Effect of leukotriene receptor antagonist therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials

Background-Asthma exacerbations contribute substantially to morbidity, and their reduction is an important therapeutic objective. In this integrated a nalysis the risk of asthma exacerbations was assessed during treatment with the leukotriene receptor antagonist zafirlukast. Methods-Data were collected from all five double blind, multicentre, random ised, placebo controlled, 13 week trials of zafirlukast 20 mg twice daily p erformed in steroid-naive patients with mild to moderate asthma. Exacerbati on data were collected prospectively during monitoring of adverse events an d concomitant medication use. Pooled data were used to assess the relative risk of asthma exacerbations using three definitions: worsening of asthma l eading to withdrawal from the study; requirement for additional antiasthma therapy (excluding increased short acting beta(2) agonist use); and require ment for oral corticosteroid therapy. Results-The proportion of patients with an asthma exacerbation leading to w ithdrawal was consistently lower in the group treated with zafirlukast 20 m g twice daily than in the placebo group. Overall, the risk of an asthma exa cerbation requiring withdrawal from zafirlukast therapy was approximately h alf that of placebo (odds ratio 0.45; 95% CI 0.26 to 0.76; p = 0.003). Simi lar results were observed for exacerbations requiring additional control me dication (odds ratio = 0.47; 95% CI 0.30 to 0.74; p = 0.001) and oral corti costeroid rescue (odds ratio = 0.53; 95% CI 0.32 to 0.86; p = 0.010). Conclusions-Zafirlukast in a dose of 20 mg twice daily reduces the risk of asthma exacerbations and the need for additional anti-asthma therapies, ful filling an important goal of control medication in patients with mild to mo derate asthma.