Does zafirlukast reduce future risk of asthma exacerbations in adults? Systematic review and meta-analysis

Background and objective: The purpose of asthma management is to achieve a total asthma control that involves current control and future risk. It has proven efficacy in reducing asthma exacerbations, but the effect size of zafirlukast for asthma exacerbations of various severity is not systematically explored. Methods: Randomized controlled trials were searched in PubMed Central, Web of Science, and Embase, where zafirlukast prevented asthma exacerbations in adults. The primary outcome was asthma exacerbations, the secondary outcomes were asthma exacerbations requiring systemic corticosteroids and emergency visits, respectively. Odds ratio (OR) with 95% confidence intervals (CI) were pooled. Results: Twelve trials were identified. As first-line therapy, compared to those having placebo, the patients with chronic asthma receiving zafirlukast experienced statistically lower asthma exacerbations (OR = 0.68, 95% CI = [0.45, 1.00]), but it was not found that zafirlukast was superior to placebo in asthma exacerbations requiring systemic corticosteroids (OR = 0.76, 95% CI = [0.45, 1.29]). Furthermore, zafirlukast was inferior to ICs in asthma exacerbations (OR = 2.11, 95% CI = [1.35, 3.30]) and requiring systemic corticosteroids (OR = 3.71, 95% CI = [1.82, 7.59]). As add-on therapy, zafirlukast was not superior to placebo in asthma exacerbations (OR =0.99, 95% CI = [0.54, 1.81] and requiring emergency visits (OR = 0.72, 95% CI = [0.18, 2.99]). Intriguingly, there was not a significant difference in asthma exacerbations between zafirlukast and ICs (OR = 1.12, 95% CI = [0.53, 2.34]). Conclusions: Our study suggests that zafirlukast, as the first-line therapy, significantly reduces mild to moderate but not severe asthma exacerbations. In the add-on regimen, zafirlukast could not reduce asthma exacerbations, which would perhaps result from small sample size and needs to be further studied.