Combined Analysis of Asthma Safety Trials of Long-Acting β2-Agonists

Busse WW, Bateman ED, Caplan AL, Kelly HW, O'Byrne PM, Rabe KF, Chinchilli VM. N Engl J Med. 2018 Jun 28;378(26):2497-2505. [CrossRef] [PubMed]

Safety concerns regarding long-acting β2-agonists (LABAs) in asthma management were initially identified in the 2006 SMART trial in which the risk of death was increased. In 2010, the Food and Drug Administration (FDA) mandated that the four companies marketing LABAs for asthma perform prospective, randomized, controlled trials comparing the safety of combination therapy with a LABA plus an inhaled glucocorticoid with that of an inhaled glucocorticoid alone. In conjunction with the FDA, the manufacturers harmonized their trial methods to allow an independent joint oversight committee to provide a final combined analysis of the four trials. The joint oversight committee performed a combined analysis of the four trials comparing an inhaled glucocorticoid plus a LABA (combination therapy) with an inhaled glucocorticoid alone. The primary outcome was a composite of asthma-related intubation or death. Post hoc secondary outcomes included serious asthma-related events and asthma exacerbations. Among the 36,010 patients in the intention-to-treat study, combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations.