Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma


Por: 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, Makela, M, Martin, IH, Nair, P, O'Mahony, L, Papadopoulos, NG, Papi, A, Park, HS, de Llano, LP, Posso, M, Rocha, C, Quirce, S, Sastre, J, Shamji, M, Song, Y, Steiner, C, Schwarze, J, Alonso-Coello, P, Palomares, O, Jutel, M

Publicada: 1 may 2020 Ahead of Print: 1 feb 2020
Resumen:
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.

Filiaciones:
Agache, I:
 Transylvania Univ, Fac Med, 2A Pictor Ion Andreescu, Brasov 500051, Romania

Beltran, J:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

Akdis, C:
 Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland

 Christine Kuhne Ctr Allergy Res & Educ, Davos, Switzerland

Akdis, M:
 Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland

Canelo-Aybar, C:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

 CIBERESP, Madrid, Spain

Canonica, GW:
 IRCCS, Personalized Med Asthma & Allergy, Humanitas Clin & Res Ctr, Rozzano, Italy

Casale, T:
 Univ S Florida, Div Allergy & Immunol, Morsani Coll Med, Tampa, FL 33620 USA

Chivato, T:
 Univ CEU San Pablo, Sch Med, Madrid, Spain

Corren, J:
 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

Del Giacco, S:
 Univ Cagliari, Dept Med Sci & Publ Hlth, Cagliari, Italy

Eiwegger, T:
 Hosp Sick Children, Res Inst, Translat Med Program, Toronto, ON, Canada

 Univ Toronto, Dept Immunol, Toronto, ON, Canada

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

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

Firinu, D:
 Univ Cagliari, Dept Med Sci & Publ Hlth, Cagliari, Italy

Gern, JE:
 Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA

Hamelmann, E:
 Klin Kinder & Jugendmed Kinderzentrum Bethel, Bielefeld, Germany

Hanania, N:
 Baylor Coll Med, Sect Pulm Crit Care & Sleep Med, Houston, TX 77030 USA

Makela, M:
 Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland

 Univ Helsinki, Helsinki, Finland

Martin, IH:
 Hosp Univ La Paz, Dept Allergy, Madrid, Spain

Nair, P:
 McMaster Univ, Dept Med, Div Respirol, Hamilton, ON, Canada

 St Josephs Healthcare, Firestone Inst Resp Hlth, Hamilton, ON, Canada

O'Mahony, L:
 Univ Coll Cork, Dept Med, APC Microbiome Ireland, Cork, Ireland

 Univ Coll Cork, Dept Microbiol, APC Microbiome Ireland, Cork, Ireland

Papadopoulos, NG:
 Univ Manchester, Div Infect Immun & Resp Med, Manchester, Lancs, England

 Natl Kapodistrian Univ Athens, Allergy Dept, Pediat Clin 2, Athens, Greece

Papi, A:
 Univ Ferrara, Res Ctr Asthma & COPD, Dept Med Sci, Ferrara, Italy

Park, HS:
 Ajou Univ, Dept Allergy & Clin Immunol, Suwon, South Korea

de Llano, LP:
 Hosp Lucus Augusti, Dept Resp Med, Lugo, Spain

Posso, M:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

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

Rocha, C:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

Quirce, S:
 Univ Autonoma Madrid, La Paz Univ Hosp, CIBER Resp Dis CIBERES, Dept Allergy,IdiPAZ, Madrid, Spain

Sastre, J:
 Univ Autonoma Madrid, Fac Med, Madrid, Spain

Shamji, M:
 Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, Allergy & Clin Immunol Inflammat Repair Dev, London, England

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

Song, Y:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

Steiner, C:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

Schwarze, J:
 Univ Edinburgh, Ctr Inflammat Res Child Life & Hlth, Edinburgh, Midlothian, Scotland

Alonso-Coello, P:
 Biomed Res Inst St Pau IIB St Pau, Iberoamer Cochrane Ctr, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

 CIBERESP, Madrid, Spain

Palomares, O:
 Univ Complutense Madrid, Chem Sch, Dept Biochem & Mol Biol, Madrid, Spain

Jutel, M:
 Univ Wroclaw, Dept Clin Immunol, Wroclaw, Poland

 ALL MED Med Res Inst, Wroclaw, Poland
ISSN: 01054538





ALLERGY
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Reino Unido
Tipo de documento: Article
Volumen: 75 Número: 5
Páginas: 1023-1042
WOS Id: 000515298100001
ID de PubMed: 32034960
imagen Green Accepted, Bronze

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