ICS-Formoterol Superior to Albuterol Only in 5–15-year-old Children

Source: Hatter L, Holliday M, Oldfield K, et al. Budesonide-formoterol versus salbutamol as reliever therapy in children with mild asthma (CARE): a 52-week, open-label, multicentre, superiority, randomised controlled trial. Lancet. 2025;406(10511):1473-1483; doi: 10.1016/S0140-6736(25)00861-X.Investigators from multiple institutions conducted a randomized clinical trial comparing the effectiveness of inhaled budesonide-formoterol reliever therapy vs short-acting beta-agonist (SABA) reliever treatment in children with mild asthma. Participants were children 5–15 years old who were enrolled at 15 sites in New Zealand. All study patients had a diagnosis of asthma and met 1 of the following criteria: SABA use for ≥3 consecutive days in previous 12 months, SABA use on an average of ≥2 days per month in previous 12 months, or an unscheduled visit for worsening asthma in previous 12 months. At enrollment, participants were randomized to budesonide 50 μg-formoterol 3 μg, 2 inhalations as needed, or SABA (salbutamol 100 μg) 2 inhalations as needed, for asthma symptoms. Study patients were followed for 52 weeks. The primary study outcome was annualized rate of asthma attacks per participant per year, with an asthma attack defined as an unscheduled visit for worsening asthma symptoms. A main secondary outcome was annualized rate of severe asthma attacks, defined as an unscheduled visit for asthma at which systemic corticosteroids were prescribed, or a hospital admission for asthma. Poisson regression was used to compare these outcomes among children in the 2 treatment groups. The proportion of participants in each treatment group with at least 1 asthma attack and the proportion with at least 1 severe attack were compared using logistic regression.Data on 360 children with mild asthma were analyzed, with 179 randomized to budesonide-formoterol and 181 to the SABA group. The mean age of these participants at enrollment was 10 ±2.9 years, and 77 (21%) had ≥1 severe asthma attack in the previous year. The annualized rate of asthma attacks per participant was 0.23 for those in the budesonide-formoterol group and 0.41 for children randomized to SABA (relative rate [RR], 0.55; 95% confidence interval [CI], 0.35, 0.86). The annualized rate of asthma attacks per participant was significantly less in those randomized to budesonide-formoterol than in those receiving SABA among patients 12–15 years old (RR, 0.06; 95% CI, 0.01, 0.43), but not in children 5–11 years old (RR, 0.72; 95% CI, 0.46, 1.12). The annualized rates of severe asthma attacks were 0.11 and 0.18 per participant, respectively, in children in the budesonide-formoterol or SABA treatment groups (RR, 0.60; 95% CI, 0.32, 1.14). Among patients randomized to budesonide-formoterol, 30 (17%) had at least 1 asthma attack, compared to 58 (32%) for those in the SABA group (odds ratio [OR], 0.43; 95% CI, 0.24, 0.75); the proportion having a severe attack were 9% and 15%, respectively (OR, 0.54; 95% CI, 0.26, 1.11).The authors conclude that use of budesonide-formoterol as reliever therapy was superior to SABA reliever treatment in preventing asthma attacks in children with 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 estimated to affect 10% to 15% of children worldwide and has a significant disease burden, including more than 10 million school days missed per year.1,2 The Symbicort Given as Needed in Mild Asthma (SYGMA) study noted reductions in asthma exacerbations with ICS-formoterol compared to SABA in children 12–17 years old.3 Global Initiative for Asthma recommends using an ICS and SABA, instead of SABA alone, for children 6–11 years old.4 However, no previous researchers compared ICS-formoterol to SABA alone in children younger than 12 years old.The results of the current investigation showed that in children aged 5–15 years old, using budesonide-formoterol instead of SABA-only treatment for mild asthma reduced the rate of asthma attacks by 45%. There was a similar side-effect profile, and no association with growth limitation was found. There was a difference between the 2 age groups, with a potential greater efficacy in children 12–15 years old at preventing asthma exacerbations compared to children 5–11 years old.Strengths of the current study include investigation in a high-risk population that had not been studied yet and 12-month duration. Limitations include small case numbers in subgroups, subjective parental report of symptoms, varied nature of individual clinical decision making separate from trial investigators, lack of blinding, and lack of dose counters to monitor inhaler use.In children 5–15 years old with mild asthma, budesonide-formoterol as-needed is superior to SABA-only as-needed.The results of this study suggest that combined ICS-SABA treatment probably should be the first-line therapy for children with mild asthma.