Investigational COX-2 inhibitor shows similar safety to diclofenac in large-scale trial

Investigators found that etoricoxib met the prespecified primary endpoint, showing a 0.95 relative risk of confirmed thrombotic cardiovascular events between it and diclofenac.

In a large-scale study, patients treated with the investigational selective COX-2 inhibitor etoricoxib showed similar rates of confirmed thrombotic cardiovascular events compared to patients treated with diclofenac, the most commonly used NSAID.

Christopher P. Cannon, MD, co-chair of the study's steering committee and a cardiologist at Brigham and Women's Hospital, Boston, and colleagues at 46 centers worldwide conducted the prospective study, called the Multinational Etoricoxib and Diclofenac Arthritis Long-Term (MEDAL) program. The preliminary findings were presented earlier this month at three scientific meetings. They are also published online in The Lancet, according to a press release from Merck & Co., the drug's developer.

The MEDAL program focused on performing a noninferiority analysis of confirmed thrombotic cardiovascular events following 18 months of daily treatment with either 60 mg or 90 mg of etoricoxib (Arcoxia, Merck) compared with 150 mg of diclofenac in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), according to the release.

Investigators found that etoricoxib met the prespecified primary endpoint, showing a 0.95 relative risk of confirmed thrombotic cardiovascular events between it and diclofenac. However, patients treated with etoricoxib showed a significantly lower confirmed rate of upper gastrointestinal (GI) clinical events, including perforations, ulcers, bleeding and obstructions, although there was no significant difference in rates of confirmed, complicated upper GI clinical events, such as obstructions and major bleeding.

Etoricoxib has been under review by the FDA since Merck filed its original New Drug Application in December 2003. It is currently available in 62 countries in Europe, Latin America, the Asia-Pacific region and Middle East/Northern Africa.

Patients included in the MEDAL program were at least 50 years old and had a clinical diagnosis of OA of the knee, hip, hand or spine, or a clinical diagnosis of RA that satisfied at least four of seven of the American Rheumatism Association 1987 revised criteria and, in the judgment of the investigator, would require chronic therapy with an NSAID. Such patients were not candidates for acetaminophen as first-line therapy due to their symptom severity.

Patients with a history of myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary intervention more than 6 months before enrollment were permitted to participate. Also, 35% of the 34,701 patients enrolled were taking low-dose aspirin and 50% used a gastroprotective agent, according to the release.

Among the 34,701 patients enrolled, 17,412 received etoricoxib and 17,289 received diclofenac. In the primary analysis, 320 etoricoxib patients and 323 diclofenac patients experienced thrombotic cardiovascular events.

The most common thrombotic cardiovascular events included heart attacks at a rate of 0.43 per 100 patient years for etoricoxib and 0.49 for diclofenac. Both groups also had a similar rate of fatal thrombotic cardiovascular events, averaging 0.17 per 100 patient years, according to the release.

For more information:
Cannon CP, Curtis SP, FitzGerald GA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Programme: a randomised comparison. Lancet. 2006;368. Published online Nov. 18, 2006. Available at www.thelancet.com.