B22-18 Impact of As-needed Albuterol-budesonide on Symptoms in Moderate-to-severe Asthma: A Mandala Post-Hoc Analysis

Rationale In MANDALA, as-needed albuterol-budesonide 180/160 µg reduced asthma exacerbation risk by 28% versus albuterol 180 µg in symptomatic moderate-to-severe patients aged ≥18 years. Given that albuterol is the long-held standard for treating asthma symptoms, this post-hoc analysis assessed efficacy of as-needed albuterol versus albuterol-budesonide with respect to nighttime and daytime symptom burden for patients with and without exacerbations. Methods Patients in MANDALA completed symptom diaries twice daily: Nighttime 0 (no asthma symptoms), 1 (aware of, but can tolerate, asthma symptoms), 2 (asthma causing enough discomfort to interfere with sleep), 3 (unable to sleep due to asthma); Daytime 0 (no asthma symptoms), 1 (aware of, but can tolerate, asthma symptoms), 2 (asthma causing enough discomfort to interfere with normal activities), 3 (unable to do normal activities due to asthma). We assessed the likelihood of a symptom-free (score: 0) or problematic-symptom night or day (scores: 2 and 3; sleep or normal activities disrupted) among all patients ≥18 years and those who did or did not experience exacerbation with as-needed albuterol-budesonide versus albuterol: ORs [95% CI] via an adjusted logistic mixed model including baseline nighttime or daytime symptoms. Results 975 patients used albuterol-budesonide (305,778 on-study patient-nights, 16.9% with missing scores; 305,666 on-study patient-days, 17.5% missing scores) and 978 used albuterol (296,843 on-study patient-nights, 16.4% missing scores; 296,891 on-study patient-days, 16.8% missing scores). Model-estimated probability of a symptom-free night was higher in the albuterol-budesonide group (0.35 vs 0.28, OR [95% CI]=1.38 [1.05-1.83]; p = 0.023) (Figure). For non-exacerbating patients, the probability of a symptom-free night was higher with albuterol-budesonide (0.41 vs 0.32, OR [95% CI]=1.41 [1.03-1.94]; p = 0.035). For the total population and those without exacerbations, as-needed albuterol-budesonide also resulted in a lower likelihood of a problematic-symptom night (0.014 vs 0.020, OR [95% CI]=0.71 [0.57-0.88]; p = 0.001; 0.011 vs 0.015, OR [95% CI]=0.73 [0.57-0.93]; p = 0.012, respectively). The likelihood of a symptom-free or a problematic-symptom night for patients treated with as-needed albuterol-budesonide vs albuterol for those with or without exacerbations did not differ statistically (Treatment x Exacerbation Occurrence interaction p = 0.22 and 0.64, respectively). Daytime symptom endpoints did not differ between treatment arms for the total population or those with or without exacerbations. Conclusions As-needed albuterol-budesonide versus albuterol reduces exacerbation risk and nocturnal symptom burden-even for non-exacerbating patients. Nocturnal symptoms are associated with increased nighttime airway inflammation and can precede exacerbations, suggesting that the effect of albuterol-budesonide on nocturnal inflammation may contribute to the decrease of symptoms and exacerbations. This abstract is funded by: The study was funded by Bond Avillion 2 Development LP. Statistical analyses presented here and medical writing support were funded by AstraZeneca