Benralizumab for the Prevention of COPD Exacerbations

GALATHEA Study Investigators, Uffe Bødtger (Member of author group), TERRANOVA Study Investigators

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.

METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.

RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.

CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Original languageEnglish
JournalThe New England Journal of Medicine
Volume381
Issue number11
Pages (from-to)1023-1034
ISSN0028-4793
DOIs
Publication statusPublished - 12. Sep 2019

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Chronic Obstructive Pulmonary Disease
Placebos
Confidence Intervals
Eosinophils
Interleukin-5 Receptors
Safety
Guidelines

Bibliographical note

Copyright © 2019 Massachusetts Medical Society.

Keywords

  • Aged
  • Anti-Asthmatic Agents/administration & dosage
  • Antibodies, Monoclonal, Humanized/administration & dosage
  • Double-Blind Method
  • Eosinophils/metabolism
  • Female
  • Humans
  • Injections, Subcutaneous
  • Leukocyte Count
  • Male
  • Middle Aged
  • Patient Acuity
  • Pulmonary Disease, Chronic Obstructive/drug therapy
  • Receptors, Interleukin-5/antagonists & inhibitors

Cite this

GALATHEA Study Investigators, Bødtger, U., & TERRANOVA Study Investigators (2019). Benralizumab for the Prevention of COPD Exacerbations. The New England Journal of Medicine, 381(11), 1023-1034. https://doi.org/10.1056/NEJMoa1905248
GALATHEA Study Investigators ; Bødtger, Uffe ; TERRANOVA Study Investigators. / Benralizumab for the Prevention of COPD Exacerbations. In: The New England Journal of Medicine. 2019 ; Vol. 381, No. 11. pp. 1023-1034.
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title = "Benralizumab for the Prevention of COPD Exacerbations",
abstract = "BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95{\%} confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95{\%} CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95{\%} CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95{\%} CI, 0.87 to 1.13), 1.21 per year (95{\%} CI, 1.08 to 1.37), 1.09 per year (95{\%} CI, 0.96 to 1.23), and 1.17 per year (95{\%} CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).",
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author = "Criner, {Gerard J} and Celli, {Bartolome R} and Brightling, {Christopher E} and Alvar Agusti and Alberto Papi and Dave Singh and Sin, {Don D} and Vogelmeier, {Claus F} and Sciurba, {Frank C} and Mona Bafadhel and Vibeke Backer and Motokazu Kato and Alejandra Ram{\'i}rez-Venegas and Yu-Feng Wei and Leif Bjermer and Shih, {Vivian H} and Maria Jison and Sean O'Quinn and Natalya Makulova and Paul Newbold and Mitchell Goldman and Martin, {Ubaldo J} and {GALATHEA Study Investigators} and Uffe B{\o}dtger and {TERRANOVA Study Investigators}",
note = "Copyright {\circledC} 2019 Massachusetts Medical Society.",
year = "2019",
month = "9",
day = "12",
doi = "10.1056/NEJMoa1905248",
language = "English",
volume = "381",
pages = "1023--1034",
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GALATHEA Study Investigators, Bødtger, U & TERRANOVA Study Investigators 2019, 'Benralizumab for the Prevention of COPD Exacerbations', The New England Journal of Medicine, vol. 381, no. 11, pp. 1023-1034. https://doi.org/10.1056/NEJMoa1905248

Benralizumab for the Prevention of COPD Exacerbations. / GALATHEA Study Investigators ; Bødtger, Uffe (Member of author group); TERRANOVA Study Investigators.

In: The New England Journal of Medicine, Vol. 381, No. 11, 12.09.2019, p. 1023-1034.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Benralizumab for the Prevention of COPD Exacerbations

AU - Criner, Gerard J

AU - Celli, Bartolome R

AU - Brightling, Christopher E

AU - Agusti, Alvar

AU - Papi, Alberto

AU - Singh, Dave

AU - Sin, Don D

AU - Vogelmeier, Claus F

AU - Sciurba, Frank C

AU - Bafadhel, Mona

AU - Backer, Vibeke

AU - Kato, Motokazu

AU - Ramírez-Venegas, Alejandra

AU - Wei, Yu-Feng

AU - Bjermer, Leif

AU - Shih, Vivian H

AU - Jison, Maria

AU - O'Quinn, Sean

AU - Makulova, Natalya

AU - Newbold, Paul

AU - Goldman, Mitchell

AU - Martin, Ubaldo J

AU - GALATHEA Study Investigators

AU - TERRANOVA Study Investigators

A2 - Bødtger, Uffe

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2019/9/12

Y1 - 2019/9/12

N2 - BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

AB - BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

KW - Aged

KW - Anti-Asthmatic Agents/administration & dosage

KW - Antibodies, Monoclonal, Humanized/administration & dosage

KW - Double-Blind Method

KW - Eosinophils/metabolism

KW - Female

KW - Humans

KW - Injections, Subcutaneous

KW - Leukocyte Count

KW - Male

KW - Middle Aged

KW - Patient Acuity

KW - Pulmonary Disease, Chronic Obstructive/drug therapy

KW - Receptors, Interleukin-5/antagonists & inhibitors

U2 - 10.1056/NEJMoa1905248

DO - 10.1056/NEJMoa1905248

M3 - Journal article

C2 - 31112385

VL - 381

SP - 1023

EP - 1034

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 11

ER -

GALATHEA Study Investigators, Bødtger U, TERRANOVA Study Investigators. Benralizumab for the Prevention of COPD Exacerbations. The New England Journal of Medicine. 2019 Sep 12;381(11):1023-1034. https://doi.org/10.1056/NEJMoa1905248