Exacerbation risk after night-time waking due to asthma in SYGMA 1

Introduction: In mild asthma, as-needed budesonide/formoterol (BUD/FORM) reduces exacerbation risk vs as-needed terbutaline, with similar reduction to BUD maintenance + as-needed terbutaline (SYGMA 1; NCT02149199). Aims and Objectives: A post-hoc analysis of SYGMA 1 examined the short-term risk of exacerbations following night-time waking due to asthma. Methods: 3836 mild asthma patients received placebo twice-daily (bid) + terbutaline 0.5mg as-needed, placebo bid + as-needed BUD/FORM 200/6µg or BUD 200µg bid + as-needed terbutaline. Cox regression analysis estimated time to first severe or moderate/severe exacerbation in the 21 days after two consecutive nights' waking due to asthma. Results: The frequency of night-time waking due to asthma was low (median nights: as-needed terbutaline, 5.7%; as-needed BUD/FORM, 2.9%; BUD maintenance, 1.8%). More patients had ≥1 episode of two consecutive nights' waking in the 12-month study with as-needed terbutaline (64.5%) than with as-needed BUD/FORM (52.8%, p<0.0001) or BUD maintenance (45.2%, p<0.0001). As-needed BUD/FORM and BUD maintenance significantly reduced severe exacerbations in the following 21-days vs as-needed terbutaline, with similar results for moderate/severe exacerbations (Figure). Conclusions: In mild asthma, as-needed BUD/FORM reduces short-term exacerbation risk after two consecutive nights of asthma waking vs as-needed terbutaline, with comparable efficacy to BUD maintenance.