When considering triple therapy for COPD, select patients carefully

New study says select patients with COPD phenotypes likely to respond to triple therapy

A greater reduction in the risk of moderate or severe exacerbations and improvement in lung function and quality of life were observed in patients receiving triple inhalation therapy for chronic obstructive pulmonary disease (COPD) compared with dual inhalation therapy or monotherapy, according to results of a meta-analysis of 21 trials in BMJ. However, no improvement in survival was seen with triple therapy (i.e., consisting of a combination of an inhaled corticosteroid (ICS), a long-acting beat-agonist (LABA), and long-acting muscarinic receptor antagonists [LAMA]) compared with other regimens, and triple therapy was associated with an increased risk of pneumonia when compared with a LMA/LABA dual inhalation regimen.  

“Considering that no survival benefit was associated with triple therapy, and increased risk of pneumonia was observed, our results might only apply to patients with symptomatic COPD, severe airflow limitation, and an exacerbation history, and any potential benefit could be lost if triple therapy is expanded to patients with mild COPD,” stated the study authors. “Careful identification of patients who might benefit most from triple therapy is required. Attempts should be made to identify patients with COPD phenotypes (e.g., eosinophil levels, patient characteristics, and exacerbation history) most likely to respond to the triple therapy,” they concluded. 

Zheng and colleagues conducted a meta-analysis of trials in patients with moderate to very severe COPD that compared triple inhalation therapy with a LABA, LAMA, and ICS with that of control interventions such as dual therapy with a LABA/LAMA, LABA/ICS, or LAMA/ICS or monotherapy with a LAMA, LABA, or ICS. A total of 21 trials were included. The trials used fixed triple therapy in a single inhaler, and 15 trials used separate triple therapy in different inhalers. The primary outcome assessed was moderate or severe exacerbations.  

The rate of moderate or severe exacerbations was significantly reduced with triple therapy compared with LAMA monotherapy (rate ratio 0.71 [95% CI 0.60–0.85]), LAMA/LABA dual therapy (0.78, 0.70–0.88), and ICS/LABA dual therapy (0.77, 0.66–0.91). Also, use of triple therapy was associated with significant improvements in trough forced expiratory volume in 1 second (FEV1) when compared with LAMA monotherapy and dual regimens of LAMA/LABA and LABA/ICS. Quality of life outcomes were also favorable for triple therapy. However, the analysis showed that triple therapy was not associated with any significant associations for all-cause mortality, and the risk of pneumonia events was significantly increased when compared with a LAMA/LABA regimen. Overall, the triple therapy was not associated with an increased risk of adverse events or cardiovascular events compared with the other regimens.   

Trelegy Ellipta fromGlaxoSmithKline is the first inhalation therapy that contains three medications in a single inhaler: fluticasone (ICS), umeclidinium (LAMA), and vilanterol (LABA). It is currently FDA approved for long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema, and to reduce exacerbations of COPD in patients with a history of exacerbations. When assessing the results of the meta-analysis, other available data, and current practice guidelines, triple therapy seems most appropriate for select patients who continue to have exacerbations despite the use of dual regimens that contain a LABA/LAMA or LABA/ICS. Also, addition of an ICS to a LABA/LAMA regimen may be well suited for patients with concurrent asthma or those with an elevated eosinophil count.  

For the full article, please visit for the January 2019 issue of Pharmacy Today.