Leukotriene-Receptor Antagonists Improve Asthma Control

Laurie Barclay, MD

September 21, 2015

Orally administered leukotriene-receptor antagonists (LRTAs), alone or with inhaled corticosteroids (ICSs), significantly improved asthma control and reduced exacerbations, according to a systematic review published online September 22 in the Annals of Internal Medicine. Adverse events were similar in the LTRA and placebo groups.

"Successful long-term management of asthma includes the use of medications that target the underlying inflammatory process," Michael Miligkos, MD, from the University of Thessaly School of Medicine in Larissa, Greece, and colleagues write. "Although [ICSs] constitute the current gold standard of maintenance treatment, [LTRAs] have the advantages of oral once- or twice-daily dosing and apparent avoidance of the adverse effects associated with long-term corticosteroid therapy."

Because the effect of LTRAs compared with placebo is still unclear, the investigators aimed to evaluate the benefits and harms of LTRAs as monotherapy or in combination with ICSs compared with placebo in adults and adolescents with asthma.

A search of MEDLINE and the Cochrane Central Register of Controlled Trials through June 2015 identified 2008 pertinent abstracts for screening. Fifty trials met eligibility criteria and were peer-reviewed, English-language, randomized controlled trials in patients with asthma comparing the effect of LTRAs with that of placebo on measures of asthma control.

Three investigators extracted data regarding study population, interventions, outcome measures, and adverse events, whereas one investigator determined risk for bias.

LTRAs cut the risk for an exacerbation by 40% compared with placebo (summary risk ratio [RR], 0.60; 95% confidence interval [CI], 0.44 - 0.81), based on random-effects meta-analyses of six trials of LTRA monotherapy. Reduction in risk for an exacerbation was 20% in four trials of LTRAs as add-on therapy to ICSs (summary RR, 0.80; 95% CI, 0.60 - 1.07).

When used either as monotherapy or add-on therapy to ICSs, LTRAs increased forced expiratory volume in 1 second compared with placebo. However, LTRAs were associated with improved forced expiratory volume in 1 second percentage of predicted values only in trials of LTRA monotherapy.

LTRA and placebo groups had similar adverse event rates and withdrawals resulting from adverse events and worsening asthma, indicating a favorable safety and tolerability profile for LTRAs.

Limitations of this systematic review and meta-analysis were variation in outcomes definitions and reporting, high risk for bias in some studies, heterogeneity of findings, possible selective outcome reporting bias, and inability to determine the effect of asthma severity on summary estimates.

On the basis of their findings, the investigators conclude that LTRAs as monotherapy improved asthma control compared with placebo, and that the effect was consistent across all types of LTRAs. Only some measures of asthma control were significantly improved in trials of LTRAs used as add-on therapy to ICSs.

"Our findings suggest that LTRAs may be efficacious and safe, either as an alternative treatment in adult and adolescent patients who cannot or prefer not to take ICSs or as add-on treatment in patients with concomitant ICS use," the review authors conclude. "However, which patients are more likely to respond to LTRAs remains unclear."

The National Institutes of Health funded this study. One coauthor reports receiving grants from the Agency for Healthcare Research and Quality outside the scope of this review. The other authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online September 22, 2015.


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