The addition of anti-leukotriene agents to inhaled corticosteroids versus placebo for chronic asthma

Inhaled steroids remain the cornerstone of asthma treatment. Anti-leukotrienes constitute a new class of drugs that can be taken by mouth and do not have the side effects associated with steroids. We looked to see how effective these drugs were when they were added to the treatment of patients who needed steroid inhalers to control their asthma.In asthmatics that are not well controlled on inhaled steroids, the addition of anti-leukotrienes brings modest improvement in asthma control but it remains unclear whether they are as effective as increasing the dose of inhaled steroids. Higher doses of anti-leukotrienes are more effective, but associated with an increased risk of side effect that occurs with these particular drugs. In asthmatics that are well controlled on inhaled steroids, the addition of anti-leukotrienes did not allow a reduction in the amount of inhaled steroid used but they seemed to have a beneficial effect on the asthma control. There are only two studies that have looked at these issues in children; this is insufficient to firmly conclude whether anti-leukotrienes are useful in children.

Authors' conclusions: 

The addition of licensed doses of anti-leukotrienes to add-on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti-leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. 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.

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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 August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003).

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 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full-text and 16 trials reported data in a way that allowed meta-analysis. 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) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short-acting beta2-agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti-leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS-sparing studies of patients who were well controlled at baseline, addition of anti-leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD -21 mcg/d, 95%CI -65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95).

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