International guidelines recommend dual therapy-that is, medium- or high-dose inhaled corticosteroids with long-acting inhaled [beta]2-agonists-in patients who have moderate to severe asthma. However, this treatment sometimes fails to control the condition. Another type of medication, long-acting muscarinic antagonists, can be added to dual therapy-referred to as triple therapy-but the benefits and risks are unclear. A systematic review and meta-analysis was undertaken to synthesize outcomes and adverse effects of triple versus dual therapy in adults and children with persistent, uncontrolled asthma.
Twenty randomized clinical trials that enrolled a total of 11,894 patients with moderate to severe asthma were included in the analysis. Compared with dual therapy, triple therapy was significantly associated with a lower risk of severe asthma exacerbations and improvement in asthma control.
However, triple therapy wasn't significantly associated with an improvement in asthma-related quality of life, and there was no significant difference between groups in all-cause mortality. Triple therapy was associated with increased dry mouth and dysphonia, but the overall incidence of serious adverse events wasn't significantly different between groups.
One limitation of the study was that it wasn't possible to determine which outcome component of severe exacerbation (hospitalization, ED visit, or treatment with a systemic corticosteroid) could be driving the differences in association.