Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype

MATINEE Study Investigators

doi:10.1056/NEJMoa2413181

Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype

MATINEE Study Investigators

Peter Gorer Department of Immunobiology

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

BACKGROUND: Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).

METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both.

RESULTS: Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups.

CONCLUSIONS: Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype. (Funded by GSK; MATINEE ClinicalTrials.gov number, NCT04133909.).

Original language	English
Pages (from-to)	1710-1720
Number of pages	11
Journal	New England Journal of Medicine
Volume	392
Issue number	17
DOIs	https://doi.org/10.1056/NEJMoa2413181
Publication status	Published - 1 May 2025

Keywords

Aged
Female
Humans
Male
Middle Aged
Administration, Inhalation
Antibodies, Monoclonal, Humanized/administration & dosage
Disease Progression
Double-Blind Method
Drug Therapy, Combination
Eosinophilia/blood
Eosinophils/drug effects
Injections, Subcutaneous
Interleukin-5/antagonists & inhibitors
Phenotype
Pulmonary Disease, Chronic Obstructive/complications
Quality of Life
Severity of Illness Index
Treatment Outcome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/NEJMoa2413181

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@article{0ff6c1e50bd94ced8c7ef36be6eab660,

title = "Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype",

abstract = "BACKGROUND: Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both.RESULTS: Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups.CONCLUSIONS: Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype. (Funded by GSK; MATINEE ClinicalTrials.gov number, NCT04133909.).",

keywords = "Aged, Female, Humans, Male, Middle Aged, Administration, Inhalation, Antibodies, Monoclonal, Humanized/administration & dosage, Disease Progression, Double-Blind Method, Drug Therapy, Combination, Eosinophilia/blood, Eosinophils/drug effects, Injections, Subcutaneous, Interleukin-5/antagonists & inhibitors, Phenotype, Pulmonary Disease, Chronic Obstructive/complications, Quality of Life, Severity of Illness Index, Treatment Outcome",

author = "{MATINEE Study Investigators} and Sciurba, {Frank C} and Criner, {Gerard J} and Christenson, {Stephanie A} and Martinez, {Fernando J} and Alberto Papi and Nicolas Roche and Jean Bourbeau and Stephanie Korn and Mona Bafadhel and Han, {MeiLan K} and Stefanie Kolterer and Karen Miller and Dalal Mouneimne and Joanne Fletcher and Bhabita Mayer and Jeff Min and Pavord, {Ian D}",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 Massachusetts Medical Society.",

year = "2025",

month = may,

day = "1",

doi = "10.1056/NEJMoa2413181",

language = "English",

volume = "392",

pages = "1710--1720",

journal = "New England Journal of Medicine",

issn = "1533-4406",

publisher = "Massachussetts Medical Society",

number = "17",

}

TY - JOUR

T1 - Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype

AU - MATINEE Study Investigators

AU - Sciurba, Frank C

AU - Criner, Gerard J

AU - Christenson, Stephanie A

AU - Martinez, Fernando J

AU - Papi, Alberto

AU - Roche, Nicolas

AU - Bourbeau, Jean

AU - Korn, Stephanie

AU - Bafadhel, Mona

AU - Han, MeiLan K

AU - Kolterer, Stefanie

AU - Miller, Karen

AU - Mouneimne, Dalal

AU - Fletcher, Joanne

AU - Mayer, Bhabita

AU - Min, Jeff

AU - Pavord, Ian D

PY - 2025/5/1

Y1 - 2025/5/1

N2 - BACKGROUND: Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both.RESULTS: Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups.CONCLUSIONS: Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype. (Funded by GSK; MATINEE ClinicalTrials.gov number, NCT04133909.).

AB - BACKGROUND: Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both.RESULTS: Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups.CONCLUSIONS: Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype. (Funded by GSK; MATINEE ClinicalTrials.gov number, NCT04133909.).

KW - Aged

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Administration, Inhalation

KW - Antibodies, Monoclonal, Humanized/administration & dosage

KW - Disease Progression

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Eosinophilia/blood

KW - Eosinophils/drug effects

KW - Injections, Subcutaneous

KW - Interleukin-5/antagonists & inhibitors

KW - Phenotype

KW - Pulmonary Disease, Chronic Obstructive/complications

KW - Quality of Life

KW - Severity of Illness Index

KW - Treatment Outcome

UR - http://www.scopus.com/inward/record.url?scp=105004481589&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2413181

DO - 10.1056/NEJMoa2413181

M3 - Article

C2 - 40305712

SN - 1533-4406

VL - 392

SP - 1710

EP - 1720

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 17

ER -

Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype

Abstract

Keywords

UN SDGs

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