Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma (Cochrane Review)

A substantive amendment to this systematic review was last made on 25 October 2001. Cochrane reviews are regularly checked and updated if necessary.

Background: Anti-leukotriene (AL) agents are being considered as 'add-on' therapy to inhaled corticosteroids (ICS), in chronic asthma.

Objectives: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma.

Search strategy: We searched MEDLINE, EMBASE, CINAHL (until September 2001), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society meeting abstracts (1998 to 2000).

Selection criteria: Randomised placebo-controlled trials of asthmatics aged two years and older with at least one month intervention.

Data collection and analysis: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double).

Main results: Of 438 citations, 13 (12 adult and one paediatric) trials met inclusion criteria. Seven were published in full-text. In symptomatic patients, addition of licensed doses of anti-leukotrienes to ICS resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.61; 95% Confidence Interval (CI) 0.36 to 1.05). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.71 L/min; 95% CI 2.98 to 12.44 L/min) together with beta-2-agonist use (WMD -0.32 puffs/day; 95%CI -0.08 to -0.56). No trials that compared the use of licensed doses of anti-leukotrienes with doubling-dose of inhaled glucocorticoids could be pooled. In ICS-sparing studies in patients who were well controlled at baseline, addition of anti-leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD -44.4 mcg/d, 95%CI -147.9, 59.0 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.56, 95%CI 0.35 to 0.89).

Reviewers' conclusions: There is insufficient evidence to firmly support the use of licensed doses of anti-leukotrienes as add-on therapy to inhaled glucocorticoids. Addition of anti-leukotrienes to inhaled glucocorticoids may slightly improve asthma control, but the available data do not permit this strategy to be recommended as a substitute for increasing the dose of inhaled glucocorticoids. Addition of anti-leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid-sparing effect cannot be quantified at present, it appears modest.

Citation: Ducharme F, Hicks G, Kakuma R. Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.

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This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

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