Combination therapy with a long-acting β2-agonist (LABA) plus an inhaled glucocorticoid for the management of asthma was not associated with a significantly higher risk for serious asthma-related events compared with treatment with an inhaled glucocorticoid alone. However, combination therapy was linked with significantly fewer asthma exacerbations, according to the results of a combined analysis of 4 clinical trials (ClinicalTrials.gov identifiers: NCT01444430, NCT01475721, NCT01471340, and NCT01845025) that compared treatment with an inhaled glucocorticoid plus a LABA (combination therapy) with use of an inhaled glucocorticoid alone. The results were published in The New England Journal of Medicine.1
Each of the 4 trials involved in the combined analysis targeted an enrollment of 11,664 adolescents (12-17 years of age) and adults with persistent asthma into a 26-week, multicenter, parallel, randomized, noninferiority trial. The primary outcome of the combined analysis was a composite of asthma-related intubation or death. Post-hoc secondary study outcomes included asthma exacerbations and serious asthma-related events.
Of the 36,010 participants in the intention-to-treat study, 3 asthma-related intubations were reported (2 in the inhaled-glucocorticoid group and 1 in the combination-therapy group) and there were 2 asthma-related deaths (both in the combination-therapy group) in 4 patients.
In the secondary analysis of serious asthma-related events (which was a composite of hospitalization, intubation, or death), 0.60% (108 of 18,006) of participants in the inhaled-glucocorticoid group and 0.66% (119 of 18,004) of participants in the combination-therapy group experienced ≥1 composite event (relative risk, 1.09; 95% CI, 0.83-1.43; P =.55). In addition, 11.7% (2100 of 18,006) of individuals in the inhaled-glucocorticoid group and 9.8% (1768 of 18,004) of those in the combination-therapy group experienced ≥1 asthma exacerbation (relative risk, 0.83; 95% CI, 0.78-0.89; P <.001).
The investigators concluded that these findings imply that the risk for asthma-related death or intubation is unlikely to be estimated precisely in prospective studies. The data from the combined analysis offer strong evidence to support the recent US Food and Drug Administration decision to remove the boxed safety warning related to combination therapy with a LABA plus an inhaled glucocorticoid for the treatment of asthma.2
1. Busse WW, Bateman ED, Caplan AL, et al. Combined analysis of asthma safety trials of long-acting β2-agonists. N Engl J Med. 2018;378(26):2497-2505.
2. Seymour SM, Lim R, Xia C, Andraca-Carrera E, Chowdhury BA. Inhaled corticosteroids and LABAs — removal of the FDA’s boxed warning. N Engl J Med. 2018;378(26):2461-2463.