The single maintenance and reliever therapy (SMART) strategy for treating moderate-to-severe asthma refers to providing a single inhaler containing a combination of a glucocorticoid and a rapid-onset, long-acting β₂-agonist (LABA). That inhaler is used for twice-daily maintenance therapy, and patients can use a short-acting β₂-agonist for reliever therapy as needed.

This approach is now recommended in the National Asthma Education Prevention Program guidelines. However, few studies supporting it have included substantial proportions of Black or Latinx individuals, whose mortality rates from asthma are twice as high as those of white individuals.

Elliot Israel, MD, director of clinical research in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, and colleagues conducted a prospective trial in which Black and Latinx adults with asthma were asked to use an inhaled glucocorticoid whenever they used a quick reliever. In The New England Journal of Medicine, the researchers report that this intervention was associated with improvements in every outcome measure studied.

Methods

The Person Empowered Asthma Relief (PREPARE) trial, conducted at 19 U.S. primary care and specialty clinics, enrolled 1,201 adults, ages 18 to 75 years old, who had moderate-to-severe asthma and self-identified as Black (n=603) or Latinx (n=598). Exclusion criteria were minimized so the trial could approximate real-world practice.

Participants were randomly assigned 1:1 either to continue usual care (which could be changed later) or to the intervention. At the only in-person trial visit, all participants received two metered-dose inhalers. For the intervention group, one inhaler administered 80 mcg of beclomethasone.

Participants were instructed in English or Spanish to take one puff of inhaled glucocorticoid for each puff of a quick-reliever inhaler, or five puffs for each quick-reliever nebulization. They were surveyed monthly for up to 15 months (median, 14.9 months in each group).

Primary Endpoint

The primary endpoint was the annualized rate of severe asthma exacerbations as defined by the American Thoracic Society: those that led to the use of systemic glucocorticoids for ≥3 days or an asthma-related hospitalization. The intervention was associated with a 15% lower risk: the rate was 69% in the intervention group and 82% in the usual care group (HR, 0.85; 95% CI, 0.72–0.999; P=0.048).

This difference was consistent throughout the duration of the trial.

Secondary Endpoint

The intervention was also associated with reductions in asthma symptoms and the number of days of impairment:

• Asthma Control Test (scores of 5–25, with lower scores indicating less control; minimal clinically important difference, 3 points)—an increase of 3.4 points in the intervention group vs. 2.5 points in the usual care group (difference, 0.9 points)

• Asthma Symptom Utility Index (scores of 0–1, with lower scores indicating greater impairment; minimal clinically important difference, 0.9 points)—an increase of 0.12 vs. 0.08 points (difference, 0.04 points)

• Annualized number of days of missed work, school, and other usual activities—13.4 vs. 16.8 (rate ratio, 0.80)

Post Hoc Analyses

The clinical benefits of the intervention were accompanied by an 18% lower incidence of β₂-agonist quick-reliever inhaler refills and 32% fewer months of quick-reliever nebulizer use compared with usual care. Those findings are important because quick-reliever therapy is associated with increased mortality in patients with asthma.

Participants in the intervention group used only 1.1 extra glucocorticoid-containing inhaler per year compared with the usual care group.

Putting the Results in Context

The SMART strategy potentially simplifies a patient’s regimen since it requires only one inhaler for maintenance and reliever therapy. However, there are multiple barriers to implementing it:

• The FDA has cautioned against the as-needed use of a combination inhaled glucocorticoid plus LABA

• Many patients “believe in” nebulized quick-reliever therapy or prefer to use it (in this study, the average frequency of use at baseline was 2.9 times per week)

• Not all health insurance policies cover the SMART strategy

Efforts to reduce the burden of asthma for Black and Latinx patients have been labor-intensive, expensive, and variably effective. In this trial, the improvements in outcomes came after only a single visit and appeared to be durable.