Denver, CO—Growing evidence suggests that response to medication therapy by individuals or specific cohorts varies much more than previously expected. One example is a new study of African Americans with poorly controlled asthma, which found wide differences in patients’ responses to commonly used treatments.

The article published in the New England Journal of Medicine reports that, much to the surprise of researchers, nearly half of the young children in the study had responses to asthma treatment dissimilar to older children and adults—and also to white children, as documented in previous studies.

“We shouldn’t assume that current treatment strategies for asthma are ideal for all African Americans since for many years that population was not adequately represented in research,” explained senior author Elliot Israel, director of clinical research in the Pulmonary and Critical Care Medicine Division at Brigham and Women’s Hospital. “We found that almost half of the African American children studied responded better to increasing the dose of inhaled corticosteroids than adding a long-acting bronchodilator. Thus, adding a long-acting bronchodilator may not be the right answer for nearly half of African American children.”

Background information in the report notes that morbidity from asthma is disproportionately higher among black patients than among white patients, yet black patients constitute the minority of participants in trials informing treatment.

The study team points out that past research has indicated that patients with inadequately controlled asthma benefit more from the addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids. They caution, however, that the guidance may not be applicable to treating some black patients.

To try to determine that, researchers conducted two prospective, randomized, double-blind trials with a total of 574 patients. One involved children, while the other included adolescents and adults. In both trials, participants had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids.

Combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double-to-quintuple the dose of fluticasone, or both, were compared in the trials. 

Effects of the therapies were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

Results indicate that, when five times the dose of fluticasone (to 250 mcg twice a day) was compared with adding salmeterol (50 mcg twice a day) and twice the fluticasone (to 100 mcg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = .99).

On the other hand, researchers found that more adolescents and adults had a better response to added salmeterol than to an increase in fluticasone (salmeterol–low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = .003]; salmeterol–medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = .02]).

“Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments,” the study points out. “The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.”

“This study suggests that we cannot look at results from one population and extrapolate the findings to African Americans or any other group,” explained principal investigator Michael Wechsler, MD, professor of medicine at National Jewish Health in Denver. “If children do not respond to one treatment, parents and providers could consider another option because there is almost a 50% chance of having a better response.”

“Although we cannot attribute the study’s findings to genetic markers of African ancestry, there could be as-yet unknown genetic variants specific to people of African descent that affect how severe a patient’s asthma is,” Dr. Wechsler said.

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