Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma

Ioana Agache¹, Yang Song², Claudio Rocha², Jessica Beltran², Margarita Posso^{2

3}, Corinna Steiner², Pablo Alonso-Coello^{2

4}, Cezmi Akdis^{5

6}, Mubeccel Akdis^{5

6}, Giorgio Walter Canonica⁷, Thomas Casale⁸, Tomas Chivato⁹, Jonathan Corren¹⁰, Stefano Del Giacco¹¹, Thomas Eiwegger^{12

13

14}, Davide Firinu¹¹, James E Gern¹⁵, Eckard Hamelmann¹⁶, Nicola Hanania¹⁷, Mika Mäkelä¹⁸, Irene Hernández Martín¹⁹, Parameswaran Nair^{20

21}, Liam O'Mahony²², Nikolaos G Papadopoulos^{23

24}, Alberto Papi²⁵, Hae-Sim Park²⁶, Luis Pérez de Llano²⁷, Santiago Quirce²⁸, Joaquin Sastre²⁹, Mohamed Shamji^{30

31}, Jurgen Schwarze³², Carlos Canelo-Aybar^{2

4}, Oscar Palomares³³, Marek Jutel^{34

35}

Affiliations

¹ Faculty of Medicine, Transylvania University, Brasov, Romania.
² Iberoamerican Cochrane Centre - Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
³ Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
⁴ CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁵ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
⁶ Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
⁷ Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.
⁸ Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
⁹ School of Medicine, University CEU San Pablo, Madrid, Spain.
¹⁰ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹¹ Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.
¹² Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
¹³ Department of Immunology, University of Toronto, Toronto, ON, Canada.
¹⁴ Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, Departments of Paediatrics and Immunology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
¹⁶ Klinik für Kinder- und Jugendmedizin Kinderzentrum Bethel, Bielefeld, Germany.
¹⁷ Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
¹⁸ Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁹ Department of Allergy, Hospital Universitario La Paz, Madrid, Spain.
²⁰ Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, ON, Canada.
²² Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
²³ Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²⁴ Allergy Department, 2nd Pediatric Clinic, National Kapodistrian University of Athens, Athens, Greece.
²⁵ Department of Medical Sciences, Research Center on Asthma and COPD, University of Ferrara, Ferrara, Italy.
²⁶ Department of Allergy and Clinical Immunology, Ajou University, Suwon, South Korea.
²⁷ Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain.
²⁸ Department of Allergy, La Paz University Hospital, IdiPAZ, CIBER of Respiratory Diseases (CIBERES), Universidad Autónoma de Madrid, Madrid, Spain.
²⁹ Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
³⁰ Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, National Heart and Lung Institute, London, UK.
³¹ Imperial College NIHR Biomedical Research Centre, Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
³² Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UK.
³³ Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Madrid, Spain.
³⁴ Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.
³⁵ ALL-MED" Medical Research Institute, Wroclaw, Poland.

PMID: 32154939
DOI: 10.1111/all.14268

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma

Ioana Agache et al. Allergy. 2020 May.

. 2020 May;75(5):1058-1068.

doi: 10.1111/all.14268. Epub 2020 Apr 1.

Authors

Affiliations

¹ Faculty of Medicine, Transylvania University, Brasov, Romania.
² Iberoamerican Cochrane Centre - Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
³ Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
⁴ CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁵ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
⁶ Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
⁷ Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.
⁸ Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
⁹ School of Medicine, University CEU San Pablo, Madrid, Spain.
¹⁰ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹¹ Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.
¹² Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
¹³ Department of Immunology, University of Toronto, Toronto, ON, Canada.
¹⁴ Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, Departments of Paediatrics and Immunology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
¹⁶ Klinik für Kinder- und Jugendmedizin Kinderzentrum Bethel, Bielefeld, Germany.
¹⁷ Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
¹⁸ Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁹ Department of Allergy, Hospital Universitario La Paz, Madrid, Spain.
²⁰ Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, ON, Canada.
²² Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
²³ Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²⁴ Allergy Department, 2nd Pediatric Clinic, National Kapodistrian University of Athens, Athens, Greece.
²⁵ Department of Medical Sciences, Research Center on Asthma and COPD, University of Ferrara, Ferrara, Italy.
²⁶ Department of Allergy and Clinical Immunology, Ajou University, Suwon, South Korea.
²⁷ Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain.
²⁸ Department of Allergy, La Paz University Hospital, IdiPAZ, CIBER of Respiratory Diseases (CIBERES), Universidad Autónoma de Madrid, Madrid, Spain.
²⁹ Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
³⁰ Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, National Heart and Lung Institute, London, UK.
³¹ Imperial College NIHR Biomedical Research Centre, Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
³² Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UK.
³³ Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Madrid, Spain.
³⁴ Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.
³⁵ ALL-MED" Medical Research Institute, Wroclaw, Poland.

PMID: 32154939
DOI: 10.1111/all.14268

Abstract

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV₁ increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.

Keywords: cost-effectiveness; dupilumab; exacerbations; oral corticosteroids; severe asthma.

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References

REFERENCES

1. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-J.... Accessed January 22, 2020.
1. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588.
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Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma

Affiliations

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical