MONTREAL—Should leukotriene receptor antagonists be considered as alternatives to inhaled corticosteroids for mild asthma monotherapy, as some guidelines recommend? Apparently not, suggest the findings of a recent analysis by Francine M. Ducharme, MD, from McGill University Health Centre in Montreal.[1]

After analyzing 13 trials that compared the two treatments in patients with mild or moderate persistent asthma, Dr. Ducharme, an Associate Professor of Pediatrics and Epidemiology, found that patients given leukotriene receptor antagonists were 60% more likely to suffer exacerbations requiring systemic glucocorticoids. They also had poorer lung function and more frequent problems with asthma symptoms than did the inhaled corticosteroid recipients.

“These findings were so robust that 59 new trials showing no difference between the two drugs would be necessary to nullify the findings,” estimated Dr. Ducharme. It is therefore safe, she said, to conclude that low-dose inhaled glucocorticoids are more effective than leukotriene receptor antagonists for mild and moderate persistent asthma.

To identify trials for her analysis, Dr. Ducharme searched the MEDLINE, Embase, CINAHL, and Cochrane databases; she also checked the reference lists in the papers she found and contacted pharmaceutical companies producing antileukotrienes and inhaled corticosteroids to identify unpublished studies. Only randomized controlled trials that compared at least 28 days of therapy with leukotriene receptor antagonists or stable doses of inhaled corticosteroids were eligible for review.

Of the 13 trials that were included, 10 were of high methodologic quality; five were new investigations completed since the previous review of this topic. Four of the trials addressed mild asthma, and eight looked at moderate asthma; the severity of asthma was not reported in one trial. Only one study included children.

The trials typically compared montelukast (10 mg/d) or zafirlukast (20 mg twice daily) to low doses of inhaled beclomethasone or fluticasone (the corticosteroid doses were usually equal to 400 µg of chlorofluorocarbon-propelled beclomethasone). Results favoring corticosteroids were similar regardless of which leukotriene receptor antagonist was used; any heterogeneity between trial results was not attributable to the choice of agent, Dr. Ducharme noted.

Compared with the patients who received inhaled corticosteroids, those treated with leukotriene receptor antagonists had a relative risk of 1.6 for moderate asthma exacerbations. Moreover, inhaled corticosteroids produced a 130-mL larger mean increase in forced expiratory volume in one second than did the other drugs. Corticosteroid use also resulted in a greater improvement in morning peak flow, a steeper drop in rescue ß2-agonist use, and greater declines in the number of asthma symptoms and nocturnal awakenings.

There was no difference between the inhaled corticosteroid and leukotriene receptor antagonist groups in the rate of adverse effects, such as headache, oral candidiasis, nausea, increased liver enzyme test results, and death. However, the likelihood of patients withdrawing from a trial because of poor asthma control was greater with the leukotriene receptor antagonists.

Because the analysis included only one pediatric trial, the findings need to be replicated in children. “The only other burning question is whether antileukotrienes are better than long-acting ß2-agonists as add-on therapy for asthma patients who are already taking inhaled glucocorticoids,” Dr. Ducharme related.

—Timothy Begany