Long-Term Safety of Upadacitinib in Patients With Inflammatory Bowel Disease: Integrated Analysis of Phase 2/3 Studies

Panaccione R, Panés J, Peyrin-Biroulet L, Colombel JF, Lindsay JO, Baert F, Atreya R, Vermeire S, Fujii T, Dubcenco E, Klaff J, Duncan B, Suravaram S, Fish I, Lacerda AP, Vladea R, Ford S, Shah S, Anyanwu SI, Rubin DT (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Clinical Gastroenterology and Hepatology WB Saunders

DOI: 10.1016/j.cgh.2026.02.018

Abstract

Background & Aims Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). We assessed the long-term safety of UPA in both inflammatory bowel disease (IBD) entities. Methods Safety from 6 UC/CD trials assessed UPA 45 mg (UPA45) once daily (QD) induction, UPA 15 mg and 30 mg (UPA 15/30 QD) maintenance/long-term extension (LTE) doses, and rescue therapy (UPA30 QD). Adverse events (AEs) were reported as events per 100 patient-years (E/100 PY). Results Overall, 2118 patients received placebo (PBO; n = 725) or UPA45 (n = 1393) induction; 1419 received PBO (n = 468), UPA15 (n = 471), or UPA30 (n = 480) maintenance/LTE. During maintenance/LTE, UPA cumulative exposure was 5149.3 patient-years (n = 1910). Median treatment duration was 8.7 weeks (interquartile range [IQR], 8.0–12.0 weeks) for UPA45 induction; median maintenance/LTE treatment duration was 58.1 weeks (IQR, 30.4–164.0 weeks) for UPA15, and 130.9 weeks (IQR, 39.4–175.1 weeks) for UPA30. AE incidence was comparable between UPA and PBO during induction and maintenance/LTE; AEs leading to study drug discontinuation and serious or severe AEs were lower with UPA. During maintenance/LTE, rates (UPA15/30 vs PBO) of venous thromboembolic events (0.3/0.4 vs 0 E/100 PY), gastrointestinal perforations (0.4/<0.1 vs 0.8 E/100 PY), and AEs leading to death (0.2/<0.1 vs 0 E/100 PY) were low. Herpes zoster, neutropenia, lymphopenia, creatine phosphokinase elevation, hepatic disorder, and COVID-19 were higher across UPA groups vs PBO; COVID-19 and herpes zoster were among the most common AEs during maintenance. Conclusions Long-term, UPA was generally well-tolerated. This integrated analysis supports the favorable safety profile of UPA and treatment decisions for patients with IBD. ClinicalTrials.gov , Numbers: NCT02819635 , NCT03653026 , NCT03006068 , NCT03345836 , NCT03345849 , and NCT03345823 .

Authors with CRIS profile

Raja Atreya Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

University of Calgary CA Canada (CA) Centro de Investigación Biomédica en Red - Enfermedades Hepáticas y Digestivas (CIBERHD) ES Spain (ES) Université de Lorraine FR France (FR) AbbVie Inc. US United States (USA) (US) AZ Delta BE Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) Institute of Science Tokyo (ISCT) / 東京科学大学 JP Japan (JP) University of Chicago US United States (USA) (US) Icahn School of Medicine at Mount Sinai US United States (USA) (US) Queen Mary University of London GB United Kingdom (GB)

How to cite

APA:

Panaccione, R., Panés, J., Peyrin-Biroulet, L., Colombel, J.F., Lindsay, J.O., Baert, F.,... Rubin, D.T. (2026). Long-Term Safety of Upadacitinib in Patients With Inflammatory Bowel Disease: Integrated Analysis of Phase 2/3 Studies. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2026.02.018

MLA:

Panaccione, Remo, et al. "Long-Term Safety of Upadacitinib in Patients With Inflammatory Bowel Disease: Integrated Analysis of Phase 2/3 Studies." Clinical Gastroenterology and Hepatology (2026).

BibTeX: Download