Background Most COPD patients will deteriorate over time, so a key aim of COPD management is to minimise this risk. We developed a composite endpoint of three aspects of worsening: COPD exacerbations, clinically important deteriorations (CID) in lung function and health status. This method was applied in a post hoc analysis of TORCH, a 3-year, double-blind, placebo-controlled trial in moderate/severe COPD that compared salmeterol 50 mcg/fluticasone proprionate 500 mcg combination (SFC) with placebo (PBO), salmeterol 50 mcg (SAL) alone and fluticasone 500 mcg alone. In this analysis, SFC was compared with SAL to test whether the addition of inhaled corticosteroids (ICS) reduced the risk of a CID beyond their known effect on exacerbations.
Method The overall analysis was performed in 6112 patients, 3054 treated with SFC and SAL. A CID was defined as a decrease ≥100 mL in post-bronchodilator FEV1, an increase (worsening) in St George’s Respiratory Questionnaire (SGRQ) total score of ≥4 units, or an on-treatment moderate/severe exacerbation. The time to the first deterioration of each component and the composite endpoint was analysed using a Cox’s proportional hazards model with covariates of: treatment, smoking status and geographical region; baseline values for FEV1 and SGRQ score were included for those individual component endpoints. The analysis was performed on the intention-to-treat (ITT) population and in patient categorised into GOLD grades I/II and III/IV.
Results A similar percentage of patients in both treatment groups eventually experienced ≥1 category of deterioration during the 3-year trial. The Hazard Ratios (HR) show that compared to SAL, SFC significantly reduced the time to first worsening of FEV1 and SGRQ (Table 1). The benefit of SFC over SAL was seen with the composite endpoint in the ITT population and both GOLD subgroups.
Conclusion This post hoc analysis showed that, although most patients eventually experienced one of the three measures of deterioration, SFC significantly reduced the risk of a first composite CID compared to SAL. This added benefit of ICS was equally present in patients with mild/moderate or severe/very severe COPD.