Delaying disease progression in COPD with early escalation to triple therapy: a modelling study (DEPICT-2).

Introduction: In patients with COPD, dual bronchodilator (long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA)) and triple therapy (inhaled corticosteroid/LAMA/LABA) reduce the risk of exacerbations and lung function decline in the short-mid-term, but their long-term impact is unknown. This modelling study explores long-term impact of these therapies on lung function decline, quality of life (QoL) and all-cause mortality.

Methods: This modelling approach used a longitudinal nonparametric superposition model using published data regarding exacerbations, QoL (assessed by St George's Respiratory Questionnaire (SGRQ)) and mortality. The model simulated disease progression from 40 to 75 years of age and assessed the impact of initiating dual bronchodilator at age 45 years ("LAMA/LABA only" group) and escalation to triple therapy at age 50 years ("Escalation to triple" group) on forced expiratory volume in 1 s (FEV₁) decline, QoL and mortality.

Results: Model simulation predicted that by 75 years of age, "LAMA/LABA only" preserves 159.1 mL of FEV₁ versus no treatment, while "Escalation to triple" preserves an additional 376.5 mL and 217.3 mL of FEV₁ versus no pharmacotherapy and "LAMA/LABA only", respectively. In "LAMA/LABA only", the SGRQ score reduces (-3.2) versus no treatment, which further reduces to -7.5 in "Escalation to triple". In "LAMA/LABA only", mortality reduces by 5.4% by 75 years versus no treatment, while the "Escalation to triple" shows further decrease in mortality by 12.0%.

Conclusion: Early pharmacotherapy initiation and escalation from dual bronchodilator to triple therapy could slow disease progression by preserving lung function and improving QoL and survival in patients with COPD.