A LARGE randomized trial has found that as-needed use of a fixed-dose combination of albuterol and budesonide significantly reduces the risk of severe asthma exacerbations compared to albuterol alone in patients with mild asthma.
This phase 3b, double-blind, multicenter trial enrolled over 2,500 participants aged 12 and older whose mild asthma remained uncontrolled despite treatment with a short-acting β2-agonist (SABA), with or without a low-dose inhaled corticosteroid or leukotriene-receptor antagonist. Participants were randomized to receive either albuterol–budesonide (180 μg and 160 μg per dose, respectively) or albuterol alone (180 μg per dose) on an as-needed basis for up to 52 weeks. The primary endpoint was the time to first severe asthma exacerbation in the on-treatment efficacy population, with key secondary endpoints including exacerbation rates and systemic steroid exposure.
The trial was stopped early at a prespecified interim analysis due to efficacy. Among the 2,421 participants in the full analysis population, 5.1% of those using albuterol–budesonide experienced a severe exacerbation compared to 9.1% in the albuterol-only group (hazard ratio, 0.53; 95% CI, 0.39 to 0.73). Similar results were observed in the intention-to-treat population (5.3% vs. 9.4%; HR, 0.54; 95% CI, 0.40 to 0.73; P<0.001 for both comparisons). The annualized rate of severe exacerbations was more than halved with the combination therapy (0.15 vs. 0.32; rate ratio, 0.47), and participants on the combination also required lower annual doses of systemic glucocorticoids (23.2 mg vs. 61.9 mg). Importantly, adverse event profiles were similar between the two groups, suggesting the combination inhaler was not associated with increased safety concerns. These findings support a shift in mild asthma management toward as-needed anti-inflammatory reliever therapy rather than relying on bronchodilators alone, even in cases traditionally managed without daily controller medications. Reference: LaForce C et al. As-Needed Albuterol–Budesonide in Mild Asthma. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2504544. [Online ahead of print].
