A16-10 Defining Disease Stability in COPD: A Post-Hoc Analysis of the Phase III IMPACT Trial

Rationale

Disease stability (DS), which reflects a state of low disease activity over time (i.e., no exacerbations, no worsening of symptoms, and no accelerated loss of lung function), is an ambitious, achievable COPD treatment target that is included in the 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report. This analysis aimed to describe DS using post-hoc analyses of Phase III data.

Methods

This post-hoc analysis used data up to Week 52 of the IMPACT trial (NCT02164513; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] vs FF/VI or UMEC/VI). DS was defined as a three-component composite of no moderate/severe exacerbations and no worsening (including any improvement) of COPD Assessment Test (CAT) score and trough FEV1. Recognizing that spirometry is not always available, a two-component composite (exacerbations and CAT; DS-2) was also evaluated alongside the full DS composite. DS components were also assessed individually, including in patients who were exacerbation-free since baseline, patients with no worsening in CAT or FEV1 since baseline, and patients who achieved improvements from baseline of at least the established minimal clinically important difference (MCID) in CAT (improvement ≥2 units) or FEV1 (improvement ≥100 mL). Results were primarily descriptive in nature, with adjusted risk ratios (aRRs) and confidence intervals (CI) generated using a log-binomial model.

Results

At Week 52 (N = 10,355), DS was achieved by 22% (FF/UMEC/VI; n = 896/4151), 14% (FF/VI; n = 578/4134), and 16% (UMEC/VI; n = 330/2070) of patients; patients were more likely to achieve DS with FF/UMEC/VI versus FF/VI (aRR: 1.53; 95% CI: 1.39, 1.68) and versus UMEC/VI (aRR: 1.36; 95% CI: 1.21, 1.52) (Figure). More patients achieved the DS-2 composite (FF/UMEC/VI: 28%; FF/VI: 24%; UMEC/VI: 25%) than the full DS composite. Individually, approximately half of patients were exacerbation-free at Week 52 and, among patients with no worsening from baseline in CAT and FEV1, most patients experienced improvements exceeding the MCID.

Conclusions

DS is achievable in a meaningful proportion of this patient population, is more likely to be achieved with triple versus dual therapy, reflects the contributions of all three components, and in many cases, represents clinically meaningful improvements in exacerbations, health status, and lung function versus baseline. DS may be assessed in the absence of spirometry; however, where possible all three components should be evaluated. Regular assessment of DS may help bolster confidence in current treatment effectiveness or identify patients needing treatment optimization.

This abstract is funded by: GSK (116855)