Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits

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Eur J Clin Pharmacol. 2003 Jun;59(2):169-75. Epub 2003 Apr 16.

Outcome trials of COX-2 selective inhibitors: global safety evaluation

does not promise benefits.

Gomez Cerezo J, Lubomirov Hristov R, Carcas Sansuan AJ, Vazquez

JJ.

Department of Medicine, School of Medicine, Autonomous University of

Madrid and Service of Internal Medicine, " La Paz " University Hospital,

Madrid, Spain.

BACKGROUND: Gastrointestinal toxicity is the most frequent adverse

effect associated with nonsteroidal anti-inflammatory drug use. The most

clinically relevant side effects of this toxicity are ulcer

complications, including perforation, obstruction, or bleeding.

Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed

as a safer alternative to traditional, nonsteroidal anti-inflammatory

drugs and they are currently widely used in clinical practice. The aim

of this review was to analyze the available evidence and then critically

evaluate the outcome trials supporting the use of coxibs in terms of

their clinical gastrointestinal benefits and global safety. METHODS: All

published clinical trials on selective COX-2 inhibitors were identified

by searching Medline, the World Wide Web (WWW), and abstracts in

Congress proceedings. From these, we selected randomized trials that

clinically evaluated relevant safety outcome measures. Papers only

describing endoscopic evaluation were excluded. RESULTS: Our search

yielded three outcome trials and two pooled safety analyses. The outcome

studies supporting the gastrointestinal and global safety of coxibs were

found to be biased in their design, analysis, and dissemination, and

interpretation of a clinical benefit. Cost considerations would make the

use of coxibs acceptable only in patients at high gastrointestinal risk.

CONCLUSIONS: The association of the reduced gastroerosive potential of

coxibs with improved meaningful outcomes is debatable. Bias in the

design of the trials, selection of outcome measures, post-hoc changes in

analysis and the variables used, as well as flaws in the publication and

reporting of trial results cast serious doubts on the gastrointestinal

and global safety profile of coxibs. In addition, their high cost and

the lack of clear identification of patients that would benefit most

from treatment means the effectiveness of these drugs is uncertain at

the moment.

PMID: 12698301

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