Clin Gastroenterol Hepatol. 2022 Oct;20(10):2337-2346.e3.doi: 10.1016/j.cgh.2021.12.030. Epub 2021 Dec 27.

Geert D'Haens ¹, Julian Panés ², Edouard Louis ³, Ana Lacerda ⁴, Qian Zhou ⁵, John Liu ⁶, Edward V Loftus Jr ⁷

Author information

¹Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, Netherlands. Electronic address: g.dhaens@amsterdamumc.nl.

²Inflammatory Bowel Diseases Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

³Department of Gastroenterology, University Hospital CHU of Liège, Liège, Belgium.

⁴Global Pharmaceutical Research and Development, AbbVie Inc, North Chicago, Illinois.

⁵Data and Statistical Sciences, AbbVie Inc, North Chicago, Illinois.

⁶Pharmacovigilance and Patient Safety, AbbVie Inc, North Chicago, Ilinois.

⁷Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.

Abstract

Background & aims: The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn's disease.

Methods: Patients who completed the 52-week study (CELEST) received upadacitinib in the CELEST OLE as follows: those who had received immediate-release upadacitinib 3, 6, or 12 mg twice daily or 24 mg once daily (QD) received extended-release upadacitinib 15 mg QD and those who had received immediate-release upadacitinib 12 or 24 mg twice daily as rescue therapy received extended-release upadacitinib 30 mg QD. If any patient initiating upadacitinib 15 mg QD in CELEST OLE lost response at or after week 4, the dose was escalated to upadacitinib 30 mg QD (dose-escalated group). Clinical, endoscopic, inflammatory and quality-of-life measures were assessed.

Results: A total of 107 CELEST study completers entered CELEST OLE. The proportion of patients with clinical remission 2.8/1.0 was maintained between week 0 and month 30 in all groups (month 30: 15 mg, 61%; 30 mg, 54%; dose-escalation, 55%). Endoscopic response was maintained in all groups (month 24: 68%, 67%, and 40%, respectively). The rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, infections, serious infections, herpes zoster, and creatine phosphokinase elevation were higher with upadacitinib 30 mg vs 15 mg.

Conclusion: Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed in patients with Crohn's disease receiving upadacitinib. Safety over 30 months was consistent with the known safety profile of upadacitinib.

Clinicaltrials: gov ID no: NCT02782663.