OBJECTIVES

Guidelines recommend that triple therapy with a long-acting β₂ agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS) is reserved for a select group of symptomatic patients with COPD who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and identify patients with the best risk-benefit profile for treatment.

METHODS

A systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD was conducted in five electronic databases. Outcomes included exacerbations and safety.

RESULTS

Of the 523 records, 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15–52% compared with LAMA/LABA, 15–35% compared to LABA/ICS and 20% compared to LAMA. For moderate or severe exacerbations, the patient-based number needed to treat ranged between approximately 25–50 (preventing one patient from having an event) and the event-based number needed to treat was around 3–11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a higher incidence of pneumonia with triple therapy (8%) and LABA/ICS (7%) than with LAMA/LABA (5%). There were important differences in study designs and populations indicating significant heterogeneity in cross-trial comparisons.

CONCLUSIONS

The decision to prescribe triple therapy should consider patient phenotypes, magnitude of benefit and increased risk of adverse events. To support treatment and funding decisions, future research from well-designed, robust, clinical trials is required to further define specific patient’s characteristics associated with the best risk-benefit profile for treatment.