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

被引：68

作者：

Agache, Ioana ^{[1
]}

Song, Yang ^{[2
]}

Rocha, Claudio ^{[2
]}

Beltran, Jessica ^{[2
]}

Posso, Margarita ^{[2
,3
]}

Steiner, Corinna ^{[2
]}

Alonso-Coello, Pablo ^{[2
,4
]}

Akdis, Cezmi ^{[5
,6
]}

Akdis, Mubeccel ^{[5
,6
]}

Canonica, Giorgio Walter ^{[7
]}

Casale, Thomas ^{[8
]}

Chivato, Tomas ^{[9
]}

Corren, Jonathan ^{[10
]}

del Giacco, Stefano ^{[11
]}

Eiwegger, Thomas ^{[12
,13
,14
,15
]}

Firinu, Davide ^{[11
]}

Gern, James E. ^{[16
]}

Hamelmann, Eckard ^{[17
]}

Hanania, Nicola ^{[18
]}

Makela, Mika ^{[19
,20
]}

Martin, Irene Hernandez ^{[21
]}

Nair, Parameswaran ^{[22
,23
]}

O'Mahony, Liam ^{[24
,25
]}

Papadopoulos, Nikolaos G. ^{[26
,27
]}

Papi, Alberto ^{[28
]}

Park, Hae-Sim ^{[29
]}

de Llano, Luis Perez ^{[30
]}

Quirce, Santiago ^{[31
]}

Sastre, Joaquin ^{[32
]}

Shamji, Mohamed ^{[33
,34
]}

Schwarze, Jurgen ^{[35
]}

Canelo-Aybar, Carlos ^{[2
,4
]}

Palomares, Oscar ^{[36
]}

Jutel, Marek ^{[37
,38
]}

机构：

[1] Transylvania Univ, Fac Med, Brasov, Romania

[2] Biomed Res Inst St Pau IIB St Pau, Dept Clin Epidemiol & Publ Hlth, Iberoamer Cochrane Ctr, Barcelona, Spain

[3] IMIM Hosp del Mar Med Res Inst, Dept Epidemiol & Evaluat, Barcelona, Spain

[4] CIBERESP, Barcelona, Spain

[5] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland

[6] Christine Kuhne Ctr Allergy Res & Educ, Davos, Switzerland

[7] IRCCS, Humanitas Clin & Res Ctr, Personalized Med Asthma & Allergy, Rozzano, Italy

[8] Univ S Florida, Morsani Coll Med, Div Allergy & Immunol, Tampa, FL 33620 USA

[9] Univ CEU San Pablo, Sch Med, Madrid, Spain

[10] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[11] Univ Cagliari, Dept Med Sci & Publ Hlth, Monserrato, Italy

[12] Hosp Sick Children, Res Inst, Translat Med Program, Toronto, ON, Canada

[13] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[14] Univ Toronto, Hosp Sick Children, Food Allergy & Anaphylaxis Program, Div Immunol & Allergy,Dept Paediat, Toronto, ON, Canada

[15] Univ Toronto, Hosp Sick Children, Food Allergy & Anaphylaxis Program, Div Immunol & Allergy,Dept Immunol, Toronto, ON, Canada

[16] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA

[17] Kinderzentrum Bethel, Klin Kinder & Jugendmed, Bielefeld, Germany

[18] Baylor Coll Med, Sect Pulm Crit Care & Sleep Med, Houston, TX 77030 USA

[19] Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland

[20] Univ Helsinki, Helsinki, Finland

[21] Hosp Univ La Paz, Dept Allergy, Madrid, Spain

[22] McMaster Univ, Dept Med, Div Respirol, Hamilton, ON, Canada

[23] St Josephs Healthcare, Firestone Inst Resp Hlth, Hamilton, ON, Canada

[24] Univ Coll Cork, APC Microbiome Ireland, Dept Med, Cork, Ireland

[25] Univ Coll Cork, APC Microbiome Ireland, Dept Microbiol, Cork, Ireland

[26] Univ Manchester, Div Infect Immun & Resp Med, Manchester, Lancs, England

[27] Natl Kapodistrian Univ Athens, Pediat Clin 2, Dept Allergy, Athens, Greece

[28] Univ Ferrara, Res Ctr Asthma & COPD, Dept Med Sci, Ferrara, Italy

[29] Ajou Univ, Dept Allergy & Clin Immunol, Suwon, South Korea

[30] Hosp Lucus Augusti, Dept Resp Med, Lugo, Spain

[31] Univ Autonoma Madrid, CIBER Resp Dis CIBERES, La Paz Univ Hosp, IdiPAZ,Dept Allergy, Madrid, Spain

[32] Univ Autonoma Madrid, Fac Med, Madrid, Spain

[33] Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, Allergy & Clin Immunol, Inflammat, London, England

[34] Asthma UK Ctr Allerg Mech Asthma, Imperial Coll NIHR Biomed Res Ctr, London, England

[35] Univ Edinburgh, Ctr Inflammat Res Child Life & Hlth, Edinburgh, Midlothian, Scotland

[36] Univ Complutense Madrid, Sch Chem, Dept Biochem & Mol Biol, Madrid, Spain

[37] Wroclaw Med Univ, Dept Clin Immunol, Wroclaw, Poland

[38] ALL MED Med Res Inst, Wroclaw, Poland

来源：

ALLERGY | 2020年 / 75卷 / 05期

关键词：

cost-effectiveness; dupilumab; exacerbations; oral corticosteroids; severe asthma; WILLINGNESS-TO-PAY; ECONOMIC EVALUATIONS; QUALITY; BURDEN; INFORMATION; SURROGATES; CONSENSUS; EURONHEED; GRADE; FENO;

D O I：

10.1111/all.14268

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor alpha, 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.

引用

页码：1058 / 1068

页数：11