Rationale: Lung function, health status, and exacerbations are important measures of chronic obstructive pulmonary disease (COPD) progression. So far, treatments in COPD have failed to demonstrate a reduction in rate of decline of trough forced expiratory volume in 1 second (FEV1) or mortality, which may be related to the multicomponent nature of COPD. This post hoc analysis assessed the suitability to predict long-term outcomes using a composite endpoint in patients with moderate to very severe COPD in the UPLIFT trial that may better reflect the multifactorial disease progression in COPD. Methods: In the 4 year UPLIFT study (NCT00144339) Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage 2 – 4 COPD patients were randomized to receive tiotropium 18 µg once daily (via Handihaler®) or placebo. A composite endpoint of clinically important deterioration (CID: first confirmed ≥100mL decrease in FEV1, confirmed increase in St. George's Respiratory Questionnaire (SGRQ) total score of ≥4units, or time to first moderate/severe exacerbation) was tested and treatment arms were pooled. Results: CID events were highly variable across patients. Confirmed FEV1 deterioration and confirmed SGRQ deterioration were observed at the same assessment in only 18% of patients. Time intervals between a first event and subsequent, different, event type were also highly variable. CID events at 6 and 12 months were a good predictor of moderate/severe and severe exacerbation, but a weaker, predictor for death [CID at 6 months HR: 1.21,95% CI: 1.06, 1.39; CID at 12 months HR 1.31, 95% CI: 1.13, 1.53]. When CID events were analyzed as time-varying covariate to predict death, it was associated with a HR of 1.69 [95% CI 1.42, 2.01]. Importantly, tiotropium significantly lowered Hazard ratios for time to first CID in GOLD 2 [HR: 0.70, 95% CI: 0.65, 0.77] and GOLD 3 patients [HR: 0.69, 95% CI: 0.63, 0.75]. Conclusions: Here we show that CID is a clinically meaningful parameter in order to predict long-term outcome in COPD, including mortality. CID may therefore have a significant impact on future clinical trial designs, e.g. by reducing the optimal number of participants to show a clinically relevant effect of therapeutic intervention. CID may also change future treatment strategies by taking into account the multicomponent nature of COPD.
No takes yet. Share an insight, caveat, or question.
Rabe et al. (2018) studied this question.