Clinical Meaningfulness of the Composite Endpoint, COPDCompEx, in Defining Exacerbations and Worsening of COPD: A Post Hoc Analysis of 4 Clinical Interventional Studies of COPD.

PURPOSE: COPDCompEx is a novel composite end point that includes moderate and severe exacerbation events (requiring oral corticosteroid and/or antibiotic use, or hospitalization), as well as acute worsening events (AWEs), defined as deteriorating chronic obstructive pulmonary disease (COPD) symptoms accompanied by a decline in peak expiratory flow (PEF; morning or evening) or an increase in reliever medication use. AWEs are generally self-managed and rarely reported in clinical trials.

PATIENTS AND METHODS: In this post hoc analysis, patient data were obtained from 4 COPD clinical intervention studies and were pooled and grouped according to the occurrence of COPDCompEx events (exacerbations only, AWEs only, and mixed events). For each group, outcomes evaluated included: PEF, reliever medication use, COPD symptoms (ie, breathlessness, sputum, cough, and sleep), forced expiratory volume in 1 second (FEV1), and St. George's Respiratory Questionnaire (SGRQ).

RESULTS: All event types impacted PEF and reliever medication use, with AWEs having a greater effect than exacerbations (event-level data). The COPD symptoms were more pronounced for AWEs and mixed events than exacerbations; the return to baseline was slower for mixed events. Additionally, mixed events had a greater impact on FEV1 and SGRQ scores compared to non-COPDCompEx and other COPDCompEx events (patient-level data), indicating a potential impact on lung function and quality of life.

CONCLUSION: The COPDCompEx composite outcome includes patient-relevant AWEs that represent a clinically meaningful, patient-centric end point. The data highlight the relevance of COPDCompEx as a drug development tool that could improve clinical development in COPD treatments thereby achieving better outcomes for patients.