Leukotriene-receptor antagonists associated with reduced risk of asthma exacerbations

1. From a systematic review, the use of leukotriene receptor antagonists (LTRAs) as monotherapy was associated with a decreased risk of asthma exacerbations when compared to placebo.

2. Use of LTRAs in combination with inhaled corticosteroids may have also reduced risk of asthma exacerbation and improved lung function when compared to placebo, although results were mixed.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Asthma affects approximately 300 million people worldwide. Long-term control of asthma is directed at reducing the inflammatory processes that underlie the disease. Leukotriene-receptor antagonists (LTRAs) target these inflammatory processes, and have a number of potential advantages compared to steroids. This study summarized and analyzed several trials comparing LTRAs versus placebo and LTRAs in combination with steroids. When used alone, LTRAs significantly reduced the risk of asthma exacerbations and improved lung function when compared to placebo. When combined with steroids, use of LTRAs was associated with improvement in lung function by some measures, although not with decreased risk of asthma exacerbations. Notably, LTRAs were not associated with increased risk of adverse effects compared to placebo. This study analyzed a diverse set of trials, and was limited by the varied set of outcome measures and treatments used in these trials; this particularly hampered the study from assessing the effect of asthma severity on outcomes. Nevertheless, these results suggest that LTRAs may be effective alternatives to steroids as therapy designed to prevent asthma exacerbations, and that these drugs may also be valuable as add-on therapy for patients already taking steroids.

Click to read the study published today in the Annals of Internal Medicine

Relevant Reading: Guidelines for the Diagnosis and Management of Asthma (EPR-3)

In-Depth [systematic review and meta-analysis]: This systematic review and meta-analysis synthesized results from 50 studies that compared LTRAs (i.e., montelukast, zafirlukast or pranlukast) or LTRAs plus inhaled corticosteroids (ICS) with placebo. As monotherapy, LTRAs were associated with a significantly reduced risk of asthma exacerbation (RR compared to placebo 0.60, 95%CI 0.44-0.81), as well as with significantly improved FEV1 compared to baseline FEV1. When used as add-on therapy with ICS, LTRAs did not significantly reduce the risk of asthma exacerbation compared with placebo (RR 0.80, 95%CI 0.60-1.07); as add-on therapy, they did significantly improve FEV1 over baseline when change in FEV1 was expressed in liters, but not when expressed as percent change. Notably, LTRAs significantly reduced the need for short-acting beta agonists in the included trials, both when used as monotherapy and when used as add-on therapy with ICS. Due to heterogeneity of inclusion criteria, study therapies and outcome measures, only a few studies could be analyzed for each of this trial’s outcomes of interest.

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