The safety of long-acting beta-agonists (LABAs) such as salmeterol and formoterol, in medications such as Advair, Symbicort, Dulera, and Breo, has been widely debated. Large, poorly structured trials in the past have shown increased risk of serious asthma related events in patients on LABAs, but many patients were on these without adequate asthma controller medication.

A new study published in the New England Journal of Medicine (May 12 2016) addresses this issue. A multicenter, randomized, double-blind trial of adolescent and adult patients with persistent asthma randomized patients to either fluticasone with salmeterol or fluticasone alone for 26 weeks. All patients had a history of a serious asthma exacerbation in the year before study onset, though not the previous month. Patients were excluded if they had life threatening or unstable asthma. The primary end point was the first series asthma related event (death, incubation, or hospitalization.)

Of 11,679 patients enrolled, 67 had 74 serious asthma related events, with similar numbers in both groups and no statistically significant different between them. There were no asthma related deaths, and only 2 intubations, both in the fluticasone group. The risk of asthma exacerbation was 21% lower in the fluticasone-salmeterol group vs. the fluticasone only group.

The conclusions of the study were that salmeterol in fixed dose combination with fluticasone did not lead to a significantly higher risk of serious asthma-related events, and patients on fluticasone-salmeterol combination therapy had fewer severe asthma exacerbations than the fluticasone only group.

(N Engl J Med 2016;374:1822-30)

Dr. Kenneth Backman of Allergy & Asthma Care of Fairfield County comments: “There has been concern about the safety of LABAs since a couple of poorly designed studies over a decade ago. Several smaller studies have shown no danger of LABAs when combined with inhaled corticosteroid, but this large, very well designed study is the most reassuring so far that inhaled steroid-LABA combination therapy is safe and puts asthma patients at no increased risk of exacerbations or adverse effects. In fact, the combination therapy actually reduced the risk of exacerbations. There is still a need for further studies, because this study did not include children under 12, and excluded patients with very severe, life-threatening asthma.”