Study characteristics |
Methods |
Multicentre, randomised, double‐blind, parallel‐group, placebo‐controlled study |
Participants |
1306 participants with moderate‐severe (medium‐high‐dose ICS + LABA, ≥ 2 asthma exacerbations last 12 months, FEV1 < 80% predicted), ACQ‐6 ≥ 1.5 at enrolment
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Main inclusion/exclusion criteria:
≥ 2 exacerbations in the previous 12 months
ACQ‐6 score ≥ 1.5 at enrolment
FEV1 < 80%
maintenance treatment with medium‐ (≥ 250 μg/day FP or equivalent) to high‐dose (≥ 500 μg/day FP or equivalent) ICS/LABA for ≥ 12 months; high‐dose ICS/LABA for ≥ 3 months
Age mean, years (SD): eosinophil ≥ 300 cells/μL benralizumab 30 mg every 4 weeks, 50 (13.1); eosinophil ≥ 300 cells/μL benralizumab 30 mg every 8 weeks. 50 (13.0); eosinophil ≥ 300 cells/μL placebo, 49 (14.1); eosinophil < 300 cells/μL benralizumab 30 mg every 4 weeks, 52 (12.2); eosinophil < 300 cells/μL benralizumab 30 mg every 8 weeks, 51 (13.8); eosinophil < 300 cells/μL placebo, 52 (14.4)
Male, n (%): eosinophil ≥ 300 cells/μL benralizumab 30 mg every 4 weeks, 82 (34); eosinophil ≥ 300 cells/μL benralizumab 30 mg every 8 weeks, 101 (42); eosinophil ≥ 300 cells/μL placebo, 103 (42); eosinophil < 300 cells/μL benralizumab 30 mg every 4 weeks, 45 (39); eosinophil < 300 cells/μL benralizumab 30 mg every 8 weeks, 38 (30); eosinophil < 300 cells/μL placebo, 46 (38).
Baseline mean (SD) FEV1 % predicted: eosinophil ≥ 300 cells/μL benralizumab 30 mg every 4 weeks, 59 (13.7); eosinophil ≥ 300 cells/μL benralizumab 30 mg every 8 weeks, 57 (14.2); eosinophil ≥ 300 cells/μL placebo, 58 (13.9); eosinophil < 300 cells/μL benralizumab 30 mg every 4 weeks, 57 (16.2); eosinophil < 300 cells/μL benralizumab 30 mg every 8 weeks, 57 (15.2); eosinophil < 300 cells/μL placebo, 56 (16.3)
Allocation: eosinophil ≥ 300 cells/μL benralizumab 30 mg every 4 weeks, 241; eosinophil ≥ 300 cells/μL benralizumab 30 mg every 8 weeks, 239; eosinophil ≥ 300 cells/μL placebo, 248; eosinophil < 300 cells/μL benralizumab 30 mg every 4 weeks, 116; eosinophil < 300 cells/μL benralizumab 30 mg every 8 weeks, 125; eosinophil < 300 cells/μL placebo, 122
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Interventions |
56 weeks (final follow‐up at 60 weeks). Benralizumab SC 30 mg every 4 weeks for 56 weeks or every 4 weeks for 3 doses then 8 weeks thereafter for 56 weeks |
Outcomes |
Primary outcomes
Annual asthma exacerbations
Secondary outcomes
Pre‐bronchodilator FEV1
Total asthma symptom score
Time to first asthma exacerbation
Annual rate of asthma exacerbations associated with an ED visit, urgent care visit, or admission to hospital
Post‐bronchodilator FEV1
ACQ‐6 score
AQLQ(S)+12 score
EQ‐5D‐5L visual analogue scale (to rate current health status)
Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire
Use of healthcare resources
Participant and clinician assessment of response to treatment
Pharmacokinetic parameter s and anti‐drug antibodies
Safety and tolerability of intervention
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Notes |
Funding: AstraZeneca and Kyowa Hakko Kirin. 303 clinical research centres in 11 countries |
Risk of bias |
Bias |
Authors' judgement |
Support for judgement |
Random sequence generation (selection bias) |
Low risk |
Participants were assigned to treatment groups using an interactive web‐based voice‐response system. Randomisation was stratified by ICS dosage at enrolment (high or medium), geographic region, age group (adult or adolescent), and peripheral blood eosinophil count at enrolment (< 300 cells/μL or ≥ 300 cells/μL) |
Allocation concealment (selection bias) |
Low risk |
The study investigator assigned randomisation codes sequentially in each stratum as participants became eligible for randomisation, until each stratum was full |
Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
To preserve blinding, participants and study centre staff were masked to treatment allocation, placebo solution was visually matched with benralizumab solution, and both placebo and benralizumab were provided in accessorised (needle guards and finger phalanges), prefilled syringes. |
Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
As above |
Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
The withdrawal rates were relatively low: placebo 11.1% (49/440); benralizumab 30 mg every 4 weeks 9.6% (41/425); benralizumab 30 mg every eight weeks 13.4% (59/441) |
Selective reporting (reporting bias) |
Low risk |
Results for all listed primary and secondary outcomes were reported. |