Compared with black adolescents and adults, nearly half of all black children with poorly controlled asthma exhibit a superior response to an escalation in the dose of an inhaled glucocorticoid, and nearly half had a superior response to the addition of the long-acting beta agonist salmeterol. Two parallel, prospective, randomized, double-blind trials (Best African American Response to Asthma Drugs [BARD;ClinicalTrials.gov identifier: NCT01967173]) were conducted to determine the preferred “step-up” therapeutic strategy in children, adolescents, and adults with at least 1 grandparent who identified as black. Results of the analysis were published in the New England Journal of Medicine.
In addition to establishing the ideal step-up therapy among those being evaluated, the investigators further examined the extent to which biomarkers, patient characteristics, and ancestral informative genomic variation predicted response to treatment with inhaled glucocorticoids or long-acting beta agonists. In both BARD trials, all the patients had at least 1 grandparent who identified himself or herself as being black and had asthma that was inadequately controlled with the use of low-dose inhaled glucocorticoids. Of the 2 BARD studies, 1 evaluated children and the other evaluated adolescents and adults.
The 2 trials explored combinations of therapy. In the study that involved children, the researchers compared the efficacy of several treatment regimens: doubling the dose of the inhaled glucocorticoid fluticasone propionate to a dose of 100 µg, administered twice daily (the double-fluticasone group); doubling the dose of fluticasone to 100 µg and adding the long-acting beta agonist salmeterol at a dose of 50 µg (the salmeterol-double-fluticasone group); quintupling the dose of fluticasone to 250 µg (the quintuple-fluticasone group); or quintupling the dose of fluticasone to 250 µg and adding salmeterol at a dose of 50 µg (the salmeterol-quintuple-fluticasone group).
In the trial that involved adolescents and adults, the investigators compared the efficacy of the following treatment regimens: adding twice-daily salmeterol at a dose of 50 µg to baseline twice-daily fluticasone propionate at a dose of 100 µg (the salmeterol-fluticasone group), increasing the dose of fluticasone by a factor of 2.5 to 250 µg (the 2.5-fluticasone group), quintupling the dose of fluticasone to 500 µg (the quintuple-fluticasone group), or increasing the dose of fluticasone by a factor of 2.5 to 250 µg and adding salmeterol at a dose of 50 µg (the salmeterol-2.5-fluticasone group).
In both studies, all the treatments were compared with the use of a composite measure that assessed asthma exacerbations, asthma-control days, and pulmonary function. All data were stratified according to genotypic African ancestry. The primary aims of the studies were to evaluate the superiority of the different treatment regimens and the effect of the proportion of African ancestry on the composite clinical outcome.
From January 2014 through March 2016, a total of 280 children and 294 adolescents and adults underwent randomization at 9 centers. Among the children, the majority were boys. In contrast, the majority of the adolescents and adults were women. More children, compared with adolescents/adults, had blood eosinophil counts of ≥300 cells/mm3.
Results of the study showed that when treatment with the quintupled dose of fluticasone (to 250 µg twice daily) was compared with the addition of salmeterol (50 µg twice daily) and with the doubled dose of fluticasone (to 100 µg twice daily), a superior response was reported in 46% of the children with the quintupled dose of fluticasone, as well as in 46% of the children with the doubled fluticasone dose and the addition of salmeterol (P =.99).
In addition, more adolescents and adults exhibited a significantly superior response to the addition of salmeterol than to an escalation in the fluticasone dose (49% in the salmeterol-fluticasone group vs 28% in the 2.5-fluticasone group [P =.003]; 49% in the salmeterol-2.5-fluticasone group vs 31% in the quintuple-fluticasone group [P =.02]). The differences in superior response rates were driven by differences in asthma-control days and forced expiratory volume in 1 second. The degree of African ancestry and baseline biomarkers were not predictive of a superior response to specific treatments.
The investigators concluded that a larger, more simplified study is warranted to establish the best therapeutic approach for black children with poorly controlled asthma despite the use of a standard dose inhaled glucocorticoid.
Wechsler ME, Szefler SJ, Ortega VE, et al; NHLBI AsthmaNet. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med. 2019;381(13):1227-1239.