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    Respiratory

    (407) As-needed albuterol–budesonide decreases risk of severe asthma exacerbation in the first three months post-randomization compared to albuterol in patients treated for moderate-to-severe asthma: MANDALA post-hoc analysis

    Wednesday, October 29, 2025

      Presenter(s)

    • Emily Robb, PharmD

      Post-Doctoral Fellow, Medical Information and Medical Affairs Strategy
      BioPharmaceuticals, US Medical, AstraZeneca
      Wilmington, Delaware, United States

      • Primary Author(s)

    • Bradley E. Chipps, MD

      Allergist and Immunologist
      Capital Allergy and Respiratory Disease Center, Sacramento, CA, United States
      Sacramento, California, United States

      • Co-Author(s)

    • Alberto Papi, MD

      Professor of Respiratory Medicine
      Department of Respiratory Medicine, University of Ferrara Medical School, Ferrara, Italy
      Ferrara, Emilia-Romagna, Italy

    • Richard Beasley, DSc

      Director, Founder, Asthma Programme Lead, Oxygen Programme Co-Lead
      Medical Research Institute of New Zealand, Wellington, New Zealand
      Wellington, Wellington, New Zealand

    • Reynold A. Panettieri Jr., MD

      Vice Chancellor for Translational Medicine and Science
      Rutgers Institute for Translational Medicine and Science, Rutgers, The State University of New Jersey, NJ, United States
      New Brunswick, New Jersey, United States

    • Elliot Israel, MD

      Gloria M. and Anthony C. Simboli Endowed Chair in Asthma Research
      Divisions of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
      Boston, Massachusetts, United States

    • Susan Kuchera, n/a

      Program director
      Abington Family Medicine
      Jenkintown, Pennsylvania, United States

    • Ileen Gilbert, MD

      Medical Director, Respiratory
      AstraZeneca
      Wilmington, Delaware, United States

    • Lynn Dunsire, MSc

      Statistical Science Director
      BioPharmaceuticals Research and Development, AstraZeneca, Cambridge, United Kingdom
      Cambridge, England, United Kingdom

    • Olami Sobande, MD

      Global Clinical Program Lead
      BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MA, United States
      Gaithersburg, Maryland, United States

    • Omar Motawakel, MD, MSHS

      Senior Medical Affairs Director - R&I , US
      BioPharmaceuticals, US Medical, AstraZeneca
      Wilmington, Delaware, United States

    • Tim Harrison, MD

      Head of Inhaled Asthma Portfolio
      BioPhamaceuticals, Global Medical Affairs, AstraZeneca Cambridge, United Kingdom
      Cambridge, England, United Kingdom

    • Robert Fogel, MD

      Vice President, Global Medical Affairs, Respiratory & Immunology, AstraZeneca
      BioPharmaceuticals R&D, AstraZeneca
      Gaithersburg, Maryland, United States

    • Neil Skolnik, MD

      Professor of family and community medicine
      Sidney Kimmel Medical College
      Philadelphia, Pennsylvania, United States


    Background:     : In MANDALA (NCT03769090), as-needed albuterol–budesonide (ALB–BUD) 180/160 µg reduced severe asthma exacerbation risk by 27% versus as-needed albuterol (ALB) 180 µg (time-to-first exacerbation) and decreased annualized severe asthma exacerbation rates by 24% in patients ≥12 years receiving inhaled corticosteroid–containing GINA 3−5 maintenance therapy. Minimum enrollment was 24 weeks.

    Objective: : To explore the benefit of as-needed ALB–BUD versus ALB early after the initiation of the tested rescue treatments and compare the magnitude of shorter- versus longer-term exacerbation risk reduction.

    Methods: : This post-hoc analysis of MANDALA assessed time-to-first severe exacerbation in the first 3 months post-randomization and annualized exacerbation rate in patients ≥12 years on maintenance therapy and as-needed ALB–BUD 180/160 µg versus ALB 180 µg. Time-to-first severe exacerbation was analyzed using a Cox proportional hazards model, and annualized exacerbation rate by a negative binomial regression model (both adjusted for age, region, and prior-year exacerbations).

    Results: : Of 2027 patients, 1013 received ALB–BUD 180/160 µg (mean [SD] age=50.6 [15.1]; 63.7% female; 22.2% with ≥2 prior-year severe exacerbations) and 1014 received ALB 180 µg (age=50.7 [15.5]; 67.2% female; 20.3% with ≥2 prior-year severe exacerbations). Average exposure to randomized treatment was 44 weeks and maximum duration on study was 108 weeks. For patients using ALB–BUD versus ALB, risk of a first severe exacerbation was reduced by 28% in the first 3 months (hazard ratio [95% CI]: 0.72 [0.56, 0.92]; P=0.009) and by 27% during the study duration (0.73 [0.61, 0.88]; P< 0.001). Annualized rates of severe exacerbations based on exacerbation occurrence in the first 3 months were 0.61 (0.43, 0.85) with ALB–BUD and 0.81 (0.58, 1.11) with ALB, which is a 25% reduction in the annualized rate of exacerbations in the first 3 months (rate ratio [95% CI]: 0.75 [0.58, 0.98]; P=0.033) versus a 24% reduction for the study duration (0.76 [0.62, 0.93]; P=0.008).

    Conclusions: : In patients ≥12 years with moderate-to-severe asthma on as-needed ALB–BUD 180/160 µg versus ALB 180 µg, severe exacerbation risk and annualized exacerbation rates were significantly decreased already in the first 3 months, similar to those seen long-term, indicating a rapid protective effect of the ALB–BUD combination. Clinicians and patients switching from albuterol to albuterol–budesonide rescue can anticipate reduction in severe exacerbation risk within 3 months of ALB–BUD initiation, which is sustained long-term.

    Sponsorship:: Bond Avillion 2 Development LP and AstraZeneca.