Short Course of COX-2 Inhibitor May Be Safe for IBD

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Short Course of COX-2 Inhibitor May Be Safe for IBD

By Karla Gale

NEW YORK (Reuters Health) Feb 15 - In a multinational prospective pilot safety trial involving patients with ulcerative colitis in remission, a 14-day course of the cyclooxygenase-2 (COX-2) inhibitor celecoxib did not result in disease exacerbation, investigators report in the February issue of Clinical Gastroenterology and Hepatology.

A second report by European investigators suggests that nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) can quickly induce relapse in patients with Crohn's disease and ulcerative colitis. However, they also observed that short-term treatment with a selective COX-2 inhibitor or with low-dose aspirin is well tolerated.

Patients with inflammatory bowel disease often have arthralgia, sacroiliitis, and ankylosing spondylitis, Dr. J. Sandborn told Reuters Health.

"Historically, there's not been a robust body of literature" regarding NSAID use in patients with inflammatory bowel disease," he added. "There have been case reports and case series that have suggested that older medications lead to increased rates of relapse in these patients."

"In general," he continued, "gastroenterologists have counseled patients with inflammatory bowel disease to not take anti-inflammatory drugs. But when the COX-2 inhibitors came out, we wondered if the risk would be different."

Dr. Sandborn, from Mayo Clinic in Rochester, Minnesota, and his colleagues recruited patients with ulcerative colitis in remission. They were randomly assigned to celecoxib (Celebrex; Pfizer) 200 mg twice daily for 14 days (n = 112) or placebo (n = 110).

There was no difference in rates of ulcerative colitis exacerbation between the two groups (3% versus 4%). Likewise, the two groups were similar in mean Mayo Clinic scores, stool frequency, rectal bleeding, histopathology, and adverse event frequency.

"But we have yet to test celecoxib in patients in relapse, and we have not addressed the risk-benefit ratio," Dr. Sandborn cautioned. "What our results do say is that at least in this subgroup of patients you can use COX-2 inhibitors for short-term use."

In the second paper, Dr. Ken Takeuchi, from Guy's, King's, St. ' Medical School in London and associates studied patients with ulcerative colitis and Crohn's disease in clinical remission.

In the first trial assessing conventional NSAIDs, patients were placed on naproxen (500 mg twice daily, n = 32), diclofenac (75 mg twice daily, n = 29), indomethacin (75 mg twice daily, n = 22) or the non-NSAID acetaminophen (1 g three times daily, n = 26).

Results showed that 17% to 28% of patients on NSAIDs, but none taking acetaminophen, experienced relapse within 2 to 9 days of starting the study.

In the second trial, 20 patients each were assigned acetaminophen (1 g 3 times daily), naproxen (500 mg twice daily), nabumetone, a non-acidic pro-NSAID (1 g twice daily), the COX-2 inhibitor nimesulide (100 mg twice daily), or aspirin (75 mg once a day).

Four patients taking naproxen and four taking nabumetone experienced relapses (on days 2 to 7), compared with one receiving acetaminophen and one receiving nimesulide (on days 22 and 29). All cases of relapse were associated with increased fecal calprotectin, a measure of inflammation in the GI tract.

Dr. Takeuchi's team infers that the mechanism inducing flares requires concurrent inhibition of both COX-1 and COX-2.

"The COX-2 inhibitor part of that study corroborates our work, and the relapse rate that they saw with the traditional anti-inflammatory drugs corroborates what people have believed for years," Dr. Sandborn commented. And even though a 20% relapse rate may seem to be fairly low, he added, "relapse in inflammatory bowel disease is not necessarily a trivial clinical event."

He believes that the results of the two studies set the stage for larger, prospective trials of COX-2 inhibitors in patients with inflammatory bowel disease. However, such trials will most likely have to wait until the cardiovascular disease risk from COX-2 inhibitors has been clarified.

In a related editorial, Dr. R. Korzenik and Dr. K. Podolsky from Harvard Medical School in Boston remark that "the action of COX-2 inhibition in active disease may be very different, and the present data on safety in patients in remission cannot be extrapolated to patients with active disease."

Nevertheless, they conclude," with the current information, celecoxib is safe in certain inflammatory bowel disease patients for short-term use, an important, even if small, advance."

Clin Gastroenterol Hepatol 2006;4.