Bleecker 2016

Methods	Randomised, double‐blind, parallel‐group, placebo‐controlled trial run over 48 weeks
Participants	1204 participants with symptomatic asthma were randomised to 1 of 3 groups (benralizumab 30 mg 4 weeks, benralizumab 30 mg 8 weeks, or placebo) Main inclusion/exclusion criteria: ≥ 2 exacerbations in the previous 12 months ACQ‐6 score ≥ 1.5 at enrolment FEV1 < 80% (if 12‐17 years old, < 90%) maintenance treatment with high‐dose (≥ 500 μg/d FP or equivalent) ICS/LABA for ≥ 12 months for adults > 18 years, or at least medium‐dose (≥ 250 μg/d FP or equivalent) ICS/LABA for children (12‐17 years) Age mean (SD) years: benralizumab 30 mg every 4 weeks, 50 (13.4); benralizumab 30 mg every eight weeks, 48 (14.5); placebo, 49 (14.9) Males (%): benralizumab 30 mg every four weeks, 124 (31%); benralizumab 30 mg every eight weeks, 146 (37%); placebo, 138 (34%) Baseline mean (SD) FEV1 % predicted: benralizumab 30 mg every four weeks, 57 (14.1); benralizumab 30 mg every eight weeks, 56 (14.6); placebo, 57 (15.0) Allocation: benralizumab 30 mg every 4 weeks, 399; benralizumab 30 mg every eight weeks, 398; placebo, 407
Interventions	SC benralizumab 30 mg/mL every 4 weeks or every 8 weeks versus placebo
Outcomes	Primary outcomes Annual asthma exacerbation rate. Secondary outcomes Pre‐bronchodilator FEV1 Total asthma symptom score, Time to first asthma exacerbation Asthma exacerbations associated with visit to ED, urgent care centre or admission to hospital Post‐bronchodilator FEV1 ACQ‐6, AQLQ(S)+12 Blood eosinophils
Notes	Multi‐centre trial in 374 centres from 17 countries Funded by AstraZeneca and Kyowa Hakko Kirin
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Each participant was assigned a unique enrolment number and randomisation code by an interactive web‐based voice response system
Allocation concealment (selection bias)	Low risk	The identity of the treatment allocation was not made available to the participants, investigators involved in participant treatment or clinical assessment, or study funder
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind (participant, caregiver and investigator)
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated, no clarification available from study authors
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawal rates were relatively low (10.1%‐12.8%)
Selective reporting (reporting bias)	Low risk	Unless otherwise specified, all results were presented for participants with baseline blood eosinophilia