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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 |
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| Authors: | Ioana Agache Yang Song Claudio Rocha Jessica Beltran Margarita Posso Corinna Steiner Pablo Alonso-Coello Cezmi Akdis Mubeccel Akdis Giorgio Walter Canonica Thomas Casale Tomas Chivato Jonathan Corren Stefano del Giacco Thomas Eiwegger Davide Firinu James E Gern Eckard Hamelmann Nicola Hanania Mika Mäkelä Irene Hernández Martín Parameswaran Nair Liam O'Mahony Nikolaos G Papadopoulos Alberto Papi Hae-Sim Park Luis Pérez de Llano Santiago Quirce Joaquin Sastre Mohamed Shamji Jurgen Schwarze Carlos Canelo-Aybar Oscar Palomares Marek Jutel |
| Institution: | 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. Iberoamerican Cochrane Centre – Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain;4. Iberoamerican Cochrane Centre – Department of Clinical Epidemiology and Public Health, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain 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, Monserrato, Italy;11. Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada;12. Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA;13. Klinik für Kinder- und Jugendmedizin Kinderzentrum Bethel, Bielefeld, Germany;14. Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA;15. Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;16. Department of Allergy, Hospital Universitario La Paz, Madrid, Spain;17. Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada;18. Departments of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland;19. Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK;20. Department of Medical Sciences, Research Center on Asthma and COPD, University of Ferrara, Ferrara, Italy;21. Department of Allergy and Clinical Immunology, Ajou University, Suwon, South Korea;22. Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain;23. Department of Allergy, La Paz University Hospital, IdiPAZ, CIBER of Respiratory Diseases (CIBERES), Universidad Autónoma de Madrid, Madrid, Spain;24. Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain;25. Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, National Heart and Lung Institute, London, UK;26. Centre for Inflammation Research, Child Life and Health, The University of Edinburgh, Edinburgh, UK;27. Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Madrid, Spain;28. Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland All-MED Medical Research Institute, Wroclaw, Poland |
| 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 |