Benralizumab for the Prevention of COPD Exacerbations
Copyright © 2019 Massachusetts Medical Society..
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.).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:381 |
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| Enthalten in: |
The New England journal of medicine - 381(2019), 11 vom: 12. Sept., Seite 1023-1034 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Criner, Gerard J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.09.2019 Date Revised 06.12.2022 published: Print-Electronic ClinicalTrials.gov: NCT02138916, NCT02155660 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa1905248 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM29730772X |
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| 245 | 1 | 0 | |a Benralizumab for the Prevention of COPD Exacerbations |
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| 500 | |a Date Completed 20.09.2019 | ||
| 500 | |a Date Revised 06.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02138916, NCT02155660 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Massachusetts Medical Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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.) | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Asthmatic Agents |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-5 |2 NLM | |
| 650 | 7 | |a benralizumab |2 NLM | |
| 650 | 7 | |a 71492GE1FX |2 NLM | |
| 700 | 1 | |a Celli, Bartolome R |e verfasserin |4 aut | |
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| 700 | 1 | |a Sin, Don D |e verfasserin |4 aut | |
| 700 | 1 | |a Vogelmeier, Claus F |e verfasserin |4 aut | |
| 700 | 1 | |a Sciurba, Frank C |e verfasserin |4 aut | |
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| 700 | 1 | |a Ramírez-Venegas, Alejandra |e verfasserin |4 aut | |
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| 700 | 1 | |a Bjermer, Leif |e verfasserin |4 aut | |
| 700 | 1 | |a Shih, Vivian H |e verfasserin |4 aut | |
| 700 | 1 | |a Jison, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a O'Quinn, Sean |e verfasserin |4 aut | |
| 700 | 1 | |a Makulova, Natalya |e verfasserin |4 aut | |
| 700 | 1 | |a Newbold, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Goldman, Mitchell |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Ubaldo J |e verfasserin |4 aut | |
| 700 | 0 | |a GALATHEA Study Investigators |e verfasserin |4 aut | |
| 700 | 0 | |a TERRANOVA Study Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Burghuber, Otto |e investigator |4 oth | |
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