Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma

Patients who continue to experience asthma symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Leukotriene receptor antagonists (LTRA) and long-acting beta(2)-agonists (LABA) agents may both be considered as add-on therapy to inhaled corticosteroids (ICS). We compared the efficacy and safety profile of adding either daily LABA or LTRA in asthmatic patients who remained symptomatic on ICS. The Cochrane Airways Group Specialised Register was searched for randomised controlled trials up to and including March 2006. Reference lists of all included studies and reviews were screened to identify potentially relevant citations. Inquiries regarding other published or unpublished studies supported by the authors of the included studies or pharmaceutical companies who manufacture these agents were made. Conference proceedings of major respiratory meetings were also searched. Only randomised controlled trials conducted in adults or children with recurrent asthma where a LABA (for example, salmeterol or formoterol) or LTRA (for example, montelukast, pranlukast, zafirlukast) was added to ICS for a minimum of 28 days were considered for inclusion. Inhaled short-acting beta(2)-agonists and short courses of oral steroids were permitted as rescue medications. Other daily asthma treatments were permitted, providing the dose remained constant during the intervention period. Two reviewers independently reviewed the literature searches. Data extraction and trial quality assessment were conducted independently by two reviewers. Whenever possible, primary study authors were requested to confirm methodology and data extraction and to provide additional information and clarification when needed. Where necessary, expansion of graphic reproductions and estimation from other data presented in the paper was performed. Fifteen randomised controlled trials met the inclusion criteria; eleven trials including 6,030 participants provided data in sufficient detail to permit aggregation. All eleven trials pertained to adults with moderate airway obstruction (% predicted FEV(1) 66-76%) at baseline. Montelukast (n=9) or Zafirlukast (n=2) was compared to Salmeterol (n=9) or Formoterol (n=2) as add-on therapy to 400-565 mcg of beclomethasone or equivalent. Risk of exacerbations requiring systemic corticosteroids was significantly lower with LABA+ICS when compared to LTRA+ICS (RR= 0.83, 95% Confidence Interval (95%CI): 0.71, 0.97): the number needed to t