Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

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

3}, Ivan Solà², Pablo Alonso-Coello^{2

4}, Cezmi Akdis⁵, Mubeccel Akdis⁵, Giorgio W Canonica⁶, Thomas Casale⁷, Tomas Chivato⁸, Jonathan Corren⁹, Stefano Del Giacco¹⁰, Thomas Eiwegger^{11

12

13}, Davide Firinu¹⁰, James E Gern¹⁴, Eckard Hamelmann¹⁵, Nicola Hanania¹⁶, Mika Mäkelä¹⁷, Irene Hernández Martín¹⁸, Parameswaran Nair^{19

20}, Liam O'Mahony²¹, Nikolaos G Papadopoulos^{22

23}, Alberto Papi²⁴, Hae-Sim Park²⁵, Luis Pérez de Llano²⁶, Santiago Quirce²⁷, Joaquin Sastre²⁸, Mohamed Shamji^{29

30}, Jurgen Schwarze³¹, Carlos Canelo-Aybar^{2

5}, Oscar Palomares³², Marek Jutel^{33

34}

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

PMID: 32064642
DOI: 10.1111/all.14235

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Ioana Agache et al. Allergy. 2020 May.

. 2020 May;75(5):1043-1057.

doi: 10.1111/all.14235.

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

PMID: 32064642
DOI: 10.1111/all.14235

Abstract

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 - 0.81); dupilumab IRR 0.58 (95%CI 0.47 - 0.73); and omalizumab IRR 0.56 (95%CI 0.42 - 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].

Keywords: benralizumab; dupilumab; exacerbations; omalizumab; severe allergic asthma.

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References

REFERENCES

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Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Affiliations

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical