Triple therapy for COPD : Understanding evidence is complicated

Background: Recent Canadian and international guidelines for management of chronic obstructive pulmonary disease (COPD) recommend single inhaler triple therapy (long-acting muscarinic antagonist/longacting beta agonist/inhaled corticosteroid) as first-line treatment or as escalation from dual therapy for “high risk” patients who experienced at least 1 severe or 2 moderate exacerbations during the previous year. While they differ as to other eligibility criteria for triple therapy, these new recommendations could increase inappropriate prescriptions. In British Columbia, singleinhaler triple therapy is increasing rapidly. Aims: This Therapeutics Letter critically appraises available evidence about triple therapy for “high risk” COPD patients. Findings: No randomized controlled trial (RCT) has evaluated first-line triple therapy in people newly diagnosed with COPD. Three RCTs enrolled “high risk” patients (N=20,396) at a mean of 8 years after COPD diagnosis. Most were already using ICS and many had a history of asthma. Results cannot be extrapolated to treatment-naïve patients treated initially with triple therapy. We found unconvincing the RCT evidence that triple therapy reduces exacerbations. Like the US FDA’s Advisory Committee, we could not confirm that triple therapy reduces mortality. Furthermore, retrospective real-world data indicate that triple therapy achieves no significant reduction in exacerbations, but increases pneumonia and total mortality. Conclusions: Current evidence does not support first-line triple therapy in treatment-naïve COPD patients, nor routinely adding ICS for people already using a LAMA/LABA inhaler. Clinicians should prioritize smoking cessation, immunization, and inhaler technique over pharmacological intensification, and ensure evidence-informed shared decision-making.