Work

Tiotropium and clinically important deterioration in mild-to-moderate chronic obstructive pulmonary disease: a post hoc win ratio analysis of the Tie-COPD study

Year: 2026

Type: article

Abstract: Background Clinically important deterioration (CID) has been used to assess chronic obstructive pulmonary disease (COPD) progression by time-to-first-event analysis. However, this does not reveal the clinical importance of the CID components. The win ratio may provide a complementary assessment by comparing outcomes according to a prespecified hierarchy. We reanalysed data from the Tie-COPD studywith win ratio to assess the overall treatment benefit associated with tiotropium in patients with mild-to-moderate COPD.Methods In this exploratory post hoc study, the unmatched win ratio method was applied to the outcomes observed in the Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD over 24 months. CID was defined as an occurrence of moderate-to-severe exacerbation, an increase of ≥2 units in COPD Assessment Test (CAT) score or a decrease of ≥100 mL in the forced expiratory volume in 1 s (FEV 1). We evaluated the win ratio across all possible hierarchies of CID components. Exploratory inverse-probability-of-censoring weighted (IPCW), and covariate-adjusted IPCW (CovIPCW) analyses were performed to account for censoring. Subgroup analyses were performed with stratification by sex, smoking status, Global Initiative for Chronic Obstructive Lung Disease stage, CAT score and modified Medical Research Council score at baseline.Results Of the 841 randomised patients, 771 were included in the full analysis set (tiotropium=388; placebo=383). With the clinical hierarchy of CID defined by FEV 1, exacerbation and CAT, the win ratio was 2.26 (95% CI 1.87 to 2.73, p<0.001), and the net benefit was 0.35 (95% CI 0.27 to 0.44, p<0.001). Win ratios were greater than 1 across all hierarchies, subgroups and censoring-adjusted analyses. No treatment-by-subgroup interaction was detected (all p for interaction >0.05).Conclusions In this exploratory post hoc analysis, tiotropium was associated with a greater overall treatment benefit than placebo in patients with mild-to-moderate COPD. This benefit was also observed in patients with mild disease or fewer respiratory symptoms. The direction of the findings was consistent across alternative CID hierarchies and censoring-adjusted analyses.Trial registration number NCT01455129.

Source: BMJ Open Respiratory Research

DOI: 10.1136/bmjresp-2026-004310