Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma

This study evaluates the efficacy and safety of albuterol-budesonide compared with albuterol alone for rescue as needed in patients with moderate-to-severe asthma.

This is a multinational study. Patients included were ages 4 years and older on a medium to high dose of inhaled corticosteroid (ICS) or low to high ICS with long-acting β agonist at stable dosing for at least 3 months who had at least one severe asthma exacerbation in the prior 12 months. Patients excluded included those with chronic obstructive pulmonary disease or other pulmonary disease, use of systemic glucocorticoids within 3 months of screening, or use of biologic treatment within 3 months or for a duration of 5 half-lives before screening.

The study was conducted as a double-blind randomized parallel group trial over at least 24 weeks. Adults and adolescents were randomized into 3 groups: (1) higher dose – 160 ug budesonide with 180 ug albuterol; (2) lower dose – 80 ug budesonide with 180 ug albuterol; and (3) albuterol-alone – 180 ug albuterol via metered dose inhaler. Children ages 4 to 11 years received either the lower dose or the albuterol-alone treatment. Maximum daily dose was 12 inhalations (6 doses). The primary end point was the first severe asthma exacerbation in a time-to-event analysis. The secondary endpoints included rate of severe asthma exacerbations, total systemic glucocorticoid exposure, and response at 24 weeks to various asthma control questionnaires depending upon age.

A total of 3132 patients were randomized, of which the vast majority (97%) were 12 years and older. In the intention-to-treat analysis, the risk of severe exacerbation was 26% lower in the higher- dose group compared with the albuterol-alone group (hazard ratio 0.74; 95% confidence interval 0.62–0.89; P = .001) and 16% lower in the lower-dose group compared with albuterol-alone (hazard ratio 0.84; 95% confidence interval 0.71–1.0; P = .052), the latter of which was not significant. There were lower rates of systemic glucocorticoid use in the higher-dose and lower-dose groups compared with albuterol-alone. Adverse event rates were similar among the 3 groups, with most common events including nasopharyngitis, headaches, and upper respiratory infections.

In patients with moderate-to-severe asthma, use of a combined ICS + albuterol as needed for rescue significantly reduced the risk of severe asthma exacerbations. This approach also appeared to be safe with modest adverse effects that were distributed equally among all groups.

Asthma guidelines have evolved in the past 5 years. Studies have shown the efficacy and safety of use of ICS combined with formoterol such that the national guidelines deemed this the preferred approach in patients with moderate to severe asthma. Reduction in use of systemic corticosteroids is essential for morbidity and mortality related to asthma. This study demonstrated that ICS with albuterol is also a safe and effective option to be considered in these patients.