Introduction:

In the MANDALA trial, as-needed albuterol–budesonide 180/160 µg lowered the risk of severe asthma exacerbations by 27% compared to as-needed albuterol 180 µg (based on time to first exacerbation) and reduced annualized severe exacerbation rates by 24% in patients aged 12 years and older. This post-hoc analysis focused on evaluating how early this benefit appears—specifically, in the first three months after initiating treatment and compared the magnitude of shorter- vs longer- term exacerbation risk reduction in patients aged > 12 years.

Methods:

1. Population: MANDALA study enrolled symptomatic asthma patients aged ≥4 years with ≥1 severe exacerbation in the prior year, already on GINA 3–5 ICS-containing maintenance therapy.
2. Study Arms:
   1. Albuterol–budesonide 180/160 µg (n=1013)
   2. Albuterol 180 µg (n=1014)
3. Analysis Periods: First 3 months’ post-randomization and total study duration.
4. Study Assessments:
   1. Time-to-first exacerbation in the first 3 months post-randomization in patients ≥12 years
   2. Annualized exacerbation rate based on 3-month exacerbation occurrence in patients ≥12 years 

Results:

• Demographics: Mean age ~50.6 years; 63.7% female in albuterol–budesonide group and 67.2% in albuterol group.
• Follow-up Duration: Mean exposure of 44 weeks; maximum 108 weeks.
• Number of patients with a severe exacerbation:
  • For the MANDALA study duration:
    • Albuterol-budesonide 180/160 µg (N=1013): 207 (20.4%)
    • Albuterol 180 µg (N=1014): 266 (26.2%)
  • In the first 3 months’ post-randomization:
    • Albuterol-budesonide 180/160 µg (N=1013): 106 (10.5%)
    • Albuterol 180 µg (N=1014): 144 (14.2%)

Conclusion:

Albuterol–budesonide used as rescue therapy provides a rapid and sustained reduction in severe exacerbation risk and annualized exacerbation rates in patients aged ≥12 years. Benefits are evident as early as three months’ post-initiation and similar to those seen long-term, supporting its early use in clinical practice for moderate-to-severe asthma.

Am J Respir Crit Care Med 2025; 211: A1287

American Thoracic Society 2025 International Conference, May 18-21, San Francisco