Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
Treatment of uncontrolled asthma with dupilumab, an anti–interleukin-4 and anti–interleukin-13 receptor monoclonal antibody, in addition to usual therapy, led to a rate of severe exacerbations that was approximately 50% lower than the rate with placebo.
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| Vydáno v: | The New England journal of medicine Ročník 378; číslo 26; s. 2486 - 2496 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
Massachusetts Medical Society
28.06.2018
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| ISSN: | 0028-4793, 1533-4406, 1533-4406 |
| On-line přístup: | Získat plný text |
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| Abstract | Treatment of uncontrolled asthma with dupilumab, an anti–interleukin-4 and anti–interleukin-13 receptor monoclonal antibody, in addition to usual therapy, led to a rate of severe exacerbations that was approximately 50% lower than the rate with placebo. |
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| AbstractList | Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV
) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV
in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed.
The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV
had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo.
In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .). Treatment of uncontrolled asthma with dupilumab, an anti–interleukin-4 and anti–interleukin-13 receptor monoclonal antibody, in addition to usual therapy, led to a rate of severe exacerbations that was approximately 50% lower than the rate with placebo. Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854.) Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.BACKGROUNDDupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed.METHODSWe randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed.The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo.RESULTSThe annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo.In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).CONCLUSIONSIn this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .). |
| Author | Corren, Jonathan Stahl, Neil Chao, Jingdong Castro, Mario Khan, Asif Maspero, Jorge Busse, William W Katelaris, Constance Sher, Lawrence Ruddy, Marcella Amin, Nikhil Hamilton, Jennifer D FitzGerald, J. Mark Swanson, Brian N Wenzel, Sally Pirozzi, Gianluca Akinlade, Bolanle Teper, Ariel Zhang, Bingzhi Ford, Linda Martincova, Renata Pavord, Ian D Graham, Neil M.H Yancopoulos, George D Staudinger, Heribert Rabe, Klaus F Tohda, Yuji |
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Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 13 givenname: Bingzhi surname: Zhang fullname: Zhang, Bingzhi organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 14 givenname: Heribert surname: Staudinger fullname: Staudinger, Heribert organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 15 givenname: Gianluca surname: Pirozzi fullname: Pirozzi, Gianluca organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 16 givenname: Nikhil surname: Amin fullname: Amin, Nikhil organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 17 givenname: Marcella surname: Ruddy fullname: Ruddy, Marcella organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 18 givenname: Bolanle surname: Akinlade fullname: Akinlade, Bolanle organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 19 givenname: Asif surname: Khan fullname: Khan, Asif organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 20 givenname: Jingdong surname: Chao fullname: Chao, Jingdong organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 21 givenname: Renata surname: Martincova fullname: Martincova, Renata organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 22 givenname: Neil M.H surname: Graham fullname: Graham, Neil M.H organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 23 givenname: Jennifer D surname: Hamilton fullname: Hamilton, Jennifer D organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 24 givenname: Brian N surname: Swanson fullname: Swanson, Brian N organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 25 givenname: Neil surname: Stahl fullname: Stahl, Neil organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 26 givenname: George D surname: Yancopoulos fullname: Yancopoulos, George D organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) – sequence: 27 givenname: Ariel surname: Teper fullname: Teper, Ariel organization: From the Washington University School of Medicine, St. Louis (M.C.); David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J. Corren), and Peninsula Research Associates, Rolling Hills Estates (L.S.) — both in California; Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom (I.D.P.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.M.); the University of Pittsburgh Asthma Institute, University of Pittsburgh, Pittsburgh (S.W.); LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel — both in Germany (K.F.R.); the Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Asthma and Allergy Center, Bellevue, NE (L.F.); the University of British Columbia, Vancouver, Canada (J.M.F.); Campbelltown Hospital and Western Sydney University, Sydney (C.K.); the Faculty of Medicine, Kindai University, Osakasayama, Japan (Y.T.); Sanofi, Bridgewater, NJ (B.Z., H.S., G.P., B.N.S., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (N.A., M.R., B.A., J. Chao, N.M.H.G., J.D.H., N.S., G.D.Y.); Sanofi, Chilly-Mazarin, France (A.K.); and Sanofi, Prague, Czech Republic (R.M.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29782217$$D View this record in MEDLINE/PubMed |
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| Title | Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma |
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