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10/25/2000

Celecoxib Beats NSAIDs When No Aspirin Used

Kate Traynor

Fewer ulcer symptoms and complications develop in patients who take high-dose celecoxib rather than a traditional nonsteroidal anti-inflammatory drug (NSAID) to relieve osteoarthritis or rheumatoid arthritis, but this difference practically disappears with the addition of low-dose aspirin, according to the results of a large North American study.

Symptoms and complications of gastrointestinal (GI) ulcers occurred 59 percent more often in patients given standard dosages of the NSAID ibuprofen or diclofenac than in patients who received celecoxib 400 mg twice daily. Celecoxib specifically inhibits cyclooxygenase type 2, leaving alone the enzyme's other isoform, which helps to maintain the integrity of GI mucosa. Ibuprofen and diclofenac inhibit both isoforms of cyclooxygenase.

Among the 20 percent of patients who also took 325 mg or less of aspirin daily, ulcer complications occurred at the annualized rate of 2 percent, regardless of which pain reliever had been assigned. Differences in the incidence of ulcer symptoms and complications were also insignificant.

Ulcer complications developed 35 percent less frequently in celecoxib users who did not use aspirin than in patients who took an NSAID but not aspirin.

The study, which appeared in the Sept. 13 issue of the Journal of the American Medical Association (PDF), also reported the incidence of other adverse events. Bleeding-related adverse events and kidney and liver complications were significantly less common in arthritis patients who took celecoxib than in those who used an NSAID.

The incidence of adverse cardiovascular events, such as myocardial infarction, was similar in the celecoxib and NSAID groups, regardless of aspirin use.

These findings came from the Celecoxib Long-term Arthritis Safety Study (CLASS), which compared the safety of standard therapeutic dosages of ibuprofen or diclofenac with an intentionally high dosage of celecoxib. CLASS data were obtained from 7,968 patients at 326 medical centers in the United States and Canada.

The authors noted that many of the osteoarthritis and rheumatoid arthritis patients typically treated in clinical practice would have been excluded from the study, which did not enroll patients with active GI disease. Other patients excluded from the study were those who had had cancer within the past five years and patients with kidney, liver, or clotting disorders.

Patients who used glucocorticoids or disease-modifying antirheumatic drugs were eligible for the study.

During the trial, which ran from September 1998 to this past March, 3,987 adults age 18 and older were randomly assigned to the celecoxib group. A group of 3,981 adults with similar characteristics was assigned to NSAID treatment, with 1,985 patients randomly chosen to receive ibuprofen 800 mg three times a day and 1,996 to receive diclofenac 75 mg twice daily.

According to the package insert for celecoxib, the recommended daily dose of celecoxib is 200 mg for osteoarthritis treatment and 200–400 mg for treatment of rheumatoid arthritis. CLASS enrollees in the celecoxib group received two to four times the recommended dosage. The study authors indicated that they selected this amount in order to assess the safety of celecoxib at a high dosage.

When given at a dosage higher than the recommended amount, celecoxib does not produce a better therapeutic response than when given at a lower dosage, the authors noted.

Patients who took less than 70 percent of their assigned medication were considered noncompliant and withdrawn from the study. Other patients withdrew from the study because their drug did not adequately control arthritis symptoms or adverse events occurred during treatment.

In all, 2,376 patients in the celecoxib group and 2,197 in the NSAID group completed at least six months of treatment.

Celecoxib is manufactured by Pharmacia Corp. under the brand name Celebrex. This study was funded by Pharmacia, and all study authors are employees or paid consultants of the company.