Rescue combo therapy outshines albuterol alone for mild asthma

As-needed treatment with the combination of albuterol plus budesonide works better than albuterol alone for preventing severe exacerbations in patients with uncontrolled mild asthma, according to the phase IIIb BATURA trial.

The primary outcome of a severe exacerbation occurred less frequently with albuterol–budesonide vs albuterol both in the on-treatment efficacy population (5.1 percent vs 9.1 percent; hazard ratio [HR], 0.53, 95 percent confidence interval [CI], 0.39–0.73; p<0.001) and in the intention-to-treat population (5.3 percent vs 9.4 percent; HR, 0.54, 95 percent CI, 0.40–0.73; p<0.001). [N Engl J Med 2025;393:113-124]

Compared with albuterol alone, albuterol–budesonide was associated with lower annualized rate of severe asthma exacerbations (0.15 vs. 0.32; rate ratio, 0.47, 95 percent CI, 0.34–0.64) and reduced exposure to systemic glucocorticoids (mean total dose, 23.2 vs 61.9 mg per year).

As for safety, the overall incidence of adverse events (AEs) was similar between the albuterol–budesonide and albuterol groups (42.2 percent vs 43.5 percent, respectively). The most common AEs were upper respiratory tract infection, COVID-19, and nasopharyngitis. Inhaled glucocorticoid–associated local AEs occurred in less than 2 percent of patients in each group.

The incidence of serious AEs was low and similar between the two treatment groups (3.1 percent), and none were considered related to treatment. AEs led to treatment discontinuation in 1.2 percent of patients in the albuterol–budesonide group and in 2.7 percent of those in the albuterol group.

“The BATURA trial showed that as-needed albuterol–budesonide was efficacious in reducing the risk of severe asthma exacerbations among participants 12 years of age or older with uncontrolled disease despite treatment for mild asthma, although it should be noted that more than 97 percent of the participants were 18 years of age or older,” the investigators noted.

“The risk of a severe exacerbation was 47-percent lower with albuterol–budesonide than with albuterol [alone], which led to the trial being stopped after a planned interim analysis showed efficacy,” they added.

Fixed-dose, inhaled glucocorticoid–containing rescue therapy, including inhaled glucocorticoid–formoterol rescue therapy and as-needed inhaled glucocorticoid–albuterol, has been associated with a lower likelihood of exacerbations when compared with short-acting beta-agonist (SABA) rescue therapy in patients with mild asthma. [N Engl J Med 2019;380:2020-2030; N Engl J Med 2018;378:1865-1876; N Engl J Med 2007;356:2040-2052]

Taken together, the findings of the BATURA trial and the previous studies “support the use of inhaled glucocorticoid–containing rescue therapy for persons treated for mild asthma,” the investigators said.

BATURA included 2,516 mild asthma patients aged ≥12 years who had uncontrolled disease despite being on the National Asthma Education and Prevention Program Step 1 or Step 2 treatment, defined as either as-needed SABA only or as-needed SABA plus maintenance low-dose inhaled glucocorticoid or leukotriene-receptor antagonist.

The patients were randomly assigned to receive treatment with either a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two inhaler actuations of 90 μg and 80 μg, respectively) or 180 μg of albuterol (with each dose consisting of two inhaler actuations of 90 μg) on an as-needed basis for up to 52 weeks. 

The full analysis population comprised 2,421 patients (mean age 42.7 years, 68.3 percent female, 70.1 percent White), of which 1,209 were in the albuterol–budesonide group and 1,212 were in the albuterol group. A total of 1,797 patients (71.4 percent) completed the trial.