DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach

Abstract

Introduction: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD.

Methods: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV₁) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV₁ and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta₂-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age.

Results: Model-predicted decline in FEV₁ showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively.

Conclusions: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Keywords: COPD exacerbation; Chronic obstructive pulmonary disease (COPD); Dual bronchodilator therapy (LAMA/LABA); GOLD grades; Lung function decline; Triple therapy (ICS/LAMA/LABA).