Celecoxib Versus Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis - CONDOR

Jun 20, 2010
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Pfizer Inc.
Date Published:
01/01/2010
Date Updated:
06/20/2010
Original Posted Date:
06/20/2010
References

Description:

The goal of the trial was to evaluate treatment with celecoxib, a cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug (NSAID), versus diclofenac plus omeprazole in patients with osteoarthritis or rheumatoid arthritis.

Diclofenac is considered a nonselective NSAID, although it is relatively selective against the COX-2 isoenzyme.

Hypothesis:

Celecoxib would be more effective in preventing upper and lower gastrointestinal outcomes.

Study Design

  • Blinded
  • Parallel
  • Stratified
  • Randomized

Patient Populations:

  • Screened Applicants: 8,098
  • Enrollees: 4,484
  • Duration of Follow-up: 6 months
  • Age Range: Mean 65 years
  • Percentage Female: 83%
  • Patients at least 18 years of age with osteoarthritis or rheumatoid arthritis
  • Anticipated NSAID treatment for at least 6 months
  • Patients 18-59 years of age were required to have a history of gastroduodenal ulceration or gastroduodenal hemorrhage more than 90 days prior to enrollment
  • Helicobacter pylori negative

Exclusions:

  • Concomitant use of antiplatelet or anticoagulate medications
  • Ischemic heart disease
  • Heart failure
  • Peripheral arterial disease
  • Cerebrovascular disease
  • Gastroduodenal ulceration or gastroduodenal hemorrhage less than 90 days prior to enrollment
  • Inflammatory bowel disease
  • Gastric surgery other than patch repair
  • Erosive esophagitis
  • Gastric outlet obstruction
  • Active malignant disease
  • Alcohol or substance abuse
  • Allergy to celecoxib, diclofenac, omeprazole, or sulphonamides
  • Alanine or aspartate transaminase concentration more than 1.5 x the upper limit of normal
  • Hemoglobin <11.5 mg/dl

Primary Endpoints:

  • Composite of gastroduodenal/small-bowel/large-bowel hemorrhage, acute gastrointestinal hemorrhage of unknown origin, gastric outlet obstruction, gastroduodenal/small-bowel/large-bowel perforation, or clinically significant anemia from known or presumed gastrointestinal origin

Secondary Endpoints:

  • Patient’s Global Assessment of Arthritis
  • Clinically significant events throughout the gastrointestinal tract
  • Symptomatic ulcers
  • Moderate to severe abdominal symptoms
  • Withdrawal due to gastrointestinal adverse events
  • Cardiovascular events defined as cardiovascular death, myocardial infarction, or stroke
  • Unstable angina
  • Coronary revascularization
  • Transient ischemic attack
  • Venous and peripheral arterial vascular thrombotic events
  • Congestive heart failure

Drug/Procedures Used:

Patients with osteoarthritis or rheumatoid arthritis were randomized to celecoxib 200 mg twice daily (n = 2,238) versus diclofenac 75 mg twice daily plus omeprazole 20 mg daily (n = 2,246).

Principal Findings:

Overall 4,484 patients were randomized. In the celecoxib group, mean age was 65 years, 83% were women, 84% had osteoarthritis, and 19% had a history of gastroduodenal ulcer or bleeding.

At 6 months, the composite gastrointestinal primary outcome occurred in 0.9% of the celecoxib group versus 3.8% of the diclofenac plus omeprazole group (p < 0.0001). This was mainly due to a reduction in clinically significant anemia from known or presumed gastrointestinal origin in the celecoxib group: 15 versus 77 patients, respectively.

The Patient’s Global Assessment of Arthritis was improved 0.75 in the celecoxib group versus 0.77 in the diclofenac plus omeprazole group (p = 0.41).

Cardiovascular deaths occurred in 1 versus 0, myocardial infarctions occurred in 2 versus 2, and strokes occurred in 3 versus 3, respectively.

Interpretation:

Among patients with osteoarthritis or rheumatoid arthritis, celecoxib was associated with a reduction in composite gastrointestinal (upper and lower) events compared with diclofenac plus omeprazole.

COX-2 inhibitors have previously been shown to reduce upper gastrointestinal tract ulcerations compared with nonselective NSAIDS. This study appears to expand the benefit of celecoxib across the entire gastrointestinal tract.

It is important to note that patients were carefully screened to exclude a history of cardiovascular, cerebrovascular, or peripheral arterial disease, since COX-2 inhibitors (rofecoxib and high-dose celecoxib) and nonselective NSAIDS (diclofenac and indomethacin) have been associated with increased cardiovascular events. It is unknown if celecoxib would result in decreased gastrointestinal events compared with ibuprofen or naproxen plus a proton pump inhibitor.

References:

Chan FK, Lanas A, Scheiman J, Berger MF, Nguyen H, Goldstein JL. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. Lancet 2010;Jun 17:[Epub ahead of print].

Keywords: Upper Gastrointestinal Tract, Myocardial Infarction, Stroke, Diclofenac, Cyclooxygenase 2 Inhibitors, Ibuprofen, Peripheral Arterial Disease, Pyrazoles, Sulfones, Proton Pump Inhibitors, Indomethacin, Naproxen, Lactones, Osteoarthritis, Omeprazole, Peptic Ulcer, Helicobacter pylori, Sulfonamides, Prostaglandin-Endoperoxide Synthases


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