Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

Abstract

Objective: We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.

Methods: Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57-75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.

Results: For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.

Discussion: Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.

Keywords: COPD Exacerbations.

Figure 1

Proportion of all patients with baseline blood eosinophil level <2% and ≥2% in ≥1-year studies of fluticasone propionate (FP)/salmeterol (SAL) in patients with COPD.

Figure 2

Percentage reduction in moderate/severe exacerbation rates with fluticasone propionate (FP)/salmeterol (SAL) and monocomponents for treatment comparisons of interest in ≥1-year studies by percentage baseline blood eosinophil level in (A) INSPIRE, (B) TRISTAN and (C) SCO30002. Analysis performed using a negative binomial regression model with covariates of either treatment, gender, history of exacerbations, baseline % predicted FEV₁, percentage eosinophil group and treatment by percentage eosinophils interaction or treatment, gender, baseline % predicted FEV₁, percentage eosinophil group and treatment by percentage eosinophils interaction. <1 favours FP or FP/SAL; >1 favours tiotropium/placebo. Note: statistically significant comparisons (p<0.05) shown in bold font.

Figure 3

Percentage reduction in moderate/severe exacerbation rates with fluticasone propionate (FP)/salmeterol (SAL) and monocomponents for treatment comparisons of interest in ≥1-year studies by absolute baseline blood eosinophil count in (A) INSPIRE, (B) TRISTAN and (C) SCO30002. Analysis performed using a negative binomial regression model with covariates of either treatment, gender, history of exacerbations, baseline % predicted FEV₁, percentage eosinophil group and treatment by percentage eosinophils interaction or treatment, gender, baseline % predicted FEV₁, percentage eosinophil group and treatment by percentage eosinophils interaction.