A review of infliximab use in ulcerative colitis

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doi:10.1016/j.clinthera.2008.02.014 Copyright © 2008 Published by Elsevier Inc.

A review of infliximab use in ulcerative colitis

Sheila M. Wilhelm PharmD, BCPS, Kathleen A. McKenney, N. Rivait and Pramodini B. Kale-Pradhan PharmD1, 2, Department of Pharmacy Services, Harper University Hospital, Detroit, Michigan, USASt. Hospital and Medical Center, Wayne State University, Detroit, Michigan, USA Accepted 2 January 2008. Available online 13 March 2008.

Abstract

Background: Infliximab is a chimeric immunoglobulin G1κ monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-α, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-α found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohn's disease (CD), with documented success. Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC. Objective: The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment. Methods: A search of MEDLINE was conducted (1950–November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized. Results: Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey. Conclusions: Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximab's impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.

Key words: infliximab; ulcerative colitis; cost; quality of life; steroid refractory.

Address correspondence to: Pramodini B. Kale-Pradhan, PharmD, Department of Pharmacy Services, Wayne State University, St. Hospital and Medical Center, 22101 Moross Road, Detroit, MI 48236–2148.

Clinical Therapeutics Volume 30, Issue 2, February 2008, Pages 223-230