The fully virtual, decentralized phase IIIb BATURA clinical trial demonstrated that as-needed use of albuterol-budesonide significantly reduced the risk of severe asthma exacerbations compared with albuterol alone in patients with mild, uncontrolled asthma. Specifically, participants who used the combination inhaler had a 47% lower risk of severe exacerbation.
"A severe exacerbation occurred in 5.1% of the participants in the albuterol–budesonide group and in 9.1% of those in the albuterol group in the on-treatment efficacy population (hazard ratio = 0.53, 95% confidence interval [CI] = 0.39-0.73)," the researchers reported.
They stopped the study early at a prespecified interim analysis due to the clear efficacy advantage demonstrated by the combination therapy. The findings extend previous research that showed benefits of combination therapy in moderate-to-severe asthma to patients with milder disease.
In the trial, 2,516 participants aged 12 years or older with uncontrolled asthma despite treatment with either a short-acting β2-agonist (SABA) alone or with a low-dose inhaled glucocorticoid or leukotriene-receptor antagonist were randomized to receive either the combination treatment or albuterol alone for up to 52 weeks.
Beyond the primary endpoint, secondary outcomes also favored the combination therapy. The annualized rate of severe asthma exacerbations was 0.15 in the albuterol-budesonide group vs 0.32 in the albuterol group (rate ratio = 0.47; 95% CI = 0.34-0.64). Additionally, the mean annualized total dose of systemic glucocorticoids was substantially lower with albuterol-budesonide (23.2 vs 61.9 mg per year).
These findings align with current Global Initiative for Asthma (GINA) recommendations, which no longer support SABA-only treatment for mild asthma due to the risks of severe exacerbations even in patients with infrequent symptoms.
"During periods of asthma worsening, patients often rely on their SABA rescue therapy alone, which does not address airway inflammation, thus increasing the risk of severe or fatal exacerbations," the authors explained.
The combination inhaler allows patients to receive an inhaled glucocorticoid simultaneously with their rescue bronchodilator when symptoms appear. This approach targets both bronchoconstriction and underlying inflammation immediately in response to symptoms.
The safety profiles between the two treatment arms showed comparable rates of adverse events (42.2% in the albuterol-budesonide group vs 43.5% in the albuterol group). The most common adverse events were upper respiratory tract infections, COVID-19, and nasopharyngitis.
The BATURA trial represents one of the first fully virtual asthma trials. This decentralized approach facilitated broader recruitment but led to a relatively high loss-to-follow-up rate of approximately 19%.
The researchers acknowledged several limitations, including the small number of adolescent participants (2.8% were 12 to 17 years old), which limits generalizability to younger populations. Additionally, the virtual study design precluded objective lung function measurements or biomarker assessments that might have provided mechanistic insights.
Nevertheless, the findings provide important evidence that supports combination therapy even in patients with mild asthma. The approach of adding an inhaled glucocorticoid to rescue therapy represents a significant advance in addressing the risks faced by the estimated 50% to 70% of asthma patients with mild disease.
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Source: New England Journal of Medicine
