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

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Abstract

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.

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Authors and Affiliations

  1. Department of Medicine, School of Medicine, Autonomous University of Madrid and Service of Internal Medicine, "La Paz" University Hospital, Madrid, Spain

    Jorge Gomez Cerezo & Juan J. Vázquez Rodríguez

  2. Servicio de Farmacología Clínica, Hospital Universitario "La Paz", Paseo de la Castellana 261, 28046, Madrid, Spain

    Rubin Lubomirov Hristov

  3. Department of Pharmacology and Therapeutics, School of Medicine, Autonomous University of Madrid and Service of Clinical Pharmacology, "La Paz" University Hospital, Madrid, Spain

    Antonio J. Carcas Sansuán

Authors
  1. Jorge Gomez Cerezo
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  2. Rubin Lubomirov Hristov
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  3. Antonio J. Carcas Sansuán
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  4. Juan J. Vázquez Rodríguez
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Corresponding author

Correspondence to Rubin Lubomirov Hristov.

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Gomez Cerezo, J., Lubomirov Hristov, R., Carcas Sansuán, A.J. et al. Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits. Eur J Clin Pharmacol 59, 169–175 (2003). https://doi.org/10.1007/s00228-003-0579-1

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  • DOI: https://doi.org/10.1007/s00228-003-0579-1

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