DDW: A Bit of Good News for Rosiglitazone (Avandia), With Ulcerative Colitis

WASHINGTON, May 21 -- The suddenly embattled diabetes drug rosiglitazone (Avandia) is an effective treatment for mild-to-moderate ulcerative colitis, researchers said here.

In a randomized, double-blind, placebo-controlled study, nearly half of rosiglitazone patients had a clinical response, compared with about one in four on placebo, according to James Lewis, M.D., of the University of Pennsylvania.

The drug also significantly improved clinical remission (at P=0.01), Dr. Lewis said during Digestive Disease Week.

The report comes as controversy swirls around the drug because of a study suggesting use of the drug is associated with 43% increase in the risk of myocardial infarction in diabetes patients. (Meta-Analysis Links Rosiglitazone (Avandia) to Risk of Myocardial Infarction)

But Dr. Lewis said in an interview that patients in the study "did not have significant cardiovascular complications." There were no myocardial infarctions, he said.

The main adverse effect, Dr. Lewis said, was lower- extremity swelling, which is "a known side effect of this class of medications" - the thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors.

He said serious adverse events were rare in the study and did not differ between the placebo and rosiglitazone arms.

The first line of treatment for the disease is drugs containing 5-aminosalicylic acid, but some patients either don't respond or can't take those medications, he said.

Rosiglitazone "is a novel second-line therapy," he said.

The study enrolled 105 patients and randomized them to either 4 mg orally of rosiglitazone a day or placebo for 12 weeks.

The primary endpoint was at least a two-point reduction on the Disease Activity Index. Secondary endpoints included at least a three-point reduction on that scale, clinical remission (a Disease Activity Index of two or lower at the end of the study), and endoscopic remission (a Disease Activity Index of less than two at the end of the study and normal mucosa).

The study found:

• 44% of rosiglitazone patients met the primary endpoint, compared with 23% of placebo patients, a difference that was significant at P=0.03.
• 37% of rosiglitazone patients had at least a three-point reduction in Disease Activity Index, compared with 13% of placebo patients, a difference that was significant at P=0.01.
• 17% of rosiglitazone patients had a clinical remission, compared to 2% of those given placebo, which was significant at P=0.01.

There was a trend toward endoscopic remission among rosiglitazone patients, but it was not significant.

For patients who can't take or don't respond to first-line therapy, the study may allow them to avoid steroid treatment, commented Maria Abreu, M.D., of Mount Sinai in New York, who moderated the press conference where the study was discussed.

"I'm delighted for my patients," she said. "Even though the response rates don't knock your socks off, it's still very significant because the next step is steroids."