Title
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
Date Issued
01 May 2020
Access level
open access
Resource Type
journal article
Author(s)
Agache I.
Song Y.
Rocha C.
Beltran J.
Posso M.
Steiner C.
Alonso-Coello P.
Akdis C.
Akdis M.
Canonica G.W.
Casale T.
Chivato T.
Corren J.
del Giacco S.
Eiwegger T.
Firinu D.
Gern J.E.
Hamelmann E.
Hanania N.
Mäkelä M.
Martín I.H.
Nair P.
O'Mahony L.
Papadopoulos N.G.
Papi A.
Park H.S.
Pérez de Llano L.
Quirce S.
Sastre J.
Shamji M.
Schwarze J.
Palomares O.
Jutel M.
Instituto de Investigación Biomédica Sant Pau
Publisher(s)
Blackwell Publishing Ltd
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.
Start page
1058
End page
1068
Volume
75
Issue
5
Language
English
OCDE Knowledge area
Sistema respiratorio
Inmunología
Subjects
Scopus EID
2-s2.0-85083105075
PubMed ID
Source
Allergy: European Journal of Allergy and Clinical Immunology
ISSN of the container
01054538
Source funding
Amgen
Sponsor(s)
IA serves as associate editor of Allergy. YS, CR, JB, MP, CS and PA‐C have received funding from EAACI. CA and MA report grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission Horizon 2020 Framework Programme, Cure, Novartis Research Institutes, AstraZeneca and Scibase, and CA is also on the Sanofi/Regeneron advisory board. T Casale reports grants and/or personal fees from Genentech, Novartis, Sanofi‐Regeneron, GSK and Amgen. JC declares grants or personal fees from AZ, Genentech/Roche, Novartis, Optinose, Sanofi, Stallergenes and Teva. S del G reports personal fees from AstraZeneca, GSK and Novartis. TE has received grants or other from DBV, Innovation Fund Denmark, Regeneron and the Allergy and Anaphylaxis Program SickKids, serves as associate editor of Allergy and is on the local advisory board of ALK. JC reports fees from EAACI. JG reports personal fees from Regeneron, Ena Therapeutics and MedImmune/AstraZeneca and stock options from Meissa Vaccines Inc. In addition, JG has a pending patent on Methods of Propagating Rhinovirus C in Previously Unsusceptible Cell Lines, and on Adapted Rhinovirus C. NH reports funding, honoraria or personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Novartis and Sanofi Genzyme, Regeneron, Genentech, Sunovion and Mylan. PN reports grants and/or personal fees from AZ, Novartis, Teva, Sanofi, Roche, Novartis, Merck and Equillium. LOM reports grants from GSK and personal fees from AHL, Nutricia and Nestle. NGP reports personal fees from Novartis, Nutricia, HAL, Menarini/Faes Farma, Sanofi, Mylan/Meda, Biomay, AstraZeneca, GSK, MSD, ASIT Biotech and Boehringer Ingelheim and grants from Gerolymatos International SA and Capricare. AP has received grants, personal fees, nonfinancial support or other from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Teva, Mundipharma, Zambon, Novartis, Menarini, Sanofi/Regeneron, Roche, Fondazione Maugeri, Fondazione Chiesi and Edmond Pharma. LP reports grants, personal fees or nonfinancial support from Novartis, AstraZeneca, GSK, Teva, Boehringer Ingelheim, Chiesi, Sanofi, Menarini, Mundipharma, Esteve and ROVI. SQ reports personal fees and nonfinancial support from GSK, AZ, Sanofi, Novartis, Mundipharma, Teva and Allergy Therapeutics. JSastre declares personal fees from Novartis, GSK, Faes Farma, Sanofi and Mundipharma. MS reports personal fees and/or grants from ASIT Biotech.sa, ALK, Regeneron, Merck, Immune Tolerance Network and Allergopharma. CC‐A reports funding from EAACI. OP received research grants from Inmunotek SL and Novartis; received fees for giving scientific lectures from Allergy Therapeutics, Amgen, AstraZeneca, Diater, GSK, Inmunotek SL, Novartis, Sanofi Genzyme and Stallergenes; and participated in advisory boards from Novartis and Sanofi Genzyme. MJ reports personal fees from ALK‐Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, HAL, AstraZeneca, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Janssen, MedImmune and Chiesi. All other authors have no conflict of interest within the scope of the submitted work.
The main goal in the management of patients with severe asthma is achieving disease control and reducing risk of attacks while avoiding harm from controller therapies.1,2 Despite extensive efforts, there is still a small proportion of patients with severe asthma insufficiently controlled with the current medications, with a significant burden due to high morbidity and costs.3-8 Current guidelines support the targeted approach in uncontrolled severe asthma, and several biologicals are approved for use in these patients.1,2 IL-4 and IL-13 are key cytokines in driving the initiation and chronicity of type 2 (T2) inflammation, an important inflammatory pathway in severe asthma.9-11 Dupilumab is a fully human anti-IL-4 receptor ? (IL-4R?) monoclonal antibody that blocks both IL-4- and IL-13-mediated signalling pathways. It has been recently approved for adults and adolescents 12?years and older as add-on maintenance treatment for severe asthma. According to the European Medicines Agency (EMA), dupilumab is recommended for severe asthma with T2 inflammation characterized by raised blood eosinophils and/or fractional exhaled nitric oxide (FeNO), inadequately controlled with high-dose inhaled corticosteroids (ICS) plus another maintenance treatment.12 The US Food and Drug Administration (FDA) recommends dupilumab for an eosinophilic phenotype or for oral corticosteroid (OCS)?dependent asthma.13 The European Academy of Allergy and Clinical Immunology (EAACI) is developing clinical practice guidelines for the use of biologicals in patients with severe asthma. To inform key clinical recommendations, a systematic review (SR) evaluated the effectiveness and safety of dupilumab for patients with uncontrolled severe asthma.
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