Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies

Taking the red out of eosinophilic inflammation in COPD

“…This post hoc analysis by Criner et al 11 provides the basis for a prospective controlled trial to confirm that the identified criteria for the reduction of COPD exacerbation with benralizumab are valid. Using these criteria, a clinical study is currently underway that aims to recruit 868 patients with moderate to very severe COPD who have 2 or more exacerbations per year in spite of triple therapy and peripheral blood eosinophilia (>300/mL) in a randomized trial of benralizumab at 100 mg every 3 weeks versus placebo.…”

“…Clearly, appropriate study design and careful patient selection will be critical to determine whether targeting eosinophilic inflammation in COPD is beneficial. Despite the disappointing results of the initial benralizumab reports, Criner et al 11 conducted a post hoc analysis using data from the original study and pooled results from the GALATHEA and TERRANOVA trials with the intent of identifying clinical and physiological characteristics of patients with COPD who would benefit from benralizumab therapy. The study subjects were aged 40 to 85 years and had moderate to severe airflow obstruction, elevated blood eosinophil levels, and at least 2 exacerbations or 1 severe exacerbation in spite of dual (ICS 1 LABA or LABA 1 LAMA) or triple therapy (ICS 1 LABA 1 LAMA).…”

“…The primary end point was a reduction in annual exacerbation rate from benralizumab versus placebo. 11 From the 2665 potential candidates with baseline blood eosinophil counts (> _220/mL), 3 or more exacerbations per year despite triple therapy, postbronchodilator FEV 1 less than or equal to 40%, and postbronchodilator response greater than or equal to 15% were identified candidates most likely to benefit from benralizumab 100 mg every 8 weeks versus placebo (relative risk, 0.70; 95% CI, 0.56-0.88]). 11 Inclusion of total serum IgE levels and the presence of aeroallergen sensitization would have been of interest as additional potential biomarkers, but they were not reported.…”

Blood Eosinophil Counts in Chronic Obstructive Pulmonary Disease: A Biomarker of Inhaled Corticosteroid Effects

“…RCTs investigating the effects of monoclonal antibodies targeting IL-5, conducted in COPD patients with a history of exacerbations, have reported both positive and negative results for the effect on exacerbation rate reduction [ 67 , 68 ]. A prespecified combined analyses of the GALATHEA and TERRANOVA studies of benralizumab (which targets IL-5 receptor alpha) demonstrated that the greatest treatment benefit was observed in the subgroup receiving triple therapy with blood eosinophil counts ≥220 cells/µL and ≥3 exacerbations in the prior year [ 69 ]. These findings highlight that significant eosinophilic inflammation, which may respond to monoclonal antibody targeting, can persist despite ICS treatment.…”

The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians

“…Though not surprising, this evidence identifies the population (phenotype) where the efficacy of an anti-IL5 should be expected: those patients with exacerbations not requiring antibiotics that more likely have eosinophilic exacerbations [69]. The results with anti-IL5Ra in COPD are overall less convincing [70]. However, subgroup analyses are being conducted to identify the population that could benefit from anti-IL5Ra treatment.…”