Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children.

BACKGROUND: Anti-leukotrienes agents are currently being studied as alternative first line agents to inhaled corticosteroids in mild to moderate chronic asthma.

OBJECTIVES: To compare the safety and efficacy of anti-leukotriene agents with inhaled glucocorticoids (ICS) and to determine the dose-equivalence of anti-leukotrienes to daily dose of ICS.

SEARCH STRATEGY: Medline (1966 to Jan 2002), Embase (1980 to Jan 2002), and Cinahl (1982 to Jan 2002) were searched and reference lists of review articles and trials. We contacted colleagues and international headquarters of anti-leukotrienes producers.

SELECTION CRITERIA: Randomised controlled trials that compared leukotriene antagonists with inhaled corticosteroids during a minimal 30-day intervention period in asthmatic patients aged 2 years and older.

DATA COLLECTION AND ANALYSIS: Two reviewers performed assessments of methodological quality and data extraction independently and blindly. The primary outcome was the rate of exacerbations requiring systemic corticosteroids. Secondary outcomes included lung function, indices of chronic asthma control, adverse effects and withdrawal rates.

MAIN RESULTS: 14 trials met the inclusion criteria; 10 were of high methodological quality; 8 are published in full-text. All were in mild-to-moderate chronic asthma, Two included children or adolescents. Trial duration was 4 - 37 weeks. In most trials, daily dose of ICS was 400 mcg of beclomethasone-equivalent. Patients treated with anti-leukotrienes were 60% more likely to suffer an exacerbation requiring systemic steroids [12 trials; Relative Risk 1.61; 95% Confidence Interval (CI) 1.15, 2.25]. Significant differences favouring ICS were noted in most secondary outcomes, eg improvement in FEV1 [7 trials; Weighted Mean Difference 120 ml; 95% CI: 80, 170 ml ]; symptom scores [5 trials: Standardized Mean Difference 0.3; 95% CI 0.2, 0.4]. Other significant benefits of ICS were seen for nocturnal awakenings, rescue medication use, and quality of life. Risk of side effects was not different between groups, but anti-leukotriene therapy was associated with 30% increased risk of "withdrawals for any cause" or "withdrawals due to poor asthma control".

REVIEWER'S CONCLUSIONS: For most asthma outcomes, ICS at 400 mcg/day of beclomethasone-equivalent are more effective than anti-leukotriene agents given in the usual licensed doses. The exact dose-equivalence of anti-leukotriene agents in mcg of ICS remains to be determined.