Health status in the TORCH study of COPD: treatment efficacy and other determinants of change

Paul W Jones, Julie A Anderson, Peter Ma Calverley, Bartolome R Celli, Gary T Ferguson, Christine Jenkins, Julie C Yates, Jørgen Vestbo, Michael D Spencer, TORCH investigators, Paul W Jones, Julie A Anderson, Peter Ma Calverley, Bartolome R Celli, Gary T Ferguson, Christine Jenkins, Julie C Yates, Jørgen Vestbo, Michael D Spencer, TORCH investigators

Abstract

Background: Little is known about factors that determine health status decline in clinical trials of COPD.

Objectives: To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.

Methods: St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.

Measurements and main results: Data from 4951 patients in 28 countries were available. SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains. SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001). There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women. Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1. The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.

Conclusions: In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors. Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.

Trial registration: ClinicalTrials.gov: NCT00268216.

Figures

Figure 1
Figure 1
Plots showing adjusted mean change for the SGRQ Total score (A) and the Symptoms (B), Activity (C) and Impacts (D) domains, over 3 years by treatment group. A lower score indicates better health. The plot for each domain shows the change over time as the left-hand panel (error bars are standard error). The right-hand plots are from a repeated measures analysis of the effects of treatment over the 3 years of the study and are pair-wise comparisons between the treatment arms (error bars are 95% confidence intervals).
Figure 2
Figure 2
Mean change in SGRQ Total score at 3 years by region for patients treated by placebo and SFC. A lower score indicates better health. A test for an interaction between region and treatment effect was not significant (p = 0.16).
Figure 3
Figure 3
Change in SGRQ Total score in patients categorized according to GOLD stage - patients treated with placebo only. *Adjusted for baseline SGRQ, smoking, age, sex, BMI, region, and visit.
Figure 4
Figure 4
Relationship between change in SGRQ Total score over the 3-year study period and change in FEV1 by age category. A negative score indicates improved health. Using analysis of covariance: difference in slopes p = 0.008; difference in intercepts p < 0.0001.
Figure 5
Figure 5
Change in SGRQ Total score in patients treated with placebo. Note: only 55% of patients remained in the study to 156 weeks.

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Source: PubMed

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