BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with 
eosinophilic airway inflammation in 10-20% of patients. Benralizumab, an 
anti-interleukin-5 receptor α monoclonal antibody, depletes blood and sputum 
eosinophils. We aimed to establish whether benralizumab reduces acute 
exacerbations of COPD in patients with eosinophilia and COPD.
METHODS: We did this randomised, double-blind, placebo-controlled, phase 2a 
study between Nov 18, 2010, and July 13, 2013, at 26 sites in the UK, Poland, 
Germany, Canada, the USA, Denmark, and Spain. Adults aged 40-85 years, with 
moderate-to-severe COPD, at least one acute exacerbation of COPD, and a sputum 
eosinophil count of 3·0% or more within the previous year, were randomly 
assigned (1:1) via computer-generated permuted block randomisation (block size 
of four), with an interactive voice or web-response system, to receive placebo 
or 100 mg benralizumab subcutaneously, every 4 weeks (three doses), then every 8 
weeks (five doses) over 48 weeks. Study site personnel included in study 
assessments, participants, and data analysts, were masked to treatment 
allocation. The primary endpoint was the annualised rate of acute exacerbations 
of COPD at week 56, defined as the number of acute exacerbations divided by 
total duration of person-year follow-up. Secondary and exploratory endpoints 
included COPD-specific Saint George's Respiratory Questionnaire (SGRQ-C), 
Chronic Respiratory Questionnaire self-administered standardised format 
(CRQ-SAS), pre-bronchodilator forced expiratory volume in 1 second (FEV1), and 
safety. We did a prespecified subgroup analysis by baseline blood eosinophil 
count. Analyses were by intention to treat and per-protocol. This trial is 
registered with ClinicalTrials.gov, number NCT01227278.
FINDINGS: We randomly assigned 101 patients to receive placebo (n=50) or 
benralizumab (n=51), of whom 88 (87%) patients completed the study. Six patients 
who completed the study were excluded from the per-protocol population because 
of major protocol violations; the per-protocol population thus included 82 
patients. Benralizumab did not reduce the annualised rate of acute exacerbations 
of COPD compared with placebo in the per-protocol population, with rates of 0·95 
(0·68-1·29; n=40) versus 0·92 (0·67-1·25; n=42). Mean pre-bronchodilator FEV1 
change from baseline to week 56 was -0·06 L (SD 0·24) with placebo, and 0·13 L 
(0·41) with benralizumab (p=0·014). Numerical, albeit non-significant, 
improvement in acute exacerbations of COPD, SGRQ-C, CRQ-SAS, and FEV1 were 
greater in benralizumab-treated patients with baseline blood eosinophil 
concentrations of 200 cells per μL or more or 300 cells per μL or more. 
Incidence of treatment-emergent adverse events was similar between the two 
groups, with the most common events being respiratory disorders (31 [62%] of 50 
patients given placebo vs 32 [63%] of 51 given benralizumab) and infections (28 
[56%] vs 27 [53%]). A higher incidence of serious treatment-emergent adverse 
events were recorded in patients in the benralizumab group than in those in the 
placebo group (14 vs nine patients), although none of these events were 
considered by the investigator to be benralizumab related.
INTERPRETATION: Compared with placebo, benralizumab did not reduce the rate of 
acute exacerbations of COPD. However, the results of prespecified subgroup 
analysis support further investigation of benralizumab in patients with COPD and 
eosinophilia.
FUNDING: MedImmune.