Abstract

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies

Inflamm Bowel Dis. 2020 Sep 23;izaa236. doi: 10.1093/ibd/izaa236. Online ahead of print.

William J Sandborn 1, Brian G Feagan 2, Silvio Danese 3, Christopher D O'Brien 4, Elyssa Ott 5, Colleen Marano 4, Thomas Baker 5, Yiying Zhou 4, Sheri Volger 4, Ilia Tikhonov 4, Christopher Gasink 5, Bruce E Sands 6, Subrata Ghosh 7

 
     

Author information

  • 1University of California San Diego, La Jolla, CA, USA.
  • 2Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
  • 3Humanitas Clinical Research Center-IRCCS and Humanitas University, Department of Biomedical Sciences, Milan, Italy.
  • 4Janssen Research & Development, LLC, Spring House, PA, USA.
  • 5Janssen Scientific Affairs, LLC, Horsham, PA, USA.
  • 6Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 7Institute of Translational Medicine and NIHR Biomedical Research Center, University of Birmingham, United Kingdom.

Abstract

Background: Ustekinumab is currently approved globally in Crohn's disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn's disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses.

Methods: Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed.

Results: Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81-176.67] vs ustekinumab 118.32 [95% CI, 113.25-123.55]), serious AEs (27.50 [95% CI, 23.45-32.04] vs 21.23 [95% CI, 19.12-23.51]), infections (80.31 [95% CI, 73.28-87.84] vs 64.32 [95% CI, 60.60-68.21]), serious infections (5.53 [95% CI, 3.81-7.77] vs 5.02 [95% CI, 4.02-6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00-0.93] vs 0.40 [95% CI, 0.16-0.83]) were similar between placebo and ustekinumab.

Conclusions: The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications.

Clinicaltrials.gov numbers: NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.

© Copyright 2013-2020 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.