Dupilumab: Mechanism of action, clinical, and translational science

Clin Transl Sci. 2024 Aug;17(8):e13899. doi: 10.1111/cts.13899.

Abstract

Allergic disease prevalence has increased globally with the subset of type 2 inflammatory diseases playing a substantial role. Type 2 inflammatory diseases may differ in clinical presentation, but they exhibit shared pathophysiology that is targeted by the unique pharmacology of dupilumab. Dupilumab binds to the interleukin (IL)-4 receptor alpha subunit (IL-4Rα) that blocks IL-4 and IL-13 signaling, two key drivers of type 2 inflammation. Herein, we review the mechanism of action and pharmacology of dupilumab, and the clinical evidence that led to the regulatory approvals of dupilumab for the treatment of numerous type 2 inflammatory diseases: atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Asthma / drug therapy
  • Asthma / immunology
  • Dermatitis, Atopic* / drug therapy
  • Dermatitis, Atopic* / immunology
  • Eosinophilic Esophagitis / drug therapy
  • Eosinophilic Esophagitis / immunology
  • Humans
  • Interleukin-13* / antagonists & inhibitors
  • Interleukin-13* / immunology
  • Interleukin-13* / metabolism
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / metabolism
  • Interleukin-4 Receptor alpha Subunit* / antagonists & inhibitors
  • Interleukin-4 Receptor alpha Subunit* / metabolism
  • Nasal Polyps / drug therapy
  • Nasal Polyps / immunology
  • Prurigo / drug therapy
  • Signal Transduction / drug effects
  • Sinusitis / drug therapy
  • Sinusitis / immunology
  • Translational Research, Biomedical*
  • Translational Science, Biomedical

Substances

  • dupilumab
  • Antibodies, Monoclonal, Humanized
  • Interleukin-4 Receptor alpha Subunit
  • Interleukin-13
  • Interleukin-4
  • IL4R protein, human
  • IL4 protein, human