Combination of a Long-Acting β-Agonist and Muscarinic Antagonist Is More Effective Than Either Agent Alone in Advanced COPD

Clinicians have several options for treating patients with stable chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease recommends long-acting bronchodilators for higher-risk patients and those whose symptoms are not controlled with short-acting agents (NEJM JW Gen Med Sep 13 2012). FDA-approved long-acting β-agonists (LABAs) include twice-daily salmeterol (Serevent), formoterol (Foradil), and arformoterol (Brovana), and once-daily indacaterol (Arcapta Neohaler); long-acting muscarinic antagonists (LAMAs) that are approved for treating patients with COPD include twice-daily aclidinium (Tudorza Pressair) and once-daily tiotropium (Spiriva) and umeclidinium (Incruse Ellipta). Addition of inhaled corticosteroids (ICS) is recommended for patients with severe airflow obstruction or continued exacerbations. The combination of a LABA and a LAMA appears to be more efficacious than either agent alone, and some studies suggest that triple therapy with a LABA, a LAMA, and ICS confers even greater benefits.

Combination umeclidinium and vilanterol (a LABA) is FDA-approved for COPD in a once-daily dry powder inhaler (Anoro Ellipta). Researchers examined the long-term efficacy and safety of combination umeclidinium and vilanterol in an industry-sponsored, multicenter trial in which 1500 patients with moderate-to-very severe COPD were randomized to umeclidinium, vilanterol, combination umeclidinium and vilanterol, or placebo for 24 weeks. Half the patients were using inhaled corticosteroids.

Improvements in the primary endpoint of mean change in trough forced expiratory volume in 1 second (FEV₁) were significantly greater with combination therapy than with umeclidinium monotherapy and vilanterol monotherapy (0.08 L and 0.11 L, respectively), as were reductions in symptom scores and rescue albuterol use. Risk for exacerbations was lower in all treatment groups compared with placebo, but was no lower with combination therapy than with monotherapy. Adverse events were similar in all groups.