The findings of these 2 new studies are in contrast to those of previous trials, which had conflicting results.
The addition of a long-acting Î²-agonist to an inhaled corticosteroid appears to be safe for children and adults who have moderate to severe asthma, according to 2 new studies.
The findings are in contrast to those of previous trials that had conflicting results, which had led the FDA to issue a black-box warning on the safety of long-acting Î²2-agonists. These agents have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children.
Budesonide plus Formoterol vs Budesonide Alone
In an FDA-mandated postmarketing safety study, researchers led by Stephen P. Peters, MD, PhD, Wake Forest School of Medicine in Winston-Salem, NC, evaluated the increased risk of serious asthma-related events in patients who have asthma with the addition of formoterol to budesonide maintenance therapy.
The multicenter, double-blind, 26-week study randomly assigned 11,693 patients, age 12 years and older, to receive budesonide–formoterol (5846 patients) or budesonide alone (5847 patients). The patients had persistent asthma, were receiving daily asthma medication, and had had 1 to 4 asthma exacerbations in the previous year.
A serious asthma-related event occurred in 43 patients who were receiving budesonide–formoterol and in 40 patients who were receiving budesonide. “The budesonide–formoterol was shown to be non-inferior to budesonide alone,” the researchers stated.
There were 2 asthma-related deaths, both in the budesonide–formoterol group. One of the patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide–formoterol than with budesonide.
The researchers concluded: “Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide–formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events.”
Adding Salmeterol to Fluticasone Propionate
In the second study, researchers led by David A. Stempel, MD, of the Respiratory Clinical Development department at GlaxoSmithKline, randomly assigned 6208 patients to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The patients were children age 4 to 11 years who required daily asthma medications and had a history of asthma exacerbations in the previous year.
A serious asthma-related event occurred in 27 patients in the fluticasone–salmeterol group and 21 patients in the fluticasone-alone group; all were hospitalized. “The hazard ratio with fluticasone–salmeterol versus fluticasone alone was 1.28, which showed the non-inferiority of fluticasone–salmeterol,” the researchers stated.
A total of 265 patients (8.5%) in the fluticasone–salmeterol group and 309 (10%) in the fluticasone-alone group had a severe asthma exacerbation. No patients died in either treatment group.
The researchers concluded: “In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone.”
The results of these 2 studies should help assuage concerns that remain about the safety of adding long-acting Î²2-agonists to inhaled glucocorticoids for the treatment of asthma.
The results of both trials were published online August 31, 2016 in the New England Journal of Medicine.