Adding a long-acting muscarinic antagonist (LAMA) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) reduces exacerbations in people with moderate to severe persistent asthma, a systematic review and meta-analysis shows.

However the use of triple therapy over dual therapy (ICS and LABA) resulted in only small improvements in lung function, and little to no change in symptoms and quality of life, according to the study conducted by  researchers from McMaster University, Canada.

Published in JAMA, their review included data from 20 randomised clinical trials and 11, 894 adults and children with asthma treated with triple therapy (ICS, LABA, and LAMA), compared with dual therapy (ICS plus LABA).

Evidence from nine RCT provided “high-certainty evidence” that triple was significantly associated with a reduction in severe exacerbation risk compared to dual therapy (22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]).

There was also modest but “potentially clinically unimportant” improvements in asthma control as measured a mean difference of -0.04 in ACQ-7 scale, equivalent to 65% vs 63% of patients achieving minimal important differences.

In terms of lung function spirometry parameters, triple therapy was significantly associated with a higher percentage of patients achieving a 200-mL increase from baseline compared with dual therapy (47% vs 37%; RR, 1.27 [95% CI, 1.22 to 1.32]).

However there were no significant differences in asthma-related quality of life and mortality between dual and triple therapy.

Triple therapy was significantly associated with increased dry mouth and dysphonia but treatment-related and serious adverse events were not significantly different between groups.

Presenting the results at the ATS 2021 meeting, the study authors said they should be seen in context of asthma exacerbation risk, with a history of a severe exacerbations in the previous year being a key factor.

“Thus, clinicians should also consider the baseline risk of exacerbation among patients being considered for triple vs dual therapy,” they said.

Although no difference was seen in patients at high vs low risk for severe exacerbations was detected in the review, they said its findings “strengthen the recommendation to add a LAMA to medium- to high-dose ICS plus LABA therapy for individuals at high risk of exacerbations and to rewrite the underlying rationale to do so.”

“These findings raise the notion that patient selection and consideration of risk for future exacerbation are imperative to identify those who may benefit the most from addition of a LAMA to ICS plus LABA as triple therapy,” they said.

“Our findings provide clear, high-quality evidence on the benefits and harms of triple therapy that will inform asthma care and should prompt revision of current asthma guidelines,” they concluded.

“If we can reach optimal control of patients’ asthma and reduce asthma exacerbation rates through the LAMA add-on therapy, patients may be able to avoid other treatments that carry a higher risk of adverse events, such as oral corticosteroids, or therapies that are substantially more expensive, such as biologics,” said Dr Lisa Kim, lead author of the study.

Disclosures: The study authors reported receipt of grants or payments from AstraZeneca, GSK, Medimmune, Genentech, Bayer, Merck, Novartis, Covis, Teva, Sage and Chiesi.