Comparative Effectiveness and Safety of LAMA-LABA Inhalers in Chronic Obstructive Pulmonary Disease.

Abstract

Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) is recommended for most patients with symptomatic chronic obstructive pulmonary disease (COPD). Fixed-dose LAMA-LABA therapies are available in metered-dose, dry powder, and soft mist inhalers. However, metered-dosed inhalers are associated with greater greenhouse gas emissions than either dry powder or soft mist inhalers, and questions persist about potential intraclass differences among LAMA-LABAs given variability in their active ingredients, dosing schedules, and delivery devices. To evaluate the comparative effectiveness and safety of once-daily umeclidinium-vilanterol dry powder inhalers, twice-daily glycopyrrolate-formoterol metered-dosed inhalers, and once-daily tiotropium-olodaterol soft mist inhalers. This observational active-comparator study analyzed claims of patients (≥40 years) newly treated with LAMA-LABA inhalers and continuously enrolled in a large commercial health insurance or Medicare Advantage plan during the 183-day baseline period. Patients were propensity score matched 1:1 into 3 cohorts with index dates ranging from May 1, 2016, to February 28, 2025. Data were analyzed from July to August 2025. Patients treated with umeclidinium-vilanterol, glycopyrrolate-formoterol, or tiotropium-olodaterol fixed-dose inhalers. Time to the first moderate or severe COPD exacerbation, major adverse cardiovascular event, urinary tract infection, and pneumonia hospitalization. The cohorts included 9479 matched pairs of patients receiving umeclidinium-vilanterol vs glycopyrrolate-formoterol (mean age, 68.9 [SD, 9.0] years; 10 319 women [54.4%]; 8636 men [45.6%]), 9598 receiving tiotropium-olodaterol vs glycopyrrolate-formoterol (mean age, 69.2 [SD, 8.7] years; 10 513 women [54.8%]; 8680 men [45.2%]), and 36 740 receiving umeclidinium-vilanterol vs tiotropium-olodaterol (mean age, 71.5 [SD, 8.4] years; 39 429 women [53.7%]; 34 044 men [46.3%]). Umeclidinium-vilanterol was associated with a 14% lower hazard of a first moderate or severe COPD exacerbation than glycopyrrolate-formoterol (hazard ratio [HR], 0.86; 95% CI, 0.81-0.91; number needed to treat [NNT], 17) and was associated with a 3% lower hazard than tiotropium-olodaterol (HR, 0.97; 95% CI, 0.94-0.99; NNT, 100). Tiotropium-olodaterol was associated with a 6% lower hazard of a first moderate or severe COPD exacerbation than glycopyrrolate-formoterol (HR, 0.94; 95% CI, 0.89-1.00). Similar risks of first major adverse cardiovascular event, urinary tract infection, and pneumonia hospitalization were observed among patients in all 3 cohorts. This cohort study found that umeclidinium-vilanterol was associated with improved clinical outcomes compared with glycopyrrolate-formoterol and tiotropium-olodaterol. Patients, prescribers, and health systems may consider once-daily umeclidinium-vilanterol dry powder inhalers over alternatives among new users of LAMA-LABA therapy.