Skip to main content
Top

Open Access 08-06-2024 | Mepolizumab | Review Article

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

Authors: Carlo Lombardi, Pasquale Comberiati, Erminia Ridolo, Marcello Cottini, Mona Rita Yacoub, Silvia Casagrande, Matteo Riccò, Marco Bottazzoli, Alvise Berti

Published in: Drugs

Login to get access

Abstract

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.
Literature
11.
go back to reference Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. SIROCCO Study Investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–27. https://doi.org/10.1016/S0140-6736(16)31324-1.CrossRefPubMed Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. SIROCCO Study Investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–27. https://​doi.​org/​10.​1016/​S0140-6736(16)31324-1.CrossRefPubMed
12.
go back to reference FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. CALIMA Study Investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41. https://doi.org/10.1016/S0140-6736(16)31322-8.CrossRefPubMed FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. CALIMA Study Investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41. https://​doi.​org/​10.​1016/​S0140-6736(16)31322-8.CrossRefPubMed
15.
go back to reference Agache I, Beltran J, Akdis C, Akdis M, Canelo-Aybar C, Canonica GW, et al. 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. Allergy. 2020;75(5):1023–42. https://doi.org/10.1111/all.14221.CrossRefPubMed Agache I, Beltran J, Akdis C, Akdis M, Canelo-Aybar C, Canonica GW, et al. 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. Allergy. 2020;75(5):1023–42. https://​doi.​org/​10.​1111/​all.​14221.CrossRefPubMed
25.
go back to reference Jackson DJ, Bacharier LB, Gergen PJ, Gagalis L, Calatroni A, Wellford S, et al. US National Institute of Allergy and Infectious Disease’s Inner City Asthma Consortium. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet. 2022;400(10351):502–11. https://doi.org/10.1016/S0140-6736(22)01198-9.CrossRefPubMedPubMedCentral Jackson DJ, Bacharier LB, Gergen PJ, Gagalis L, Calatroni A, Wellford S, et al. US National Institute of Allergy and Infectious Disease’s Inner City Asthma Consortium. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet. 2022;400(10351):502–11. https://​doi.​org/​10.​1016/​S0140-6736(22)01198-9.CrossRefPubMedPubMedCentral
32.
go back to reference Bleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52(4):1800936.CrossRefPubMedPubMedCentral Bleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52(4):1800936.CrossRefPubMedPubMedCentral
46.
go back to reference Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390–400. https://doi.org/10.1016/S2213-2600(17)30125-X.CrossRefPubMed Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390–400. https://​doi.​org/​10.​1016/​S2213-2600(17)30125-X.CrossRefPubMed
49.
go back to reference Panettieri RA Jr, Welte T, Shenoy KV, Korn S, Jandl M, Kerwin EM, et al. SOLANA Study Investigators. Onset of effect, changes in airflow obstruction and lung volume, and health-related quality of life improvements with benralizumab for patients with severe eosinophilic asthma: phase IIIb randomized, controlled trial (SOLANA). J Asthma Allergy. 2020;13:115–26. https://doi.org/10.2147/JAA.S240044. (Erratum in: J Asthma Allergy. 2020 Mar 13;13:135).CrossRefPubMedPubMedCentral Panettieri RA Jr, Welte T, Shenoy KV, Korn S, Jandl M, Kerwin EM, et al. SOLANA Study Investigators. Onset of effect, changes in airflow obstruction and lung volume, and health-related quality of life improvements with benralizumab for patients with severe eosinophilic asthma: phase IIIb randomized, controlled trial (SOLANA). J Asthma Allergy. 2020;13:115–26. https://​doi.​org/​10.​2147/​JAA.​S240044. (Erratum in: J Asthma Allergy. 2020 Mar 13;13:135).CrossRefPubMedPubMedCentral
56.
go back to reference Harrison TW, Chanez P, Menzella F, Canonica GW, Louis R, Cosio BG, et al. ANDHI Study investigators. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial. Lancet Respir Med. 2021;9(3):260–74. https://doi.org/10.1016/S2213-2600(20)30414-8.CrossRefPubMed Harrison TW, Chanez P, Menzella F, Canonica GW, Louis R, Cosio BG, et al. ANDHI Study investigators. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial. Lancet Respir Med. 2021;9(3):260–74. https://​doi.​org/​10.​1016/​S2213-2600(20)30414-8.CrossRefPubMed
60.
62.
go back to reference Bernstein JA, Virchow JC, Murphy K, Maspero JF, Jacobs J, Adir Y, et al. Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2020;8(5):461–74. https://doi.org/10.1016/S2213-2600(19)30372-.8.CrossRefPubMed Bernstein JA, Virchow JC, Murphy K, Maspero JF, Jacobs J, Adir Y, et al. Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2020;8(5):461–74. https://​doi.​org/​10.​1016/​S2213-2600(19)30372-.​8.CrossRefPubMed
89.
110.
go back to reference Mizuho N, Masaya S, Fumito A, Atsushi K, Hideki W, Naoto T. A pediatric case of relapsing eosinophilic granulomatosis with polyangiitis successfully treated with mepolizumab. Intern Med. 2019;58:3583–7.CrossRef Mizuho N, Masaya S, Fumito A, Atsushi K, Hideki W, Naoto T. A pediatric case of relapsing eosinophilic granulomatosis with polyangiitis successfully treated with mepolizumab. Intern Med. 2019;58:3583–7.CrossRef
115.
go back to reference Bandla M, Howard M, McNally A, Armstrong D, Simpson I, Mar A. Benralizumab: a novel treatment for the cutaneous features of paediatric eosinophilic granulomatosis with polyangiitis (pEGPA). Australas J Dermatol. 2023;64:404–7.CrossRefPubMed Bandla M, Howard M, McNally A, Armstrong D, Simpson I, Mar A. Benralizumab: a novel treatment for the cutaneous features of paediatric eosinophilic granulomatosis with polyangiitis (pEGPA). Australas J Dermatol. 2023;64:404–7.CrossRefPubMed
119.
120.
127.
go back to reference Farruggia P, D’Angelo P, Acquaviva A, Trizzino A, Tucci F, Cilloni D, et al. Hypereosinophilic syndrome in childhood: clinical and molecular features of two cases. Pediatr Hematol Oncol. 2009;26(3):129–35.CrossRefPubMed Farruggia P, D’Angelo P, Acquaviva A, Trizzino A, Tucci F, Cilloni D, et al. Hypereosinophilic syndrome in childhood: clinical and molecular features of two cases. Pediatr Hematol Oncol. 2009;26(3):129–35.CrossRefPubMed
Metadata
Title
Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan
Authors
Carlo Lombardi
Pasquale Comberiati
Erminia Ridolo
Marcello Cottini
Mona Rita Yacoub
Silvia Casagrande
Matteo Riccò
Marco Bottazzoli
Alvise Berti
Publication date
08-06-2024
Publisher
Springer International Publishing
Published in
Drugs
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-024-02037-0