Adding a LAMA to ICS/LABA Therapy: A Meta-analysis of Triple Combination Therapy in COPD

Inhaled corticosteroid (ICS)/long-acting β₂-agonist (LABA) combination is commonly prescribed to treat COPD; therefore, we performed a meta-analysis on the effect of adding a long-acting muscarinic receptor antagonist (LAMA) to ICS/LABA combination in COPD.

Studies were identified by searching in different databases the randomized controlled trials that investigated the effect of ICS/LABA/LAMA combination in COPD. The primary end points were the effect of triple therapy on trough FEV₁, risk of acute exacerbation of COPD (AECOPD), and risk of cardiovascular serious adverse events (SAEs), compared with ICS/LABA combination. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the quality of evidence.

Thirteen randomized controlled trials including 15,519 patients with COPD (ICS/LABA/LAMA combination, 53.1%; ICS/LABA combination, 46.9%) were meta-analyzed. ICS/LABA/LAMA combination improved trough FEV₁ (mean difference, +104.86 mL; 95% CI, 86.74-122.99; high quality of evidence) and protected against AECOPD (relative risk, 0.78; 95% CI, 0.71-0.85; high quality of evidence) vs ICS/LABA combination. For every approximately four patients treated with triple therapy, one increased FEV₁ > 100 mL, and approximately 26 patients had to be treated for 1 year with ICS/LABA/LAMA combination to prevent one AECOPD, compared with ICS/LABA combination. Adding a LAMA to ICS/LABA therapy did not modulate the risk of cardiovascular SAEs (moderate quality of evidence).

Triple therapy provides significant clinical benefit in patients with COPD on ICS/LABA combination. ICS/LABA therapy can be escalated to triple therapy without a real risk to increase cardiovascular SAEs when a LAMA is added to the combination.

ClinicalTrials.gov; No.: CRD42018095300; URL: www.clinicaltrials.gov.