Dual versus monotherapy with bronchodilators in GOLD group B COPD patients according to baseline FEV1 level: a patient-level pooled analysis of phase-3 randomized clinical trials

Jieun Kang,Sei Won Lee,Yeon-Mok Oh,Jae Seung Lee,Jung Bok Lee

doi:10.1186/s12931-021-01648-5

Abstract

BackgroundWhich patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment.MethodsThis was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV1, the St. George’s Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events.ResultsA total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV1, reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group.ConclusionsDual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV1 than those with higher FEV1.

Highlights

Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary dis‐ ease (COPD) is only loosely defined
The importance of Forced expiratory volume in 1 s (FEV1) is acknowledged, it does not determine treatment according to the Global initiative for Chronic Obstructive Lung Disease (GOLD) document [4]
We evaluated whether the efficacy of dual versus monotherapy differs between these two groups on the following outcomes: change in the trough FEV1, change in the St. George’s Respiratory Questionnaire (SGRQ) total score, the proportion of SGRQ responders, time to first exacerbation, and the risk of adverse events

Summary

Introduction

Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary dis‐ ease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a popu‐ lation more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. Chronic obstructive pulmonary disease (COPD) is one of the major causes of chronic morbidity and mortality worldwide [1,2,3]. It is characterized by irreversible airflow limitation and respiratory symptoms such as cough, sputum, and dyspnea [4]. GOLD recommends dual therapy as an initial treatment only in patients with severe symptoms [6]

Methods

Results

Conclusion