Ulcerative colitis may respond to treatment with rosiglitazone

Last Updated: 2008-04-03 13:48:55 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Rosiglitazone is safe and efficacious in the treatment of mild to moderately active ulcerative colitis, according to findings published in the March issue of Gastroenterology.

"Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PRAR-gamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC)," Dr. James D. Lewis, of the University of Pennsylvania School of Medicine, Philadelphia, and colleagues write.

In a multicenter, randomized, double-blind clinical trial, the researchers compared the efficacy of rosiglitazone 4 mg orally twice a day versus placebo twice a day for 12 weeks in 105 patients with mild to moderately active UC. They used the Mayo score to measure disease activity. The main outcome was clinical response, which was defined as a 2-point or greater reduction in the Mayo score.

After 12 weeks, 23 (44%) rosiglitazone-treated patients and 12 (23%) placebo-treated patients achieved a clinical response (p = 0.03).

"In logistic regression analysis, age and smoking status were identified as confounders," Dr. Lewis and colleagues explain. "After adjusting for these factors, the association between treatment with rosiglitazone and clinical response was stronger (unadjusted odds ratio 2.7, p = 0.02; adjusted odds ratio 4.0, p = 0.005)."

Overall, nine patients (17%) treated with rosiglitazone and one patient (2%) treated with placebo achieved clinical remission (p = 0.01). Endoscopic remission was uncommon, and was achieved in only 8% of rosiglitazone-treated patients and 2% of placebo-treated patients (p = 0.34).

Clinical improvement was observed as early as 4 weeks after starting treatment (p = 0.049). Quality of life was improved significantly at week 8 (p = 0.04). However, significant improvement in quality of life was not seen at week 4 or week 12. Serious adverse events were rare.

The team cautions that any benefits of rosiglitazone must be weighed against potential toxicity, particularly "in light of the recent data regarding the risk of myocardial infarction and fracture." They also stress that their results pertain to short-term use, and "there are no data on the long-term safety and efficacy of rosiglitazone for maintenance of response."

Gastroenterology 2008;134:688-695.