Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts
Copyright © 2023 Massachusetts Medical Society..
BACKGROUND: In some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammation may increase exacerbation risk and may be indicated by elevated blood eosinophil counts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation.
METHODS: In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of at least 300 per microliter and an elevated exacerbation risk despite the use of standard triple therapy to receive dupilumab (300 mg) or placebo subcutaneously once every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations of COPD. Key secondary and other end points that were corrected for multiplicity were the change in the prebronchodilator forced expiratory volume in 1 second (FEV1) and in the scores on the St. George's Respiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating a better quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS-COPD; range, 0 to 40, with lower scores indicating less severe symptoms).
RESULTS: A total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the SGRQ score had improved by an LS mean of -9.7 (95% CI, -11.3 to -8.1) with dupilumab and -6.4 (95% CI, -8.0 to -4.8) with placebo (LS mean difference, -3.4; 95% CI, -5.5 to -1.3; P = 0.002). The E-RS-COPD score at week 52 had improved by an LS mean of -2.7 (95% CI, -3.2 to -2.2) with dupilumab and -1.6 (95% CI, -2.1 to -1.1) with placebo (LS mean difference, -1.1; 95% CI, -1.8 to -0.4; P = 0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups.
CONCLUSIONS: Among patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts, those who received dupilumab had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; BOREAS ClinicalTrials.gov number, NCT03930732.).
| Errataetall: |
CommentIn: Ann Intern Med. 2023 Sep;176(9):JC102. - PMID 37665985 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:389 |
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| Enthalten in: |
The New England journal of medicine - 389(2023), 3 vom: 20. Juli, Seite 205-214 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bhatt, Surya P [VerfasserIn] |
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| Links: |
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| Themen: |
420K487FSG |
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| Anmerkungen: |
Date Completed 24.07.2023 Date Revised 25.09.2023 published: Print-Electronic ClinicalTrials.gov: NCT03930732 CommentIn: Ann Intern Med. 2023 Sep;176(9):JC102. - PMID 37665985 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2303951 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357745442 |
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| 245 | 1 | 0 | |a Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts |
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| 500 | |a Date Revised 25.09.2023 | ||
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| 500 | |a ClinicalTrials.gov: NCT03930732 | ||
| 500 | |a CommentIn: Ann Intern Med. 2023 Sep;176(9):JC102. - PMID 37665985 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: In some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammation may increase exacerbation risk and may be indicated by elevated blood eosinophil counts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation | ||
| 520 | |a METHODS: In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of at least 300 per microliter and an elevated exacerbation risk despite the use of standard triple therapy to receive dupilumab (300 mg) or placebo subcutaneously once every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations of COPD. Key secondary and other end points that were corrected for multiplicity were the change in the prebronchodilator forced expiratory volume in 1 second (FEV1) and in the scores on the St. George's Respiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating a better quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS-COPD; range, 0 to 40, with lower scores indicating less severe symptoms) | ||
| 520 | |a RESULTS: A total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the SGRQ score had improved by an LS mean of -9.7 (95% CI, -11.3 to -8.1) with dupilumab and -6.4 (95% CI, -8.0 to -4.8) with placebo (LS mean difference, -3.4; 95% CI, -5.5 to -1.3; P = 0.002). The E-RS-COPD score at week 52 had improved by an LS mean of -2.7 (95% CI, -3.2 to -2.2) with dupilumab and -1.6 (95% CI, -2.1 to -1.1) with placebo (LS mean difference, -1.1; 95% CI, -1.8 to -0.4; P = 0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups | ||
| 520 | |a CONCLUSIONS: Among patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts, those who received dupilumab had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; BOREAS ClinicalTrials.gov number, NCT03930732.) | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a dupilumab |2 NLM | |
| 650 | 7 | |a 420K487FSG |2 NLM | |
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| 700 | 1 | |a Akinlade, Bolanle |e verfasserin |4 aut | |
| 700 | 1 | |a Maloney, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Bauer, Deborah |e verfasserin |4 aut | |
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| 700 | 1 | |a Robinson, Lacey B |e verfasserin |4 aut | |
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| 700 | 0 | |a BOREAS Investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a Piza, Hernan Daniel |e investigator |4 oth | |
| 700 | 1 | |a Aramayo, Norma |e investigator |4 oth | |
| 700 | 1 | |a De Stefano, Gaston |e investigator |4 oth | |
| 700 | 1 | |a Del Olmo, Ricardo |e investigator |4 oth | |
| 700 | 1 | |a Carminio, Cristian |e investigator |4 oth | |
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