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

• Published in: The Lancet Respiratory Medicine
• Main Authors: Criner, Gerard J, Celli, Bartolome R, Singh, Dave, Agusti, Alvar, Papi, Alberto, Jison, Maria, Makulova, Natalya, Shih, Vivian H, Brooks, Laura, Barker, Peter, Martin, Ubaldo J, Newbold, Paul
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2020
• Subjects: COPD; severe exacerbation; benralizumab; Terranova
• Online Access: http://hdl.handle.net/11392/2414456; https://doi.org/10.1016/S2213-2600(19)30338-8; https://www.sciencedirect.com/science/article/abs/pii/S2213260019303388

Background Benralizumab did not significantly reduce exacerbations compared with placebo in the phase 3 GALATHEA and TERRANOVA trials of benralizumab for patients with chronic obstructive pulmonary disease (COPD). We aimed to identify clinical and physiological characteristics of patients with COPD that could help to identify people who are likely to have the greatest treatment effect with benralizumab. Methods We analysed individual study and pooled results from GALATHEA and TERRANOVA. At study enrolment, patients from GALATHEA and TERRANOVA were aged 40-85 years, had moderate to very severe airflow limitation, had elevated blood eosinophil counts, and at least two exacerbations or one severe exacerbation in the previous year despite dual inhaled therapy (inhaled corticosteroids plus long-acting beta(2)-agonists or long-acting beta 2-agonists plus long-acting muscarinic antagonists) or triple inhaled therapy (inhaled corticosteroids plus long-acting beta 2-agonists plus long-acting muscarinic antagonists). We analysed data for 3910 patients who received benralizumab (30 mg or 100 mg subcutaneously every 8 weeks; first three doses every 4 weeks) or placebo with dual or triple therapy to identify factors consistently associated with annual exacerbation rate reduction. We evaluated the annual exacerbation rate for benralizumab versus placebo as the primary endpoint. GALATHEA and TERRANOVA are registered with ClinicalTrials.gov, NCT02138916 and NCT02155660, respectively. Findings For 2665 patients with elevated blood eosinophil counts, treatment effect with benralizumab every 8 weeks at 100 mg, but not at 30 mg, occurred for patients with a history of more frequent exacerbations, poorer baseline lung function, or greater baseline lung function improvement with short-acting bronchodilators. Patients with baseline blood eosinophil counts of 220 cells per mu L or greater with: three or more exacerbations in the previous year receiving benralizumab every 8 weeks versus placebo, had rate ratios (RRs) of 0.69 (95% CI ...