Research Summary

As-Needed Albuterol–Budesonide in Mild Asthma

Miranda Manier, BA

Key Highlights

  • As-needed albuterol–budesonide significantly reduced the risk of severe asthma exacerbations compared with albuterol alone in patients with mild asthma.
  • The hazard ratio for severe exacerbations was approximately 0.53–0.54, favoring the combination therapy (P < .001).
  • The annualized rate of severe exacerbations and systemic glucocorticoid use were notably lower in the albuterol–budesonide group.
  • Safety profiles were similar between treatment groups.

In a phase 3b randomized trial, as-needed use of a combination of albuterol and budesonide significantly reduced the risk of severe asthma exacerbation compared with albuterol alone in patients with uncontrolled mild asthma. The study demonstrated that the hazard of experiencing a first severe exacerbation was roughly halved in the combination therapy group. Additionally, the annualized rate of exacerbations and systemic glucocorticoid exposure were substantially reduced.

While prior evidence supported the use of as-needed albuterol–budesonide in moderate-to-severe asthma, data for patients with mild asthma were lacking. This study addressed the need for effective exacerbation prevention strategies in individuals whose disease remained inadequately controlled despite standard SABA use or low-dose inhaled therapy.

Researchers conducted a fully virtual, decentralized, multicenter, double-blind, event-driven trial in participants aged 12 years or older with uncontrolled mild asthma. Eligible participants were already being treated with a short-acting β2-agonist (SABA), either alone or with a low-dose inhaled corticosteroid or leukotriene-receptor antagonist. Subjects were randomized in a 1:1 ratio to receive either albuterol–budesonide (180 μg albuterol + 160 μg budesonide per dose) or albuterol alone (180 μg per dose), administered on an as-needed basis over a period of up to 52 weeks. The primary endpoint was time to first severe exacerbation in the on-treatment efficacy population, with a key secondary analysis in the intention-to-treat population. Additional outcomes included annualized exacerbation rates and systemic steroid exposure.

Among the 2516 participants randomized, 2421 were included in the full analysis population, with 97.2% aged 18 years or older. At baseline, 74.4% used SABA alone. The trial was stopped early at a prespecified interim analysis due to clear evidence of efficacy. In the on-treatment population, 5.1% of participants receiving albuterol–budesonide experienced a severe exacerbation versus 9.1% in the albuterol-only group (hazard ratio, 0.53; 95% CI, 0.39–0.73). In the intention-to-treat analysis, results were similarly favorable (5.3% vs 9.4%; hazard ratio, 0.54; 95% CI, 0.40–0.73). Annualized rates of severe exacerbations were also lower in the combination group (0.15 vs 0.32; rate ratio, 0.47; 95% CI, 0.34–0.64), as was mean annual systemic glucocorticoid dose (23.2 mg vs 61.9 mg). Adverse events occurred at comparable rates between groups.

“As-needed use of albuterol–budesonide resulted in a lower risk of a severe asthma exacerbation than as-needed use of albuterol alone among participants with disease that was uncontrolled despite treatment for mild asthma,” the study authors concluded.

Reference:
LaForce C, Albers F, Danilewicz A, et al. As-needed albuterol-budesonide in mild asthma. N Engl J Med. Published online May 19, 2025. doi:10.1056/NEJMoa2504544