Corticosteroid Resistance in Smokers—A Substudy Analysis of the CORTICO-COP Randomised Controlled Trial

Abstract

The CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days; 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days; 95% CI, 7.5–9.9; p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD

“…Another real-world observational study conducted in 1290 Chinese patients admitted for AECOPD found that the hospitalisation time following treatment with systemic corticosteroids was shorter in patients with eosinophilia than patients without eosinophilia with smoking history (median 8 vs 9 days, p=0.046), and the results were similar between the two groups in patients without smoking history (p=0.376) 41. Another substudy analysis of the Corticosteroid Reduction in COPD (CORTICO-COP) RCT showed that smoking status did not influence the role of eosinophils as a biomarker in guiding corticosteroid treatment 19. However, the small sample size (n=318) may have been insufficient to power the statistical analysis.…”

“…41 Another substudy analysis of the Corticosteroid Reduction in COPD (CORTICO-COP) RCT showed that smoking status did not influence the role of eosinophils as a biomarker in guiding corticosteroid treatment. 19 However, the small sample size (n=318) may have been insufficient to power the statistical analysis. Similarly, our study based on a real-world setting observed that regardless of smoking, higher levels of eosinophils reduced the risk of corticosteroid treatment failure.…”

“…One substudy showed that smoking status did not influence the role of eosinophils as a biomarker in guiding corticosteroid treatment. 19 However, the small sample size (n=318) may have been insufficient to power the statistical analysis. Other cohort study has shown the increased exacerbation rate with elevated eosinophil count with stable COPD was restricted to ex-smokers.…”

“…It is currently unknown whether blood eosinophils and smoking are jointly associated with the failure of corticosteroid treatment. One substudy showed that smoking status did not influence the role of eosinophils as a biomarker in guiding corticosteroid treatment 19. However, the small sample size (n=318) may have been insufficient to power the statistical analysis.…”