, Aurora Talavera ²², Horacio Alonso-Galán ²³, Manuel Barreiro-de Acosta ²⁴, Maia Bosca-Watts ²⁵, Teresa Vázquez Rey ²⁶, Ana Echarri ²⁷, María Del Carmen Rodríguez-Grau ²⁸, Ana Gutiérrez ²⁹, José María Huguet ³⁰, M Carmen López-Martín ³¹, Francisco Mesonero ³², Isabel Pérez-Martínez ³³, Rocío Plaza ³⁴, Patricia Ramírez de la Piscina ³⁵, Javier P Gisbert ², María Chaparro ²

Author information

¹Gastroenterology and Hepatology Department Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Sanitaria Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain.

²Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.

³Gastroenterology Department, Complejo Hospitalario de Navarra, Pamplona, Spain.

⁴Gastroenterology Department. Hospital Universitario de Fuenlabrada. Madrid, Spain.

⁵Gastroenterology Department, Complejo Asistencial Universitario de León, León, Spain.

⁶Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.

⁷Gastroenterology Department, Hospital Clínico Universitario "Lozano Blesa", IIS Aragón and CIBERehd, Zaragoza, Spain.

⁸Gastroenterology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

⁹Gastroenterology Department, Consorci Corporació Sanitària Parc Taulí, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Sabadell, Spain.

¹⁰Gastroenterology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.

¹¹Gastroenterology Department, Hospital Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.

¹²Gastroenterology Department, Hospital Universitario de Jerez de la Frontera, Jerez de la Frontera, Spain.

¹³Gastroenterology Department, Hospital Universitario de Canarias, La Laguna, Spain.

¹⁴Gastroenterology Department, Hospital Universitario La Paz, Instituto de Investigación Sanitaria La Paz (IdiPaz), Universidad Autónoma de Madrid, Madrid, Spain.

¹⁵Gastroenterology Department, Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.

¹⁶Gastroenterology Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain.

¹⁷Gastroenterology Department, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain.

¹⁸Gastroenterology Department, Hospital Juan Ramón Jiménez, Huelva, Spain.

¹⁹Gastroenterology Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.

²⁰Gastroenterology Department, Hospital Comarcal de Inca, Inca, Spain.

²¹Gastroenterology Department, Hospital Universitario de Basurto, Bilbao, Spain.

²²Gastroenterology Department, Hospital Infanta Elena, Huelva, Spain.

²³Gastroenterology Department, Hospital Universitario Donostia, Instituto Biogipuzkoa, San Sebastián, Spain.

²⁴Gastroenterology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.

²⁵Gastroenterology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.

²⁶Gastroenterology Department, Hospital Universitario de A Coruña, A Coruña, Spain.

²⁷Gastroenterology Department, Hospital Arquitecto Marcide, Ferrol, La Coruña, Spain.

²⁸Gastroenterology Department, Hospital Universitario de Henares, Coslada, Spain.

²⁹Gastroenterology Department, Hospital General Universitario Dr Balmis de Alicante and Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), CIBERehd, Alicante, Spain.

³⁰Gastroenterology Department, Hospital General Universitario de Valencia, Valencia, Spain.

³¹Gastroenterology Department, Hospital Universitario Infanta Elena, Valdemoro, Madrid, Spain.

³²Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.

³³Gastroenterology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; Diet, Microbiota and Health Group. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.

³⁴Gastroenterology Department, Hospital Universitario Infanta Leonor, Madrid, Spain.

³⁵Gastroenterology Department, Hospital Universitario Vitoria-Gastéiz. Vitoria, Spain.

Abstract

Background: Real-world data on the effectiveness of upadacitinib for inflammatory bowel disease (IBD) are limited.

Aims: To assess upadacitinib persistence, effectiveness, and safety in a real-world scenario.

Methods: Retrospective multicentre study of IBD patients who received upadacitinib before 31st December 2022 and at least 12 weeks before the recruitment date. Clinical effectiveness was assessed based on partial Mayo score for ulcerative colitis (UC) and Harvey-Bradshaw index for Crohn's disease (CD).

Results: We included 100 patients (68 with CD, and 32 with UC). Patients had previously received a median of four advanced therapies. Twenty-three discontinued the treatment (median follow-up 7.6 months). CD (vs. UC) (Hazard Ratio[HR] 3.7;95%Confidence Interval (CI):1.04-12.9), and age below 40 years at upadacitinib initiation (HR 2.4;95%CI:1.0-5.8) were associated with treatment discontinuation in multivariable analysis. Clinical remission for IBD was achieved in 59% of patients at week 8, 64% at week 12, and 42% at week 52. The proportion of patients with UC previously exposed to tofacitinib (n=25) who achieved clinical remission was 78% at week 12, and 50% at week 52. Factors associated with clinical remission at week 12 were UC diagnosis (Odds Ratio[OR] 4.6;95%CI:1.3-17), mild or moderate activity at baseline (OR 8;95%CI:1.1-56) and not smoking (OR 4.4;95%CI:1.5-13). Dose escalation recaptured remission in 60% of patients with relapse. Eighty percent of patients with active immune-mediated diseases or extraintestinal manifestations improved with upadacitinib. Forty-three patients reported adverse events, 11 of them serious.

Conclusion: Upadacitinib is effective and safe for treating highly refractory IBD patients, even in previously treated with JAK inhibitors.