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.

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

BACKGROUND: Inhaled corticosteroids are the cornerstone of anti-inflammatory asthma treatment. Anti-leukotrienes agents are currently being studied as alternative first line agents in the management of mild to moderate chronic asthma. OBJECTIVES: The aims of this review study are to compare the safety and efficacy of anti-leukotriene agents with inhaled glucocorticoids and to determine the dose-equivalence of anti-leukotrienes in mcg of inhaled corticosteroids in the management of chronic asthma. SEARCH STRATEGY: The searched Medline (1966 to 1999), Embase (1980 to 1999), Cinahl (1982 to 1999) and reference lists of review articles and trials; we contacted colleagues and international headquarters of anti-leukotrienes producers. SELECTION CRITERIA: Randomised controlled trials were included if they compared leukotriene antagonists with inhaled corticosteroids during a minimal 30-day intervention period in asthmatic patients aged 2 years and older, and if measures of effectiveness other than compliance were included. DATA COLLECTION AND ANALYSIS: Assessments of methodological quality and data extraction were performed independently and blindly by two reviewers. 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: Of 137 identified studies, ten met the inclusion criteria. Two are currently published in full-text. Most focused on subjects with mild-to-moderate chronic asthma; two included children. Trial duration was 6 to 12 weeks with a few un-blinded trials lasting several months. Daily dose of inhaled corticosteroids varied from 250 to 400 mcg of beclomethasone-equivalent; various anti-leukotriene preparation were tested. There was no difference in the rate of patients with exacerbations that required systemic steroids [4 trials, Relative Risk (RR)=1.3, (95% Confidence Interval (CI): 0.9, 1.9)]. Few trials contributed data to other outcomes. Improvement in lung function (FEV1 [N=3 trials, Standardised Mean Difference (SMD)=0.3 (95% CI: 0. 2, 0.4)]: morning PEFR [3 trials, SMD=0.4, (95% CI: 0.2, 0.5)]) and in quality of life [N=3 trials, WMD=0.3, (95% CI: 0.1, 0.4)] favoured inhaled corticosteroids. A difference in favour of inhaled corticosteroids was observed for symptoms [N=3 trials, SMD=0.3, (95% CI: = 0.2, 0.4)], night awakenings [N=2 trials, WMD= 0.6, (95% CI: 0. 3, 0.9)], and rescue beta2-agonists [N=3 trials, SMD= 0.3, (95% CI: 0.2, 0.4)] Side effects were not different between groups, but anti-leukotriene therapy was associated with increase risk of "withdrawals for any cause" [N=3 trials, RR=1.4, (95% CI: 1.1, 1.9)] and "withdrawals due to adverse effects" [N=3 trials, RR=1.9, (95% CI: 1.1, 3.3)] REVIEWER'S CONCLUSIONS: Anti-leukotriene agents had a similar rate of exacerbations compared to inhaled corticosteroids, but inhaled steroids produced better lung function and quality of life as well as reduced symptoms, night awakenings and need for rescue beta2-agonist. Reliable conclusions cannot yet be drawn regarding the efficacy of this treatment due to the paucity of trials published in full text.