Variability in patient responses to COX-2 inhibitors could lead to the development of diagnostic tests to select who should continue use of the drugs, a study in the January issue of Gastroenterology suggests.

The study of 50 patients found that "even healthy individuals respond quite differently to coxibs," Susanne Fries (University of Pennsylvania) et al., said.

"This variance might confound the detection of cardiovascular events attributable to drug exposure. On the other hand, inter-individual variability in drug response might be exploited to identify patients in whom the drug exhibits unique efficacy or in whom the evolution of cardiovascular risk is accelerated," the researchers noted.

The authors add that animal models of COX-2s suggest "the degree of selectivity attained in vivo may relate to cardiovascular outcomes, including hypertension, myocardial infarction and stroke"

The randomized, double-blind, placebo-controlled study examined responses both within and between individuals to Merck's Vioxx (rofecoxib, 25 mg) and Pfizer's Celebrex (celecoxib, 200 mg).

The study found no difference in the degree of COX-2 inhibition between Vioxx (44.8%) and Celebrex (47.5%).

However, the study found considerable variability with regard to COX-2 and COX-1 inhibition among the patients and that about 30% of the variability "may be attributable to inter-individual variability," or the individual's genetic make-up.

"Validated genetic markers might be usefully combined with biomarkers of atherogenesis (e.g., blood pressure), kinetic and dynamic parameters of drug action to identify individuals who accelerate their development of cardiac risk during treatment with coxibs," the study states.

"Such a strategy might conserve the value of extended dosing with selective inhibitors of COX-2 for patients at low-risk of cardiovascular diseases who have previously exhibited gastrointestinal intolerance to traditional NSAIDs," the authors concluded.

Vioxx and Pfizer's Bextra (valdecoxib) were withdrawn from the market due to concerns about cardiac safety. Celebrex remains on the market with warnings; Pfizer is funding a 20,000-patient study to assess the cardiac safety of the drug (¹ Also see "Celebrex Heart Risk To Be Assessed By Cleveland Clinic In Pfizer-Funded Study" - Pink Sheet, 19 December, 2005., p. 18).

An FDA advisory committee will review the agency's actions taken with regard to COX-2 inhibitor safety on Feb. 10.

COX-2s Patient Response Variability Could Lead To Diagnostic Tests

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