Does the Risk of Asthma-Related Events Go Up with Salmeterol +Fluticasone vs. Fluticasone Alone?

For patients with moderate-to-severe asthma and a history of exacerbation, the risk of serious asthma-related events occurred with similar frequency in those who received the combination of long-acting beta-agonist (LABA) salmeterol + the inhaled glucocorticoid, fluticasone propionate and those who received fluticasone alone. However, compared to fluticasone alone, the combination did significantly lower the risk of severe asthma exacerbation. The findings come from a new study published in The New England Journal of Medicine.

A total of 11,679 patients with at least a 1 year history of asthma were enrolled in the trial. They were randomized into 6 separate groups and received the pre-designated treatments for a total of 26 weeks. Three of the groups were administered the fluticasone propionate and salmeterol combination at doses of fluticasone propionate 100μg and salmeterol  50μg, 250μg and 50μg respectively, and 500μg and 50μg, respectively. The remaining 3 groups received fluticasone propionate alone at a doses of 100μg, 250μg or 500μg.

The study’s primary safety end point was the first serious asthma-related event, while the efficacy end point was the first severe asthma exacerbation, defined as asthma deterioration that led to the use of systemic glucocorticoids for at least 3 days.

The number of serious adverse events between the two separate treatments was not significantly different; 34 patients in the fluticasone–salmeterol groups had a total of 36 events, while 33 patients in the fluticasone-only group had 38 events. There was also no significant differences in the rates of asthma-related events according to age group (12 to 17 years, 18 to 64 years, and >64 years) or race (white, black, or other).

However, there was a considerably less amount of severe asthma exacerbations in the fluticasone-salmeterol group; 480 of 5834 patients reported exacerbation in the fluticasone-salmeterol group compared to 597 of 5845 patients in the fluticasone-only group. Furthermore, in four prespecified efficacy subgroups which were classified according to the level of asthma control at baseline, the risk of an asthma exacerbation was 16 to 32% lower in the fluticasone–salmeterol group than in the fluticasone-only group.

The authors conclude that “the clinical benefits of fluticasone–salmeterol were significant, with a 21% lower risk of a severe asthma exacerbation among patients who received that therapy than among those who received fluticasone alone.”

For more information visit NEJM.org.