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

Agache I; Beltran J; Akdis C; Akdis M; Canelo-Aybar C; Canonica GW; Casale T; Chivato T; Corren J; Del Giacco S; Eiwegger T; Firinu D; Gern JE; Hamelmann E; Hanania N; Mäkelä M; Hernández-Martín I; Nair P; O'Mahony L; Papadopoulos NG; Papi A; Park HS; Pérez de Llano L; Posso M; Rocha C; Quirce S; Sastre J; Shamji M; Song Y; Steiner C; Schwarze J; Alonso-Coello P; Palomares O; Jutel M

doi:10.1111/all.14221

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

Agache I Faculty of Medicine, Transylvania University, Brasov, Romania.
Beltran J Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Akdis C Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Akdis M Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Canelo-Aybar C Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Canonica GW Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.
Casale T Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Chivato T School of Medicine, University CEU San Pablo, Madrid, Spain.
Corren J David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Del Giacco S Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Eiwegger T Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
Firinu D Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Gern JE Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Hamelmann E Klinik für Kinder- und Jugendmedizin Kinderzentrum Bethel, Bielefeld, Germany.
Hanania N Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
Mäkelä M Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Hernández-Martín I Department of Allergy, Hospital Universitario La Paz, Madrid, Spain.
Nair P Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
O'Mahony L Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
Papadopoulos NG Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK.
Papi A Research Center on Asthma and COPD, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Park HS Department of Allergy and Clinical Immunology, Ajou University, Suwon, Korea.
Pérez de Llano L Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain.
Posso M Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Rocha C Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Quirce S Department of Allergy, La Paz University Hospital, IdiPAZ, CIBER of Respiratory Diseases (CIBERES), Universidad Autónoma de Madrid, Madrid, Spain.
Sastre J Universidad Autónoma de Madrid Facultad de Medicina, Madrid, Spain.
Shamji M Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair, Development, National Heart and Lung Institute, London, UK.
Song Y Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Steiner C Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Schwarze J Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UK.
Alonso-Coello P Iberoamerican Cochrane Centre, Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Palomares O Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Madrid, Spain.
Jutel M Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

2020-02-09

Published in:

Allergy. - 2020

English Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic 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 for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.

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