New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives

Br J Clin Pharmacol. 2015 May;79(5):695-708. doi: 10.1111/bcp.12545.

Abstract

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2 -adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Keywords: COPD; QVA149; bronchodilators; fixed dose combinations; umeclidinium; vilanterol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Dry Powder Inhalers
  • Humans
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Drug Combinations
  • Muscarinic Antagonists