Effectiveness of drug treatment strategies to prevent asthma exacerbations and increase symptom-free days in asthmatic children: a network meta-analysis.

OBJECTIVE: To determine the effectiveness and safety of current maintenance therapies that include inhaled corticosteroids (ICS), long-acting β-agonists (LABA) and/or leukotriene receptor antagonists (LTRAs) in preventing exacerbations and improving symptoms in pediatric asthma.

METHODS: A systematic review with network meta-analysis was conducted after a comprehensive search for relevant studies in the PubMed, Cochrane Library, Embase and Clinical Trials databases, up to July 2014. Randomized clinical trials were selected comparing treatment strategies of the Global Initiative for Asthma guidelines. The full-text randomized clinical trials compared maintenance treatments for asthma in children (≤18 years) of ≥4 weeks duration, reporting exacerbations or symptom-free days. The primary and secondary effectiveness outcomes were the rates of moderate/severe exacerbations and symptom-free days from baseline, respectively. Withdrawal rates were taken as the safety outcome.

RESULTS: Included in the network meta-analysis was 35 trials, comprising 12,010 patients. For both primary and secondary outcomes, combined ICS and LABA was ranked first in effectiveness (OR 0.70, 95% CI: 0.52-0.97 and OR 1.23, 95% CI: 0.94-1.61, respectively, compared with low-dose ICS), but the result of secondary outcomes was statistically insignificant. Low-dose ICS, medium- or high-dose ICS and combined ICS and LTRA strategies were comparable in effectiveness. ICS monotherapies, and ICS + LABA and ICS + LTRA strategies were similarly safe. High-dose ICS had the highest rate of total withdrawals, but the difference was not significant.

CONCLUSIONS: Combined ICS and LABA treatments were most effective in preventing exacerbations among pediatric asthma patients. Medium- or high-dose ICS, combined ICS and LTRAs, and low-dose ICS treatments seem to be equally effective.