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


OBJECTIVE
We compared the efficacy and safety profile of adding either daily LABA or LTRA in asthmatic patients who remained symptomatic on ICS.


METHODS
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 Inquiries regarding other published or unpublished studies supported by the authors of the included studies or pharmaceutical companies who manufacture these agents were made.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.


METHODS
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.


METHODS
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.


RESULTS
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 treat with LABA compared to LTRA, to prevent one exacerbation over 48 weeks, was 38 (95% CI: 23 to 247). The following outcomes also improved significantly with the addition of LABA compared to LTRA to inhaled steroids (Weighted Mean Difference; 95%CI): morning PEFR (16 L/min; 13 to 18), evening PEFR (12 L/min; 9 to 15), FEV(1) (80 mL; 60 to 100), rescue-free days (9%; 5% to 13%), symptom-free days (6%; 2 to 11), rescue beta(2)-agonists (-0.5 puffs/day; -0.2 to -1), quality of life (0.1; 0.05 to 0.2), symptom score (Standard Mean Difference -0.2; -0.1 to -0.3), night awakenings (-0.1/week; -0.06 to -0.2) and patient satisfaction (RR 1.12; 1.07 to 1.16). Risk of withdrawals due to any reason was significantly lower with LABA+ICS compared to LTRA+ICS (Risk Ratio 0.83, 95% CI 0.73 to 0.95). Withdrawals due to adverse events or due to poor asthma control, hospitalisation, osteopenia, serious adverse events, overall adverse events, headache or cardiovascular events were not significantly different between the two study groups.


CONCLUSIONS
In asthmatic adults inadequately controlled on low doses of inhaled steroids, the addition of LABA is superior to LTRA for preventing exacerbations requiring systemic steroids, and for improving lung function, symptoms, and the use of rescue beta(2)-agonists.
Ducharme
F M
FM
The Montreal Children's Hospital, Rm C-538E, 2300 Tupper Street, Montreal, Quebec, Canada. francine.ducharme@muhc.mcgill.ca
Lasserson
T J
TJ
Cates
C J
CJ
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D020024:Leukotriene Antagonists