Albuterol-Budesonide Superior to Albuterol Alone for Mild Asthma

Source: LaForce C, Albers F, Danilewicz A, et al. As-needed albuterol-budesonide in mild asthma. New Engl J Med. 2025;393(2):113-124; doi: 10.1056/NEJMoa2504544.Investigators from multiple institutions conducted a doubleblind randomized clinical trial to compare the effectiveness of albuterol-budesonide to albuterol alone in preventing severe exacerbations in children and adults with uncontrolled mild asthma. All study participants were enrolled remotely using a telehealth platform. Children ≥12 years old and adults with physician-documented asthma were eligible for participation if their asthma was treated with a short-acting beta agonist (SABA) alone or in combination with maintenance treatment with low-dose inhaled glucocorticoids or a leukotriene-receptor antagonist. In addition, to be enrolled, participants had to have uncontrolled asthma, defined as use of SABA on ≥2 days during the prior 2 weeks, and have a score on the Asthma Impairment and Risk Questionnaire indicative of uncontrolled symptom. Study participants were randomized to receive albuterol-budesonide in a fixed dose (180 μg of albuterol and 160 μg of budesonide) or albuterol (180 μg) alone on as-needed basis to treat asthma symptoms for 12 to 52 weeks. The primary outcome was first severe asthma exacerbation, defined as receipt of systemic corticosteroids, emergency department or urgent care visit, or hospitalization, because of asthma. The primary outcome was assessed in the on-treatment population, including data while a participant was on the study drug and had not had an increase in maintenance therapy. Secondary outcomes included first severe exacerbation in the intention-to-treat population and annualized rate of severe exacerbations. Outcomes were compared for participants in the 2 treatment groups.A total of 2,516 participants were randomized; 1,797 completed the study, including 903 in the albuterol-budesonide group and 894 in the albuterol group. The mean age of study participants was 42.7 ± 14.5 years; 68 (2.8%) were <18 years old. Among all participants, 74.4% were on a SABA alone at the time of randomization. The mean number of inhalations per day during the study was 1.5 ± 1.7 for those in the albuterol-budesonide group and 1.8 ± 2.0 for those randomized to albuterol alone. In the on-treatment population, the rate of severe asthma exacerbation was 5.1% for those in the albuterol-budesonide group and 9.1% for the albuterol group (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39, 0.73). Because of this difference in efficacy, the trial was stopped early. In the intention-to-treat population, the rate of severe exacerbations was 5.3% and 9.4%, respectively, for participants randomized to albuterol-budesonide or albuterol (HR, 0.54; 95% CI, 0.40, 0.73). The annualized rate of severe asthma exacerbations was also significantly lower in those in the albuterol-budesonide group than in participants randomized to albuterol (0.15 vs 0.32; rate ratio, 0.47; 95% CI, 0.34, 0.64).The authors conclude that as-needed use of albuterol-budesonide was superior to albuterol alone in preventing severe exacerbations in patients ≥12 years old with uncontrolled mild asthma.Dr Chan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Asthma is the most common chronic condition of childhood, with mild asthma affecting 50% to 75% of children with asthma.1,2 Mild asthma is generally characterized as having infrequent symptoms and exacerbations. However, those with mild asthma may still have severe exacerbations, so control of symptoms is critical.3 While albuterol-only inhalers were previously favored for mild asthma rescue treatment, the Global Initiative for Asthma now recommends an inhaled corticosteroid (ICS) with fast-acting bronchodilator for patients 12 years old and older, and research results suggest that ICS with a bronchodilator (formoterol or albuterol) is superior to albuterol alone.4The authors of the current study performed a multicenter, virtual study to investigate the efficacy of budesonide with albuterol compared to albuterol alone in individuals 12 years or older for uncontrolled mild asthma. They found that albuterol-budesonide as-needed reduced the risk of severe asthma exacerbations in patients 12 years and older and decreased total annual systemic corticosteroid exposure.Strengths of the current study include its multicenter, doubleblind approach and large sample size. Limitations include the many patients lost to follow-up (possibly related to the virtual study approach) and lack of lung function testing or exhaled nitric oxide; despite a total population of 1,797 completing the study, only 68 participants were between 12 and <18 years of age.In patients 12 years of age and older, albuterol-budesonide appears to be superior to albuterol alone. Further studies in the pediatric patient age group are needed.