A post-hoc subgroup analysis of data from a six month clinical trial comparing the efficacy and safety of losmapimod in moderate-severe COPD patients with ≤2% and >2% blood eosinophils

Abstract

These findings indicate eosinophil-related heterogeneity within COPD and suggest that losmapimod could be a potential therapy to reduce exacerbations in COPD patients with eosinophil levels ≤2%. This needs to be explored further in a prospectively designed study with pre-specified criteria for blood eosinophil subgroups in COPD patients.

Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD

“…Interestingly, the proportion of patients ⩾2% was similar to that seen in the healthy subjects in the same cohort [6]. The stratification of patients using 2% and ⩾150 cells•µL −1 cut-off values has been justified because this threshold seemed to identify patients more likely to exacerbate in the post hoc analysis of clinical trials [5,[9][10][11]23].…”

Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

“…The activation of p38 MAPK induces inflammatory mediators such as IL-1β, IL-8 and MMP in various inflammatory cells, leading to the exacerbation of COPD symptoms. The inhibition of p38 MAPK showed efficacy in a six month clinical trial in COPD patients with ≤2% blood eosinophils (Marks-Konczalik et al ., 2015). PI3K-mediated signaling in macrophages and neutrophils is involved in inflammation and immune responses and the activity is up-regulated in the lungs of COPD.…”

Biological effects of p38 MAPK inhibitor losmapimod does not translate to clinical benefits in COPD

“…The first clinical study with losmapimod 7.5 mg in moderate COPD showed encouraging results with an 11% reduction in plasma fibrinogen and a signal of improvement in hyperinflation [20]. The following dose-ranging study confirmed the effectiveness of the therapy in reducing fibrinogen levels and showed a dose-related reduction in the rate of moderate/severe exacerbations in a sub-group of subjects with blood eosinophils 2% (post hoc analysis), identifying a possible COPD phenotype who may respond positively to losmapimod therapy [21,22]. This reduction in exacerbation frequency was dose dependent with the largest observed reduction in exacerbation rate being associated with the highest exposure (15 mg twice daily).…”