Optimal step-up therapy for black children and adults with poorly controlled asthma

Reference

Wechsler ME, Szefler SJ, Ortega VE, et al, for the NHLBI AsthmaNet. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med 2019;381(13):1227-1239.

Synopsis

There have been signals in previous trials that black and African-American persons may respond differently to step-up therapy for poorly controlled asthma than white patients. This report describes the results of 2 randomized controlled trials, one in black children ages 5 years to 11 years and one in black adults and adolescents 12 years and older. All had asthma that was inadequately controlled while taking a low-dose ICS, defined as fluticasone 50 mcg twice daily in children and fluticasone 100 mcg twice daily in adolescents and adults. After a run-in period of low-dose ICS to confirm poor asthma control, the patients were randomized to one of the step-up therapies and followed up for 1 year. There were 4 step-up options for children: (1) doubling fluticasone to 100 mcg twice daily, (2) doubling fluticasone to 100 mcg twice daily and adding salmeterol 50 mcg twice daily, (3) quintupling the fluticasone dose to 250 mcg twice daily, or (4) quintupling the fluticasone to 250 mcg twice daily and adding salmeterol 50 mcg twice daily. For adolescents and adults, the 4 step-up regimens were (1) adding salmeterol 50 mcg twice daily to fluticasone 100 mcg twice daily, (2) increasing the fluticasone dose from 100 to 250 mcg twice daily, (3) quintupling the fluticasone dose to 500 mcg twice daily, or (4) increasing the fluticasone dose to 250 mcg twice daily and adding salmeterol 50 mcg twice daily. The researchers defined black or African-American as having at least one grandparent who identified as black. The average age of the children was 8.5 years and the avergae age of adults was 37.3 years, and in both groups the median percentage of African ancestry was 81%. A total of 74% of children and 45% of adults had an unscheduled office or emergency department visit in the past 12 months. This was a crossover study, with each patient using one of the step-up therapies during four 14-week treatment periods, each of which included an initial 2-week washout period. The primary outcome was response to therapy, defined using a sequential combination of exacerbations, asthma control days, and FEV1. In children, quintupling the ICS dose was as likely to improve the primary outcome as doubling the ICS dose and adding salmeterol. In adolescents and adults, though, adding salmeterol to a low or medium dose of ICS was better than medium- or high-dose ICS alone (49% vs 28%; P = .003; number needed to treat [NNT] = 5 for the comparison of salmeterol/low-dose fluticasone with medium-dose fluticasone, and 49% vs 31%; P = .02; NNT = 5 for the comparison of salmeterol/medium-dose fluticasone with high-dose fluticasone).