Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.

Background:  The study was conducted to gain knowledge about the use of peroxisome proliferator-activated receptors (PPARs), such as rosiglitazone, in reducing colonic inflammation in ulcerative colitis.

Objective:  The purpose of the study was to test whether rosiglitazone is superior to placebo for patients with mild to moderately active ulcerative colitis.

Methods:  The study was a randomized, double-blind, placebo-controlled, parallel trial.  Patients were included in the study if they suffered from mild to moderate active ulcerative colitis and had been treated with mesalamine 2000mg/day or greater for at least four weeks immediately before randomization or if they were intolerant to mesalamine.  Patients were allowed to stay on stable doses of concomitant medications such as corticosteroids or azothioprine.  Patients were excluded if they had evidence of infectious colitis, were pregnant or breast-feeding, or had liver disease, contraindication to sigmoidoscopy, heart failure, an active malignancy, or diabetes mellitus requiring medications.  A total of 105 patients were randomized to receive rosiglitazone (n= 53) 4mg twice daily or placebo (n=53) for a total of 12 weeks.  The primary outcome measure was clinical response defined as a 2-point or greater decrease in Mayo score from baseline.  Secondary outcome measures were a decrease of 3 or more points in the Mayo score, clinical remission, and endoscopic remission.  Power was calculated at 80% for the primary outcome, and investigators used intention to treat analysis.

Results:  A total of 75 patients (rosiglitazone = 42, placebo = 33) completed the study.  After 12 weeks of therapy, 23 patients (44%) in the rosiglitazone group and 12 patients (23%) in the placebo group achieved a Mayo score decrease of greater than or equal to 2 points (P = 0.03).  With regard to secondary endpoints, 19 (37%) patients treated with rosiglitazone and 7 (13%) patients treated with placebo achieved clinical response by way of at least a 3-point reduction in Mayo score (P = 0.01).  Clinical remission was achieved in 9 patients (17%) treated with rosiglitazone compared to 1 patient (2%) treated with placebo (P = .01).  The authors concluded that rosiglitazone is superior to placebo for induction of clinical response and clinical remission among patients with mild to moderate ulcerative colitis.

Strengths:  An appropriate study design is a strength of the study.  Primary and secondary outcomes were easily and objectively measured.  The duration of the study allowed for a treatment effect to be seen while minimizing the risk of adverse effects. 

Weaknesses:  The mesalamine dose in which patients were considered failing is only a regular maintenance dose.  Patients should have received the maximum dose of protocol medications before being considered for rosiglitazone therapy.  Also, endoscopic results were not reported after twelve weeks of therapy, and there were a large number of dropouts.  There were also no reports of compliance.

Conclusion:  Rosiglitazone should not be used clinically until future studies gain more insight about this indication.  The possible benefit of taking rosiglitazone should also be heavily weighed against the risks involved with taking this drug.  Larger, long-term studies are needed to further evaluate the safety and efficacy of PPARs as therapy for ulcerative colitis.

Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, et al. Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.  Gastroenterology. 2008; 134: 688-695.

Dana Stone, PharmD Candidate

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