Efficacy of as-needed budesonide/formoterol in mild asthma: pooled analysis of SYGMA 1 and 2

Introduction: The SYGMA 1 & 2 trials (NCT02149199; NCT02224157) showed as-needed budesonide/formoterol (BUD/FORM) was comparable to BUD maintenance in reducing exacerbation risk in mild asthma. Aim: To examine the efficacy of as-needed BUD/FORM and BUD maintenance for severe exacerbations using pooled data from SYGMA 1 & 2. Methods: Mild asthma patients were randomised to placebo twice daily (bid) + as-needed BUD/FORM 200/6 µg (n=3366) or BUD 200 µg bid + as-needed terbutaline (BUD maintenance; n=3369). Treatment adherence, number and rate of severe exacerbations, time to first severe exacerbation and inhaled ICS load data were compared for these two treatments. Results: Mean maintenance adherence was 69.7% and 69.0% for as-needed BUD/FORM and BUD maintenance arms, respectively. As-needed BUD/FORM was comparable to BUD maintenance in number of severe exacerbations (294 vs 310), proportion of patients with severe exacerbations (7.4% vs 7.8%), as well as annual rate (0.096 vs 0.104; RR 0.93 [0.77, 1.11]; p=0.408) and time to first severe exacerbation (HR 0.94 [0.79, 1.12]; p=0.463) (figure). Total median daily ICS delivered dose was 78% lower with as-needed BUD/FORM (51.8 µg) compared with BUD maintenance (240.2 µg). Conclusions: In mild asthma, as-needed BUD/FORM provided comparable efficacy in reducing the risk of severe exacerbation to BUD maintenance with only 22% of the total median daily ICS dose.