COMPARATIVE EFFECTIVENESS OF INHALED CORTICOSTEROIDS AND LEUKOTRIENE MODIFIERS FOR THE TREATMENT OF PERSISTENT ASTHMA IN ADULTS AND CHILDREN: A SYSTEMATIC REVIEW

 Purpose: To assess the comparative effectiveness of inhaled corticosteroids (ICSs) and leukotriene modifiers for the treatment of adults and children with persistent asthma.

 Methods:  We searched Medline, the Cochrane database, and the International Pharmaceutical Abstracts (1990 through April 2008), using terms for included drugs, indications, and study designs. We also reviewed dossiers provided by pharmaceutical companies.  We included studies of subjects with persistent asthma that compared monotherapy with inhaled corticosteroids (beclomethasone, budesonide, flunisolide, fluticasone, triamcinolone, and mometasone) to monotherapy with the included leukotriene modifiers (montelukast, zafirlukast, or zileuton).  We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks duration.  Outcomes of interest included exacerbations, control of symptoms, rescue medication use, quality of life, healthcare utilization, and mortality.
 Two reviewers independently assessed abstracts and full-text articles to identify included studies. Disagreements were resolved by consensus.  We used a structured data abstraction form to ensure consistency in appraisal for each study.  Trained reviewers abstracted data and assessed the methodologic quality (internal validity) of studies using predefined criteria based on the U.S. Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination (U.K.) criteria.  Meta-analyses were conducted for outcomes reported by a sufficient number of studies which were homogeneous enough to justify combining their results. Otherwise, the data were summarized qualitatively. Random effects models were used for the estimation of pooled effects.  We rated the overall strength of evidence (insufficient, low, moderate, or high) using standard methods from the Evidence-based Practice Centers’ Guide for Conducting Comparative Effectiveness Reviews.

 Results: We found 22 head-to-head RCTs (7 in children) comparing an ICS to a leukotriene modifier that met our inclusion criteria.  Trial duration ranged from
6 to 56 weeks.  The most common comparison found was fluticasone vs montelukast (9 RCTs).  Patients treated with leukotriene modifiers were 68% more likely to have an asthma exacerbation than those treated with ICSs (Relative Risk 1.68; 95% confidence interval 1.68, 2.15).  Patients treated with ICSs also had greater improvements in control of symptoms, reduction of rescue medication use, and quality of life.

 Conclusion: Good and fair-quality efficacy studies provide strong evidence that Inhaled corticosteroids are more effective than leukotriene modifiers for the treatment of persistent asthma in adults and children at conventional doses.