Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma
Ducharme F, Hicks G, Kakuma R (Cochrane Review). In: The Cochrane Library, Issue 2, 2002. Oxford: Update Software.

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 ATS meeting abstracts (1998-2000).
Selection criteria: Randomised placebo-controlled trials of asthmatics aged 2 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 1 paediatric) trials met inclusion criteria. Seven were published in full-text. In sympomatic 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) 0.36,1.05). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.71 L/min; 95%CI 2.98, 12.44 L/min) together with beta2-agonist use (WMD= -0.32 puffs/day; 95%CI -0.0.08, -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, 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 may be associated with superior asthma control after glucocorticoid tapering, but a glucocorticoid-sparing effect cannot be quantified at present.

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