Safety of budesonide/formoterol maintenance and reliever therapy in asthma trials

SummaryBackgroundThe safety of long-acting β2-agonists (LABAs) in asthma is debated. This study examined the safety of the inhaled corticosteroid (ICS)/LABA combination budesonide/formoterol dry powder inhaler used as maintenance and reliever therapy versus combination treatments based on guideline recommendations.MethodsSafety data from six double-blind, randomised clinical trials (RCTs) in asthma where budesonide/formoterol was used as maintenance and reliever therapy for at least 6 months were reviewed (N=14 346). All-cause mortality and asthma-related serious adverse events (SAEs) (co-primary endpoints), overall and cardiac SAEs, and discontinuations due to adverse events (DAEs) were assessed. Estimated Mantel–Haenszel (MH) relative risks (RR) with this regimen versus comparators were calculated.ResultsThere was no increase in all-cause mortality with budesonide/formoterol maintenance and reliever therapy (four deaths [0.07%] versus nine [0.10%]; pooled MH RR 0.70, 95% confidence interval [CI] 0.21–2.30). Asthma-related SAEs were reduced with budesonide/formoterol maintenance and reliever therapy: 41 (0.73%) versus 121 (1.38%); pooled MH RR 0.59, 95% CI 0.42–0.85. All-cause and asthma-related DAEs were also reduced with budesonide/formoterol maintenance and reliever therapy: pooled MH RR 0.60 (95% CI 0.46–0.79) and 0.43 (0.28–0.68), respectively. Overall and cardiac-related SAEs were comparable between treatment groups: pooled MH RR 0.96 (95% CI 0.82–1.14) and 1.26 (0.72–2.22), respectively.ConclusionBudesonide/formoterol dry powder inhaler maintenance and reliever therapy was well tolerated in RCTs versus fixed-dose alternatives and not associated with increased risk of death or cardiac-related SAEs and DAEs, and asthma-related SAEs and DAEs were significantly reduced. Given the limitations of RCTs, particularly exclusion of patients with co-morbidities, ongoing surveillance is appropriate