Rethinking Blood Eosinophils for Assessing ICS Response in COPD: A Post-Hoc Analysis from FLAME

Background The varied treatment response to inhaled corticosteroids (ICS) in COPD, and the increased risk of pneumonia necessitate a personalised ICS approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. This post-hoc analysis evaluates the ability of different BEC measurements to predict ICS treatment response. BEC measured either on or off ICS treatment, and BEC change during ICS treatment were investigated. Methods FLAME, a 52-week, double-blind RCT compared LABA/LAMA versus LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre and post run-in period BEC to represent BEC on and off ICS, respectively. In this post-hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS containing regimen. Results Our study confirms that LABA/LAMA combination is superior, or at least non-inferior, to LABA/ICS in curbing exacerbations for most FLAME participants. Lower BEC off and BEC on ICS and lack of significant BEC suppression during ICS treatment corresponded to superior response to LABA/LAMA in terms of exacerbation rate, time-to-first exacerbation, and time-to-first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment, and higher BEC on ICS did not predict ICS treatment response. For these patients BEC off ICS and BEC change proved more predictive. Conclusion This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response. What is already known on this topic Blood eosinophil count (BEC) is used to guide the administration of inhaled corticosteroids (ICS) for COPD, but they may be suppressed in response to systemic or inhaled corticosteroids. What this study adds This post-hoc analysis suggests that BEC change during treatment with ICS and this change is associated with treatment response to ICS containing regimens. More specifically, BEC suppression is associated with favourable response to ICS, while unchanged or increased BEC is associated with inferior ICS treatment effect and increased risk of pneumonia. In 9% of participants, BEC changes significantly (≥200 cells/μL) during ICS treatment, and in these patients, BEC on ICS is not reliable in predicting treatment response to ICS, as it appears that some ICS responders may actually have low BEC on ICS and vice versa. How this study might affect research, practice or policy These findings highlight the potential utility of BEC change during ICS treatment as a predictive biomarker of treatment response to ICS and question the use of BEC on ICS to guide withdrawal of ICS, but need prospective validation.