. 2022 Jul 12;2022(7):CD010834. doi: 10.1002/14651858.CD010834.pub4

1. Comparisons of study characteristics.

Study  (number of participants)	Design, follow‐up (weeks)	Baseline asthma severity	Baseline treatment	Intervention (route)	Primary and secondary outcomes
Bernstein 2020 (468)	RCT, double‐blind, placebo‐controlled, parallel‐group (52)	ACQ‐6 score ≥ 1.5; ≥ 2 exacerbations in the last year requiring systemic corticosteroids; blood eosinophils ≥ 300 cells/μL; and FEV₁ bronchodilator reversibility of < 12%	Medium‐dose ICS for ≥ 3 months; + additional controller for ≥ 3 months; ± maintenance OCS	Reslizumab 110 mg (SC) or placebo every 4 weeks for 52 weeks (last dose at 48 weeks)	Clinical asthma exacerbations during 52‐week treatment period Change from baseline pre‐bronchodilator FEV₁ Change from baseline in ACQ‐6 at week 52 Change from baseline in AQLQ+12 at week 52 Change from baseline in SGRQ at week 32
Bjermer 2016 (315)	RCT, double‐blind, placebo‐controlled, parallel‐group, fixed‐dosage, multicentre phase 3 (16)	Blood eosinophils ≥ 400 cells/μL during 2‐4‐week screening period; and ACQ‐7 score ≥ 1.5	Medium‐dose ICS; maintenance OCS not allowed	Reslizumab 0.3 mg/kg or 3 mg/kg (IV) or placebo every 4 weeks for 4 doses	Pre‐bronchodilator FEV₁, FVC, FEF_25-75 ACQ, ACQ‐6, ACQ‐5 ASUI AQLQ Rescue inhaler use Blood eosinophil levels
Bleecker 2016 (1204)	RCT double‐blind, parallel‐group, placebo‐controlled multicentre (52)	≥ 2 exacerbations in the previous 12 months; and ACQ‐6 score ≥ 1.5 at enrolment; and FEV₁ < 80% (if 12‐17 years old, < 90%)	Adults (> 18 years) high‐dose (≥ 500 μg/d FP or equivalent) ICS/LABA for ≥ 12 months Children (12‐17 years) at least medium‐dose (≥ 250 μg/day FP or equivalent) ICS/LABA	Benralizumab 30 mg (SC) or placebo either every 4 weeks or every 4 weeks for the first 3 doses then every 8 weeks or placebo for 48 weeks	Annual exacerbation rate Pre‐bronchodilator FEV₁ Total asthma symptom score Time to first exacerbation Annual rate of exacerbations requiring ED visit or hospital admission Post‐bronchodilator FEV₁ ACQ‐6 AQLQ(S)+12 score
Castro 2015a (489) and Castro 2015b (464)	2 duplicate RCTs, double‐blind, placebo‐controlled, parallel‐group, multicentre, phase 3 (52)	Blood eosinophils ≥ 400 cells/μL during 2‐4‐week screening period; and ACQ‐7 score ≥ 1.5	Medium‐dose ICS (i.e. ≥ 440 μg/day FP or equivalent daily); ± additional controller or maintenance OCS	Reslizumab 3 mg/kg (IV) or matching placebo every 4 weeks for 13 doses (last dose week 48)	Annual frequency of exacerbations Change in FEV₁ from baseline over 16 weeks ACQ‐7 score ASUI score Rescue use of SABA Blood eosinophil count ‐ AQLQ total score at weeks 16, 32 and 52
Castro 2014a (606)	RCT double‐blind, placebo‐controlled, multicentre dose‐ranging (52)	2‐6 exacerbations in the previous 12 months; and ACQ‐6 score ≥ 1.5 at least twice during screening; and morning pre‐bronchodilator FEV₁ 40%‐90%	Medium‐ to high‐dose ICS in combination with LABA for ≥ 12 months	Benralizumab 2 mg, 20 mg or 100 mg (SC) or placebo every 4 weeks for the first 3 doses, then every 8 weeks (total 7 doses)	Annual exacerbation rate Change from baseline in FEV₁ Mean ACQ‐6 score Overall symptom score Mean AQLQ score
Chupp 2017 (551)	RCT, double‐blind, placebo‐controlled (24)	Blood eosinophils ≥ 150 cells/μL at screening or ≥ 300 cells/μL in previous 12 months; and ≥ 2 exacerbations in previous 12 months; and FEV₁ < 80%	High‐dose ICS for ≥ 12 months; + additional controller for ≥ 3 months; ± maintenance OCS	Mepolizumab 100 mg (SC) or placebo every 4 weeks for 24 weeks (last dose at 20 weeks)	SGRQ Mean change from baseline pre‐bronchodilator FEV₁ Proportion of SGRQ total score responders at week 24 Mean change from baseline in ACQ‐5
Corren 2016 (496)	RCT double‐blind, placebo‐controlled, multicentre phase 3 (16)	ACQ‐7 score ≥ 1.5 (no selection based on blood eosinophils)	Medium‐dose ICS; maintenance OCS not allowed	Reslizumab 3 mg/kg (IV) or matching placebo every 4 weeks for 4 doses	Change in FEV₁ from baseline ACQ‐7 score Rescue (SABA) use within previous 3 days FVC Blood eosinophils
FitzGerald 2016 (1306)	RCT, double‐blind, parallel‐group, placebo‐controlled multicentre (56)	≥ 2 exacerbations in the previous 12 months; and ACQ‐6 score ≥ 1.5 at enrolment; and FEV₁ < 80%	Medium‐ (≥ 250 μg/d FP or equivalent) to high‐dose (≥ 500 μg/d FP or equivalent) ICS/LABA for ≥ 12 months; high‐dose ICS/LABA for ≥ 3 months	Benralizumab 30 mg (SC) or placebo either every 4 weeks or every 4 weeks for the first 3 doses then every 8 weeks or placebo	Annual exacerbation rate for participants with blood eosinophils ≥ 300 cells/μL Pre‐bronchodilator FEV₁ Total asthma symptom score Time to first exacerbation Annual rate of exacerbations requiring ED visit or hospital admission Post‐bronchodilator FEV₁ ACQ‐6 AQLQ(S)+12 score
Haldar 2009 (61)	RCT, double‐blind, placebo‐controlled, parallel‐group (50)	≥ 3% sputum eosinophils; and ≥ 2 exacerbations in previous 12 months	High‐dose ICS	Mepolizumab 75 (IV) or matched placebo (150 mL of 0.9% saline) at monthly intervals for 1 year	Severe exacerbations per person Change in AQLQ Post‐bronchodilator FEV₁ Airway hyperresponsiveness Blood/sputum eosinophil counts
Harrison 2020 (656)	RCT, double‐blind, placebo‐controlled, parallel‐group (24)	≥ 2 exacerbations in the last year requiring systemic corticosteroids; FEV₁ < 80%; blood eosinophils ≥ 300 cells/μL or ≥ 150 cells/μL and maintenance OCS or history of nasal polyps or ≥ 2 exacerbations in the last year or FVC < 65% or ≥ 18 years at asthma diagnosis; ACQ‐6 score ≥ 1.5; bronchodilator reversibility ≥ 12% or airway hyperresponsiveness or PEF variability ≥ 10%	Medium‐to‐high‐dose ICS + additional controller for ≥ 3 months; ± maintenance OCS	Benralizumab 30 mg (SC) or placebo every 8 weeks (first 3 doses every 4 weeks) for 24 weeks	Annualised asthma exacerbation rate Change from baseline to week 24 in SGRQ FEV₁ PEF ACQ‐6 PSIA CGI‐C PGI‐C SNOT‐22
Jackson 2022 (290)	RCT triple‐blind, placebo‐controlled	≥ 2 exacerbations in the previous 12 months; peripheral blood eosinophils ≥ 150 cells/µL	For those aged 6‐11 years, treatment with at least medium‐ to high‐dose ICS For those ≥ 12 years of age, treatment with at least medium‐ to high‐dose ICS in combination with LABA	Mepolizumab 40 mg (SC) for 6‐11 year‐olds, 100 mg (SC) for 12‐17 year‐olds every 4 weeks	Asthma exacerbations treated with systemic corticosteroids Time to first exacerbation Lung function Quality of life CASI
Moore 2022 (295)	Randomised, double‐blind, placebo‐controlled, parallel‐group, multicentre study (52)	Patients who had received continuous mepolizumab treatment for ≥ 3 years (initially as part of an RCT, Pavord 2012a, Ortega 2014, or Bel 2014)	Mepolizumab ≥ 6 months + controller medication ≥ 12 weeks	Mepolizumab 100 mg (SC) or placebo every 4 weeks for 52 weeks	Percentage of patients with clinically significant exacerbations (requiring systemic corticosteroids for ≥ 3 days) at 52 weeks Change from baseline in blood eosinophil count Percentage of participants with ≥ 0.5 point increase from baseline in ACQ‐5 Percentage of participants with exacerbations requiring hospitalisation or ED visit
NCT01947946 (13)	RCT double‐blind, parallel‐group, placebo‐controlled multicentre (48)	Uncontrolled asthma taking medium‐dose ICS plus LABA	Medium‐dose ICS (> 250 µg and ≤ 500 µg fluticasone dry powder formulation equivalents total daily dose) and LABA for at least 3 months prior to first visit	Benralizumab 30 mg (SC) or placebo either every 4 weeks or every 4 weeks for the first 3 doses then every 8 weeks or placebo	Asthma exacerbations over 48‐week treatment period
Ortega 2014 (576)	RCT, double‐blind, double‐dummy, phase 3 (32)	Blood eosinophils ≥ 150 cells/μL at screening or ≥ 300 cells/μL in previous 12 months; and ≥ 2 exacerbations in previous 12 months; and FEV₁ < 80%	High‐dose ICS for ≥ 12 months; + additional controller for ≥ 3 months; ± maintenance OCS	Mepolizumab 75 mg (IV) or 100 mg (SC) or placebo every 4 weeks for 32 weeks	Exacerbations per year Mean change from baseline pre‐bronchodilator FEV₁ Mean change from baseline SGRQ total score
Park 2016 (103)	RCT double‐blind, placebo‐controlled, dose‐ranging multicentre (52)	2‐6 exacerbations in the previous 12 months; and ACQ‐6 score ≥ 1.5 at least twice during screening; and morning pre‐bronchodilator FEV₁ 40%‐90%	Medium‐ to high‐dose ICS in combination with LABA for ≥ 12 months	Benralizumab 2 mg, 20 mg or 100 mg (SC) or placebo every 4 weeks for the first 3 doses, then every 8 weeks (total 7 doses)	Annual exacerbation rate Lung function ACQ‐6 FeNO Blood eosinophil counts
Pavord 2012a (621)	Multicentre, double‐blind, placebo‐controlled (52)	≥ 3% sputum eosinophils or blood eosinophil ≥ 300 cells/μL; and ≥ 2 exacerbations in previous 12 months	High‐dose ICS (i.e. ≥ 880 μg/d FP or equivalent daily); + additional controller; ± maintenance OCS	Mepolizumab 75 mg, 250 mg or 750 mg (IV) or placebo every 4 weeks for 13 doses	Time to first clinically significant exacerbation Frequency of exacerbations requiring hospitalisation Time to first exacerbation requiring hospitalisation or ED visit Mean change from baseline pre‐bronchodilator FEV₁ Mean change from baseline post‐bronchodilator FEV₁ Mean change from baseline ACQ
ACQ: Asthma Control Questionnaire; AQLQ: Asthma Quality of Life Questionnaire; ASUI: Asthma Symptom Utility Index; BDP: beclomethasone dipropionate; CASI: Composite Asthma Severity Index; CGI‐C: Clinician Global Impression of Change; ECP: eosinophil cationic protein; ED: emergency department; FEF_25-75: forced expiratory flow at 25% to 75% of FVC; FeNO: exhaled fraction of nitric oxide; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; FP: fluticasone propionate; ICS: inhaled corticosteroid; IV: intravenous; LABA: long‐acting beta₂ agonist; OCS: oral corticosteroid; PC₂₀: histamine provocative concentration causing a 20% drop in FEV₁; PEFR: peak expiratory flow rate; PGI‐C: Patient Global Impression of Change; PSIA: Predominant Symptom and Impairment Assessment; RCT: randomised controlled trial; SABA: short‐acting beta₂‐agonists; SC: subcutaneous; SGRQ: St George's Respiratory Questionnaire; SNOT‐22: Sino‐Nasal Outcome Test‐22