June 18, 2010 (Rome, Italy) — Patients with rheumatoid arthritis and osteoarthritis treated with a selective cyclooxygenase-2 (COX-2) inhibitor for inflammation and pain were 4 to 5 times less likely to develop clinically significant upper and lower gastrointestinal problems than those who were treated with diclofenac, a nonselective nonsteroidal anti-inflammatory drug, plus a proton pump inhibitor, according to results of the Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis (CONDOR) study. The study was published online June 17 in The Lancet to coincide with its presentation here at the European League Against Rheumatism (EULAR) Congress 2010.
Lead author of the study, Francis K.I. Chan, MD, from the Department of Medicine and Therapeutics, Prince of Wales Hospital, at the Chinese University of Hong Kong, called these findings relevant for patients who require long-term anti-inflammatory therapy and who are at increased gastrointestinal risk but not increased cardiovascular risk .
The study's authors said that these findings should encourage a review of treatment guidelines for arthritis patients.
CONDOR was a large 6-month double-blind randomized trial of patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk recruited from 196 centers in 32 countries. Patients were 60 years of age and older or 18 years and older with previous gastrointestinal ulceration. All patients were Helicobacter pylori–negative.
A total of 4484 patients were randomly assigned to treatment with celecoxib 200 mg twice daily (n = 2238) or slow-release diclofenac 75 mg twice daily plus the proton pump inhibitor omeprazole 20 mg daily (n = 2246).
The primary end point was a composite of clinically significant events occurring throughout the gastrointestinal tract, including hemorrhage, obstruction, perforation, clinically significant anemia, and acute gastrointestinal hemorrhage of unknown origin. Clinically significant anemia was defined as a decrease in hemoglobin of 20 g/L or more or a decrease in hematocrit of at least 10%.
The primary end point was met in 20 patients (0.9%) treated with celecoxib and in 81 patients (3.8%) treated with diclofenac plus omeprazole (P < .0001). Early withdrawal because of gastrointestinal adverse events occurred in 114 patients (6%) in the celecoxib group and in 167 patients (8%) in the diclofenac plus omeprazole group (P = .0006).
In an accompanying editorial, Elham Rahme, MD, and Sasha Bernatsky, MD, from McGill University in Montreal, Quebec, stated that the authors of CONDOR believe that the risk of lower gastrointestinal bleeding is as important as the risk of upper gastrointestinal bleeding.
Drs. Rahme and Bernatsky say that the decreased risk in this study was driven mainly by a hemoglobin decrease, not by documented lower gastrointestinal bleeds. "Thus, advice to revise existing guidelines accordingly might be premature," the editorialists write.
Commenting on this study at the EULAR meeting, Rainer Wigand, MD, professor of rheumatology at the University of Frankfurt and rheumatologist in private practice in Frankfurt, Germany, said that "the choice of this end point is quite new. This is the first study to look at the development of clinically significant anemia, which is what kills our elderly patients with clinically silent lower gastrointestinal bleeding."
Elderly patients with anemia due to clinically silent lower gastrointestinal bleeding typically die from breaking a hip in a fall and then deteriorating, he explained. Previous studies of the gastrointestinal effects of treatments for arthritis have counted the number of erosive lesions and ulcers, which does not have clinical significance unless these lesions bleed, he explained.
"The study shows us that we can harm our patients by [prescribing] diclofenac plus a proton pump inhibitor. Use of celecoxib alone is very safe and provides good gastrointestinal protection — a reduction of about 80% for the primary end point," Dr. Wigand stated.
The study was funded by Pfizer. Dr. Chan reports being a consultant to Pfizer, Eisai, Takeda, and Otsuka; being international associate editor of the American Journal of Gastroenterology; and receiving grants from Pfizer and lecture fees from Pfizer, AstraZeneca, and Takeda. Dr. Rahme reports financial ties with Merck, Pfizer Canada, Boehringer Ingelheim, Chiesi Farmaceutici, Bayer, and Ethypharm. Dr. Bernatsky has disclosed no relevant financial relationships. Dr. Wigand reports receiving payment for CME work from MSD, Wyeth, Pfizer, Amgen, Sanofi-Aventis, and Abbott.
Lancet. Published online June 17, 2010.
European League Against Rheumatism (EULAR) Congress 2010: Abstract THU0436. Presented June 17, 2010.
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