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Review: Adding antileukotrienes to inhaled corticosteroids reduces exacerbations in symptomatic chronic asthma

P. John Rees, MD
[+] Article, Author, and Disclosure Information

Source of funding: In part, Canadian Cochrane Network.

For correspondence: Dr. F.M. Ducharme, McGill University, Montreal, Quebec, Canada. E-mail Francine.ducharme@muhc.mcgill.ca.

Ann Intern Med. 2002;136(3):99. doi:10.7326/ACPJC-2002-136-3-099
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Question: In patients with chronic asthma, how effective and safe is daily antileukotriene (AL) therapy plus inhaled corticosteroids (ICS) compared with ICS alone?

Data sources: Studies were identified by searching 4 electronic databases up to September 2001; scanning the reference lists of articles and reviews; reviewing meeting abstracts (1998 to 2000); and contacting the international headquarters of AL manufacturers.

Study selection: Studies were selected if they were randomized controlled trials evaluating the effectiveness of AL for ≥ 1 month in patients with asthma who were ≥ 2 years of age.

Data extraction: Data were extracted independently by 2 reviewers on study quality, patient characteristics, intervention type and duration, and main outcome measures.

Main results: 13 trials (12 in adults and 1 in children) were included. Combining data from 2 of the 6 trials in symptomatic patients and after 4 to 16 weeks of treatment showed that the addition of higher-than-licensed AL doses to ICS reduced the risk for exacerbations requiring systemic corticosteroids (Table). The addition of higher-than-licensed doses also led to an improvement in FEV1 (weighted mean difference [WMD] 0.10 L, 95% CI 0.01 to 0.20), peak expiratory flow rate (WMD 27.2 L/min, CI 18.6 to 35.8), asthma symptom scores (standardized mean difference [SMD] −0.46, CI −0.25 to −0.66), and mean use of β2-agonists (SMD −0.43 puffs/d, CI −0.22 to −0.63). The groups did not differ for any other outcomes. The addition of licensed doses led to nonstatistically significant reductions in the risk for exacerbations requiring systemic steroids (relative risk reduction 39%, CI −5% to 64%).2 trials that compared ICS plus AL at higher-than-licensed doses with double-dose ICS in symptomatic patients showed no differences between groups for the number of exacerbations requiring systemic steroids or for any other outcome. 4 trials that compared AL (at licensed doses) plus ICS with the same dose of ICS in well-controlled patients showed no difference in reduction in ICS dose after 12 to 20 weeks and no difference in the lowest tolerated dose of ICS.

Conclusions: In patients with chronic asthma who are symptomatic while receiving moderate-to-high doses of inhaled beclomethasone, the addition of 2 to 4 times the licensed dose of antileukotriene (AL) agents reduces the rate of exacerbations that require systemic corticosteroids. Insufficient evidence exists that AL confers benefit over doubling the dose of corticosteroids or that it has an inhaled corticosteroid-sparing effect.

Antileukotriene (AL) agents (higher-than-licensed dose) plus inhaled corticosteroids (ICS) vs ICS alone for symptomatic chronic asthma at 4 to 16 weeks*

OutcomeAL + ICSICSRRR (95% CI)NNT (CI)
Exacerbations2%7%66% (12 to 87)22 (12 to 125)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.





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