Abstract Rationale Patients with COPD may continue to experience frequent exacerbations, high symptom burden and increased mortality risk while receiving inhaled triple therapy (TT). This study compared clinical outcomes and characteristics of frequently and infrequently exacerbating patients treated with TT in real-world clinical practice from the United States. Methods A retrospective cohort study of people aged ≥40-years with a physician-assigned COPD diagnosis and ≥2 prescriptions or ≥ 90 days of TT (Jul2021-Jun2024) was conducted using the IQVIA PharMetrics US claims database. Patients with frequent exacerbations (FE: ≥1 severe or ≥ 2 moderate within 12-months) while on TT were compared to patients with similar levels of TT exposure who had not yet experienced frequent exacerbations (infrequent exacerbators IE). Patients were matched 1:1 using index date (+/-30d), and TT exposure (duration and type). Patients had 12-months baseline history and were followed for a minimum of 30-days. Baseline and follow-up characteristics were assessed; incidence rates (IRs) for moderate/severe exacerbations, cardiopulmonary events and mortality (per 100-patient-years PYs) were calculated. Sensitivity analysis was conducted excluding those patients without baseline asthma diagnosis (COPD-only). Results A total of 82,478 patients were identified (41,617 FE, 40,861 IE) and followed for mean 492 days. Mean age was similar (FE: 64.2 vs. IE: 64.6) and more frequent exacerbators were female (61.0% vs. 56.4%). While general comorbidity was similar, FE patients had greater baseline history of acute respiratory failure (43.5% vs. 27.3%), anxiety (40.2% vs. 35.0%), chest pain (42.3% vs. 33.1%), cough (47.7% vs. 35.6%) and dyspnea (71.8% vs. 58.5%) vs. IE patients. Incidence rate of exacerbations during follow-up was 44% greater for FE (112.9/100PYs 112.0-113.8) vs. IE (78.3/100PYs 77.6-79.1) Table. Cardiopulmonary events (22.1 21.7-22.5 vs. 13.2 12.9-13.5) and mortality (5.1 4.9-5.3 vs. 4.1 3.9-4.3) were 67.4% and 25.6% greater among the FE patients, including cardiovascular events. Cumulative incidence in the first year of follow up were 64.9% vs. 51.6% for exacerbations, and 22.1% vs. 13.3%, for cardiopulmonary events for FE and IE, respectively. Event rates were consistent within the COPD-only analyses (exacerbations: 111.7 110.6-112.7 vs. 78.7 77.8-79.6, cardiopulmonary: 22.3 21.7-22.8 vs. 13.3 12.9, 13.7). Conclusions Patients identified as frequent exacerbators while on TT represent an identifiable high-risk subgroup with noticeably higher disease burden and symptoms, and consistently greater rates of exacerbations, cardiopulmonary and mortality outcomes during follow-up. There is a need for proactive identification of patients who frequently exacerbate while on triple therapy and the consideration of new treatment options for these patients. This abstract is funded by: AstraZeneca
Pollack et al. (2026) studied this question.