Table 1

Key study characteristics and methods

Characteristic	METREX		METREO
Population	All patients receiving ≥1 dose of mepolizumab or placebo	Patients with blood eosinophils ≥150 cells·μL⁻¹ at screening or ≥300 cells·μL⁻¹	Patients with blood eosinophils ≥150 cells·μL⁻¹ at screening or ≥300 cells·μL⁻¹
Intervention 1	Mepolizumab 100 mg s.c. (n=417)	Mepolizumab 100 mg s.c. (n=233)	Mepolizumab 100 mg s.c. (n=223)
Intervention 2			Mepolizumab 300 mg s.c. (n=225)
Control	Placebo (0.9% saline) s.c. (n=419)	Placebo (0.9% saline) s.c. (n=229)	Placebo (0.9% saline) s.c. (n=226)
Key inclusion criteria	COPD diagnosis: history of COPD for ≥1 year in accordance with the definition provided by the American Thoracic Society/European Respiratory Society [17]
	FEV₁ to FVC ratio <0.70 before and after bronchodilator use and a post-bronchodilator FEV₁ >20% and ≤80% of the predicted value
	≥2 moderate COPD exacerbations (use of systemic corticosteroids and/or treatment with antibiotics) or ≥1 severe COPD exacerbation (required hospitalisation)
	Triple inhaled therapy for at least 12 months prior to screening including 3 months of an ICS at dose ≥500 μg·day⁻¹ fluticasone propionate dose equivalent, plus LABA and LAMA; or must be taking for 12 months prior to screening (but not in 3 months immediately prior) ICS plus LABA or LAMA and a phosphodiesterase-4 inhibitor, methylxanthine, or a combination of short-acting β₂-agonist and short-acting muscarinic antagonist
	≥40 years of age at screening
	Confirmed COPD with no restrictions on smoking status (smoker, nonsmoker, never-smoker)
Key exclusion criteria	Current diagnosis of asthma
	Previous history of asthma in never-smokers
	Other respiratory disorders, including α₁-antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
	Pneumonia, exacerbation, lower respiratory tract infection within 4 weeks prior to screening
	Other conditions causing elevated eosinophils or parasitic infection
Randomisation	Computer-generated, permuted block
Analysis	Intention-to-treat
Primary end-point	Yearly rate of moderate to severe exacerbations
Secondary end-points	Time to first exacerbation
	Emergency department visits
	Hospitalisation
	Average yearly change in St George's Respiratory Questionnaire score
	Average yearly change in COPD Assessment Test score
Pre-specified meta-analysis	Blood eosinophil stratification based on the following thresholds: <150 and a history of ≥300 cells·μL⁻¹ in the previous year; ≥150 to <300 cells·μL⁻¹; ≥300 to <500 cells·μL⁻¹; and ≥500 cells·μL⁻¹
Post hoc meta-analysis	Blood eosinophils <150 cells·μL⁻¹, blood eosinophils ≥300 cells·μL⁻¹
Post hoc meta-analysis	Effect of mepolizumab compared to placebo on moderate/severe exacerbations treated with glucocorticoids (alone or in addition to antibiotics), or those treated with antibiotics alone

FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; ICS: inhaled corticosteroid; LABA: long-acting β₂-agonist; LAMA: long-acting muscarinic-receptor antagonist.