Targeting the IL-5 pathway in eosinophilic asthma: A comparison of anti-IL-5 versus anti-IL-5 receptor agents

Allergy. 2024 Nov;79(11):2943-2952. doi: 10.1111/all.16346. Epub 2024 Oct 12.

Abstract

Eosinophilic asthma is characterized by frequent exacerbations, poor symptom control and accelerated lung function decline. It is now recognized that the immune response underlying eosinophilic asthma involves a complex network of interconnected pathways from both the adaptive and innate immune systems. Within this response, interleukin-5 (IL-5) plays a central role in eosinophil differentiation, activation and survival and has emerged as a key target for therapies treating severe asthma. The monoclonal antibodies mepolizumab and reslizumab target the ligand IL-5, preventing its interaction with eosinophils; in contrast, benralizumab binds to the IL-5 receptor (IL-5R), preventing IL-5 from binding and leading to substantially greater eosinophil reduction by enhanced antibody-dependent cell-mediated cytotoxicity. Although no direct head-to-head clinical trials of asthma have been published to formally evaluate the clinical significance of these different therapeutic approaches, the potential benefits of partial versus complete eosinophil depletion continue to remain an important area of study and debate. Here, we review the existing real-world and clinical study data of anti-IL-5/anti-IL-5R therapies in severe eosinophilic asthma.

Keywords: IL‐5; IL‐5R; asthma; benralizumab; eosinophil; mepolizumab; reslizumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Asthmatic Agents* / pharmacology
  • Anti-Asthmatic Agents* / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Asthma* / drug therapy
  • Asthma* / immunology
  • Asthma* / metabolism
  • Eosinophilia / drug therapy
  • Eosinophilia / immunology
  • Eosinophils* / immunology
  • Eosinophils* / metabolism
  • Humans
  • Interleukin-5* / antagonists & inhibitors
  • Interleukin-5* / metabolism
  • Molecular Targeted Therapy
  • Receptors, Interleukin-5* / antagonists & inhibitors
  • Receptors, Interleukin-5* / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Interleukin-5
  • Receptors, Interleukin-5
  • Anti-Asthmatic Agents
  • IL5 protein, human
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal

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