Clinical synergism of LABA/LAMA combinations in COPD patients

Abstract

Background: Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) fixed-dose combinations (FDCs) are always more effective than monocomponents in terms of the improvement in trough FEV1 in patients with chronic obstructive pulmonary disease (COPD) [1]. Nevertheless, the clinical interaction between LABAs and LAMAs has been never investigated. Aim: We analyzed the clinical interaction between LABAs and LAMAs in improving dyspnea in COPD patients. Methods: The Bliss Independence approach was applied on the transitional dyspnea index (TDI) effect estimates resulting by a recent synthesis [1]. The observed effect elicited by LABA/LAMA FDCs was compared with the expected additive response obtained by the interaction analysis of the effects induced by LABAs and LAMAs administered as monocomponents. Results are reported as % increase of TDI (±SEM) vs. additive effect. Results: LABA/LAMA FDCs synergistically enhanced TDI (+4.6±0.3%, P Conclusions: This study demonstrates that the interaction between LABAs and LAMAs produced always greater TDI improvement than the expected additive response, leading to clinical synergism. The small extent of synergic interaction supports the hypothesis that the monocompontents are overdosed when administered as FDCs. Reference 1. Calzetta et al., Chest. 2016 May;149(5):1181-96