Ortega 2014

Methods	Randomised, double‐blind, double‐dummy, phase 3 study
Participants	576 participants with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to 1 of 3 study groups Main inclusion/exclusion criteria: blood eosinophils ≥ 150 cells/μL at screening or ≥ 300 cells/μL in previous 12 months ≥ 2 exacerbations in previous 12 months FEV1 < 80% maintenance treatment with high‐dose ICS for ≥ 12 months; plus additional controller for ≥ 3 months; ± maintenance OCS Age mean (range) years: mepolizumab 75 mg 50 (13‐82); mepolizumab 100 mg 51 (12‐81); placebo, 49 (12‐76) Males (43%): mepolizumab 75 mg, 106 (55); mepolizumab 100 mg, 116 (60); placebo, 107 (56) Baseline mean (SD) FEV1 % predicted: mepolizumab 75 mg, 61.4 ± 18.3; mepolizumab 100 mg, 59.3 ± 17.5; placebo, 62.4 ± 18.1 Allocation: mepolizumab 75 mg, 191; mepolizumab 100 mg, 194; placebo, 191
Interventions	Mepolizumab in a 75 mg intravenous dose versus mepolizumab in a 100 mg subcutaneous dose versus placebo every 4 weeks for 32 weeks
Outcomes	Primary outcomes Number of clinically significant exacerbations of asthma per year Secondary outcomes: Number of clinically significant exacerbations requiring hospitalisation (including intubation and admittance to an intensive care unit ) or ED visits per year Mean change from baseline in clinic pre‐bronchodilator FEV1 at week 32 Mean change from baseline in the SGRQ total score at week 32
Notes	32‐week treatment intervention, with 1‐6 weeks run‐in and 8‐week follow‐up. Conducted in Baltimore, Middlesex, Ghent, Vancouver, Parma, Marseille and Paris Funding: GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centralised computer‐generated permuted block schedule
Allocation concealment (selection bias)	Low risk	Treatment allocations will be concealed via the RandAll system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Mepolizumab and placebo were identical in appearance and were administered by a staff member who was unaware of the study group assignments.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The study drugs were prepared by staff members who were aware of the study group assignments but were not involved in study assessments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	6% (placebo), 8% (IV), 5% ( SC) did not complete the study
Selective reporting (reporting bias)	Low risk	All outcome measures reported