Clarke, G W

Abstract Introduction Inhaled corticosteroid/fast-acting beta2-agonist combinations are recommended over albuterol-alone as rescue in asthma due to superior exacerbation reduction. In adults with asthma, BATURA and MANDALA demonstrated as-needed albuterol-budesonide 180/160 μg reduced the risk of severe exacerbation by 46% in mild and 28% in moderate-to-severe asthma for patients aged ≥18 years versus albuterol 180 μg. However, albuterol is the long-held rescue therapy standard for treatment of bronchoconstriction. In the ALbuterol-budesonide Treatment in Acute Airway Obstruction (ALTA) (NCT05555290) study, repetitive albuterol-budesonide 180/160 ug versus albuterol 180 ug treatment resulted in equally rapid improvement in lung function over 60 minutes and provided enhanced bronchodilation at 480 minutes post-mannitol challenge: least squares mean/LSM(standard error/SE) [95%CI] difference in ΔFEV1=91.2 (27.4) [36.7-145.7] mL. This post-hoc analysis of ALTA evaluated whether baseline lung function affects treatment response. Methods ALTA was a Phase 3b, multicenter, randomized, double-blind, 2-period, crossover study evaluating efficacy of repetitive albuterol-budesonide 180/160 μg vs albuterol 180 μg in adults with mild asthma experiencing ≥15% fall in FEV1 with cumulative mannitol exposure ≤635 mg. Inclusion criteria included use of short-acting beta2-agonist as the only pre-enrollment therapy for ≥4 weeks and pre-challenge FEV1 ≥1.500 L and 60%-<90% of predicted. Participants received albuterol-budesonide or albuterol at end-mannitol challenge (time 0) and 20, 40, and 60 minutes thereafter. FEV1 was assessed starting pre-mannitol challenge (-30 minutes) and over 480 minutes post-challenge. For participants with baseline FEV1 60%-<80% and 80%-<90% predicted, LSM(SE) [95%CI] difference between treatment arms in ΔFEV1 from time 0 min at 480 minutes was analyzed using a linear mixed effects model. Results 88 randomized participants receiving ≥1 dose of study drug were included: mean(SD) age=44.5(13.7) years; 56.8% female; mean(SD) FEV1=2.462(0.540) L (76.7[7.7]% predicted). 56 participants had baseline FEV1 ≥60%-<80% predicted; 32 had baseline FEV1 80%-<90% predicted. Percent fall in FEV1 post-challenge was similar between lung function subgroups. Improvement in FEV1 post-mannitol (time 0 min) at 480 min was greater with albuterol-budesonide vs albuterol treatment for both FEV1 subgroups: LSM(SE) [95%CI] difference 71.0(29.8) [11.0-131.0] mL, p = 0.021 in the lower and 114.0(55.1) [1.0-227.0] mL, p = 0.048 in the higher baseline FEV1 participants (Figure). There was no significant difference in the treatment by subgroup interaction, suggesting consistent treatment efficacy between subgroups. Conclusions Albuterol-budesonide relieves acute obstruction better than albuterol over time in mild asthma whether or not baseline lung function falls within a normal range. This abstract is funded by: AstraZeneca