Initial treatment of COPD with LABA-ICS or LABA-LAMA: real-world comparative effectiveness.

BACKGROUND: The 2023 Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations advocate long-acting beta2 agonist (LABA) and long-acting muscarinic antagonist (LAMA) combinations (LABA-LAMA) for the initial pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD) with multiple exacerbations. However, this choice, rather than combinations of LABA and inhaled corticosteroids (LABA-ICS), no longer recommended in GOLD, was based on randomised trials that excluded patients with multiple prior exacerbations. RESEARCH QUESTION: What is the comparative effectiveness of initiating COPD treatment with LABA-ICS versus LABA-LAMA inhalers, particularly in patients with multiple COPD exacerbations, in a real-world clinical practice setting? STUDY DESIGN AND METHODS: We identified a cohort of patients with COPD, 40 years of age or older, from the United Kingdom's Clinical Practice Research Datalink. Treatment-naïve initiators of single-inhaler LABA-ICS or LABA-LAMA, with no prior asthma, LABA, LAMA or ICS use, were compared on the incidence of moderate or severe COPD exacerbation over 1 year, after adjustment by propensity score weighting. RESULTS: The study cohort included 20 750 initiators of LABA-ICS inhalers and 16 594 of LABA-LAMA. The overall adjusted HR of a first moderate or severe exacerbation with LABA-ICS relative to LABA-LAMA was 1.03 (95% CI 0.98 to 1.08). Among patients with two or more prior exacerbations, the HR of exacerbation with LABA-ICS versus LABA-LAMA was 0.89 (95% CI 0.81 to 0.97), while it was 1.07 (95% CI 1.00 to 1.15) among patients with no prior exacerbations. The HR was 0.92 (95% CI 0.86 to 0.99) among those with forced expiratory volume in 1 s (FEV1)≥50% predicted. INTERPRETATION: In a real-world clinical practice setting of COPD treatment, initiating therapy with LABA-ICS inhalers may be more effective than LABA-LAMA inhalers among patients with multiple exacerbations, particularly those with FEV1≥50% predicted, but less effective among those with no prior exacerbations and FEV1<50% predicted. This study supports a targeted approach to initial therapy for COPD. .