Inhaled corticosteroids (ICS) are an important treatment for COPD. Exacerbations, defined as acute worsening of symptoms necessitating treatment with antibiotics and/or systemic corticosteroids or hospitalisation, are a key determinant of COPD morbidity, mortality and healthcare costs. Compared with placebo, ICS such as fluticasone propionate (FP) and budesonide reduce exacerbations by up to 20% as monotherapy, and up to 30% in combination with a long-acting β2-agonist (LABA). National and international guidelines on the management of COPD recommend that patients with COPD at risk of exacerbations receive ICS/LABA maintenance therapy.
The TOwards a Revolution in COPD Health (TORCH) study showed that ICS treatment was associated with an increased risk of non-fatal pneumonia in patients with FP-treated COPD, now recognised as an ICS class effect. The reconsideration of potential risks associated with ICS treatment, weighed against its known benefits, has motivated the search for biomarkers to inform COPD treatment decisions.
A predictive marker for ICS (or ICS/LABA) effectiveness in preventing COPD exacerbations could aid clinical decision-making by identifying patients likely to gain the most benefit from ICS-based treatment. Blood eosinophil count may provide such a marker. Studies have demonstrated associations between airway eosinophilia and exacerbations of chronic bronchitis and COPD. Exacerbations are heterogeneous, presenting as one of four distinct phenotypes, and airway eosinophilia in the stable state was found to be predictive of subsequent exacerbation phenotype. Relationships between sputum eosinophilia and steroid responsiveness in COPD have also been reported. The use of systemic corticosteroids in patients experiencing acute exacerbations of COPD has shown greater benefit in patients with a blood eosinophil level of ≥2% versus those with <2%. There is also evidence for an association between airway eosinophilia with response to systemic corticosteroids for FEV1 and quality of life. A recent retrospective analysis of data from two parallel 1-year studies of once-daily ICS/LABA, fluticasone furoate (FF)/vilanterol (VI) in patients with moderate-to-very severe COPD showed a greater reduction of moderate and severe exacerbations in patients with a blood eosinophil level ≥2% vs <2% when treated with FF/VI compared with VI alone.
To investigate the potential of blood eosinophil level as a marker for the preventive efficacy of ICS or ICS/LABA on exacerbations, the team reanalysed data from studies comparing ICS or ICS/LABA combination therapy (FP/salmeterol (SAL)) with a long-acting antimuscarinic (LAMA), LABA or placebo according to baseline eosinophil categories.
The findings were as follows:
Objective: We performed a review of studies offluticasone 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.
To read the study in its entirety:
http://thorax.bmj.com/content/early/2015/11/19/thoraxjnl-2015-207021.abstract
