Triple therapy reduces exacerbations, improves control in moderate to severe asthma

Triple therapy, compared with dual therapy, was associated with fewer asthma exacerbations and modest improvements in asthma control in children and adults with moderate to severe asthma, according to a new meta-analysis.

“International guidelines recommend medium- or high-dose inhaled corticosteroids and long-acting beta agonists combinations (dual therapy), delivered from the same inhaler, as the preferred controller options for patients aged 6 years or older with persistent, moderate to severe asthma,” Lisa H. Y. Kim, MD, clinical scholar in the department of medicine at McMaster University in Hamilton, Ontario, Canada, and colleagues wrote in JAMA. “When patients’ symptoms remain uncontrolled despite this approach, the precise efficacy and adverse events of adding long-acting muscarinic antagonists is uncertain, contributing to existing weak (conditional) recommendations.”

Kim and colleagues performed a systematic review and meta-analysis to evaluate outcomes and adverse events associated with triple therapy compared with dual therapy.

Researchers reviewed MEDLINE, Embase, CENTRAL, International Clinical Trials Registry Platform (ICTRP), FDA and European Medicines Agency (EMA) databases from November 2017 to December 2020 and selected 20 randomized clinical trials that compared triple therapy vs, dual therapy. In total, the trials included 11,894 children and adults with moderate to severe asthma (mean age, 52 years; 57.7% female). Two reviewers extracted data and assessed risk for bias and used random-effects meta-analyses and the GRADE approach to assess the quality of the evidence.

The primary outcomes were severe asthma exacerbations, asthma control, quality of life, mortality and adverse events.

Triple therapy was significantly associated with reduced risk for severe asthma exacerbations compared with dual therapy, with high-certainty evidence (nine trials: 22.7% vs. 27.4%; RR = 0.83; 95% CI, 0.77-0.9). In addition, triple therapy was also associated with an improvement in asthma control compared with dual therapy (14 trials: mean difference in Asthma Control Questionnaire-7 scale, –0.04 (95% CI, –0.07 to –0.01), according to the results.

The researchers also found an association with increased dry mouth and dysphonia (10 trials: 3% vs. 1.8%; RR = 1.65; 95% CI, 1.14-2.38) among individuals on triple therapy compared with dual therapy. However, there were no significant differences in treatment-related and serious adverse events between triple therapy and dual therapy.

In addition, there were no significant differences in asthma-related quality of life scores or mortality between those assigned triple therapy or dual therapy.

These findings provide clear, high-quality evidence on benefits and harms of triple therapy to aid in asthma care and may prompt revision of current asthma guidelines, the researchers said in a related press release.

“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,” Kim said.

The study was published in JAMA in coordination with a presentation by the authors at the Advances in Asthma Therapies symposium during the American Thoracic Society International Conference.

References:

Kim LHY, et al. Am J Respir Crit Care Med. 2021;doi:10.1164/ajrccm-conference.2021.203.1.

Press Release.