Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis

William J Sandborn , Subrata Ghosh, Julian Panes, Stefan Schreiber, Geert D'Haens, Satoshi Tanida, Jesse Siffledeen, Jeffrey Enejosa, Wen Zhou, Othman Ahmed, Bidan Huang, Peter D. R. Higgins

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
148 Downloads (Pure)

Abstract

Background & Aims: We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC).

Methods: We performed a multicenter, double-blind, phase 2b study of 250 adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomly assigned to groups that received placebo or induction therapy with upadacitinib (7.5 mg, 15 mg, 30 mg, or 45 mg, extended release), once daily for 8 weeks. The primary endpoint was the proportion of participants who achieve clinical remission according to the adapted Mayo score at week 8. No multiplicity adjustments were applied.

Results: At week 8, 8.5%, 14.3%, 13.5%, and 19.6% of patients receiving 7.5 mg, 15 mg, 30 mg, or 45 mg upadacitinib, respectively, achieved clinical remission compared with none of the patients receiving placebo (P = .052, P = .013, P = .011, and P = .002 compared with placebo, respectively). Endoscopic improvement at week 8, defined as endoscopic subscore of ≤ 1, was achieved in 14.9%, 30.6%, 26.9%, and 35.7% of patients receiving upadacitinib 7.5 mg, 15 mg, 30 mg, or 45 mg, respectively, compared with 2.2% receiving placebo (P = .033, P < .001, P < .001, and P < .001 compared with placebo, respectively). One event of herpes zoster and 1 participant with pulmonary embolism and deep venous thrombosis (diagnosed 26 days after treatment discontinuation) were reported in the group that received upadacitinib 45 mg once daily. Increases in serum lipid levels and creatine phosphokinase with upadacitinib were observed.

Conclusion: In a phase 2b trial, 8 weeks of treatment with upadacitinib was more effective than placebo for inducing remission in patients with moderately to severely active UC. (ClinicalTrials.gov, Number: NCT02819635)

Original languageEnglish
Pages (from-to)2139-2149.e14
Number of pages25
JournalGastroenterology
Volume158
Issue number8
Early online date22 Feb 2020
DOIs
Publication statusPublished - Jun 2020

Bibliographical note

Funding Information:
The writing of this manuscript was funded by AbbVie Inc. The authors and AbbVie scientists designed the study and analyzed and interpreted the data. AbbVie funded the research and provided writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the manuscript; the authors maintained control over the final content.

Publisher Copyright:
© 2020 The Authors

Keywords

  • U-ACHIEVE
  • inflammatory bowel disease
  • IBD treatment
  • selective JAK1 inhibitor
  • IBD Treatment
  • Selective JAK1 Inhibitor
  • Inflammatory Bowel Disease

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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