Long-term outcomes following first short-term clinically important deterioration in COPD

Ian P Naya, Lee Tombs, Hana Muellerova, Christopher Compton, Paul W Jones, Ian P Naya, Lee Tombs, Hana Muellerova, Christopher Compton, Paul W Jones

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline. Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed. We evaluated post hoc the link between early CID and long-term adverse outcomes.

Methods: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George's Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies. Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE). Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.

Results: In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+. At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001). Similar risks post-CID were observed in ECLIPSE.

Conclusions: A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.

Trial registration: NCT00268216 ; NCT00292552 .

Keywords: COPD; Clinically important deterioration; Composite measures; Mortality.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Competing interests

IPN, HM, CC, and PWJ are employees of GSK and hold GSK stocks/shares. LT is a contingent worker at GSK.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Proportions of patients experiencing CIDs in the TORCH study. CID, clinically important deterioration; CID+, presence of a CID within 6 months of enrollment into the study; CID-, absence of a CID within 6 months of enrollment into the study; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; SGRQ, St George’s Respiratory Questionnaire; TORCH, TOwards a Revolution in COPD Health
Fig. 2
Fig. 2
LS mean change from baseline in (a) FEV1 (mL) and (b) SGRQ score over time based on CID status (TORCH study ITT population), CI, confidence interval; CID, clinically important deterioration; CID+, presence of a CID within 6 months of enrollment into the study; CID-, absence of a CID within 6 months of enrollment into the study; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; SGRQ, St George’s Respiratory Questionnaire; TORCH, TOwards a Revolution in COPD Health
Fig. 3
Fig. 3
Time to first (a) moderate/severe exacerbation, (b) exacerbation requiring hospitalization, and (c) all-cause mortality, based on CID status (TORCH study; ITT population). CI, confidence interval; CID, clinically important deterioration; CID+, presence of a CID within 6 months of enrollment into the study; CID-, absence of a CID within 6 months of enrollment into the study; ITT, intent-to-treat; TORCH, TOwards a Revolution in COPD Health
Fig. 4
Fig. 4
All-cause mortality hazard ratios of single CID events and composite CID events for CID+ patients versus CID- patients (TORCH study; ITT population). *Proportion of patients with the specified CID in the first 6 months. CI, confidence interval; CID, clinically important deterioration; CID+, presence of a CID within 6 months of enrollment into the study; CID-, absence of a CID within 6 months of enrollment into the study; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; ITT, intent-to-treat; SGRQ, St George’s Respiratory Questionnaire; TORCH, TOwards a Revolution in COPD Health
Fig. 5
Fig. 5
LS mean change from baseline in (a) FEV1 (mL) and (b) SGRQ score over time based on CID status (ECLIPSE study). CI, confidence interval; CID, clinically important deterioration; CID+, presence of a CID within 12 months of enrollment into the study; CID-, absence of a CID within 12 months of enrollment into the study; COPD, chronic obstructive pulmonary disease; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points; FEV1, forced expiratory volume in 1 s; LS, least squares; SGRQ, St George’s Respiratory Questionnaire
Fig. 6
Fig. 6
Time to first (a) moderate/severe exacerbation, b exacerbation requiring hospitalization, and (c) all-cause mortality, based on CID status (ECLIPSE study). CID, clinically important deterioration; CID+, presence of a CID within 12 months of enrollment into the study; CID-, absence of a CID within 12 months of enrollment into the study; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points

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