Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial

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doi:10.1053/j.gastro.2007.12.012 Copyright © 2008 AGA Institute Published by Elsevier Inc.

Clinical–Alimentary Tract

Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial

D. , ‡, §, , , , R. Lichtenstein, §, Julius J. Deren, §, Bruce E. Sands¶, B. Hanauer#, A. Katz, Bret Lashner‡‡, H. Present§§, Shaokun Chuai‡, , Jonas H. Ellenberg‡, , Nessel‡, D. Wu, § and Rosiglitazone for Ulcerative Colitis Study Group #University of Chicago, Chicago, Illinois‡Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania‡‡Cleveland Clinic, Cleveland, OhioDivision of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaCase Western Reserve University, Cleveland, OhioDepartment of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania§Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania§§Mount Sinai School of Medicine, New York, New York¶Massachusetts General Hospital, Boston, Massachusetts Received 1 October 2007; accepted 29 November 2007. Available online 7 December 2007.

Refers to:

Continuing Medical Education Exam 1: March 2008Gastroenterology, Volume 134, Issue 3, March 2008, Pages 865-866 B. Wallace

Background & Aims: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARγ), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC).

Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (≥2-point reduction) at week 12. Clinical remission (Mayo score ≤2), endoscopic remission, and quality of life were secondary outcomes.

Results: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare.

Conclusions: Rosiglitazone was efficacious in the treatment of mild to moderately active UC.

Abbreviations: PPAR, peroxisome proliferator-activated receptor; TZD, thiazolidinedione

Supported by National Institutes of Health grant DK059961. Drug and placebo were provided by GlaxoKline. Dr has received research funding from Centocor, GlaxoKline, and Takeda Pharmaceuticals North America. In addition, Dr has served as a consultant to Centocor, with payments being made to the Trustees of the University of Pennsylvania; he has served as a consultant to P & G Pharmaceuticals, Inc, Berlex, Elan, Synta, Shire, and Millennium. Dr has served as an expert witness for legal issues for Prometheus Labs. Dr Lichtenstein has received research support from Abbott Corporation, Bristol-Myers Squibb Corporation, Centocor, Inc, Intesco Corporation, Millenium Pharmaceuticals, Protein Design Labs, Protomed Scientific, Salix Pharmaceuticals, and Shire Pharmaceuticals; he also has received consultant fees from Abbott Corporation, Axcan Corporation, Bristol-Myers Squibb Corporation, Centocor, Inc, Elan, Proctor & Gamble, Prometheus Laboratories, Inc, Protein Design Labs, Protomed Scientific, Salix Pharmaceuticals, Schering-Plough Corporation, Serono, Shire Pharmaceuticals, Kline Beecham Corporation, Synta Pharmaceuticals, UCB, and Wyeth. Dr Lichtenstein is on the Speaker’s Bureau of the following companies: Axcan Corporation, Centocor, Inc, Proctor & Gamble, Salix Pharmaceuticals, Schering-Plough Corporation, and Shire Pharmaceuticals. Dr Sands has received consultant fees from Centocor, Inc, Abbott Laboratories, Cerimon Pharmaceuticals, Inc, Shire, and Proctor & Gamble Pharmaceuticals, Inc; he also has received research support from Centocor, Inc, Abbott Laboratories, and Cerimon Pharmaceuticals, Inc. Dr Wu has received research support from & and Centocor, Inc. Dr Deren reports having served as a consultant to Centocor, Inc, and UCB. Use of the Inflammatory Bowel Disease Questionnaire, authored by Dr Jan Irvine was made under license from McMaster University, Hamilton, Canada. Clinical trial registration: clinicaltrials.gov #NCT00065065.Address requests for reprints to: D. , MD, MSCE, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 7th Floor Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104-6021. fax: .

Gastroenterology Volume 134, Issue 3, March 2008, Pages 688-695