Mechanisms of Dupilumab

Abstract

The Th2 cytokines interleukin 4 (IL‐4) and IL‐13 and the heterodimeric IL‐4 receptor (IL‐4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL‐4 receptor alpha chain (IL‐4Rα), common to both IL‐4R complexes: type 1 (IL‐4Rα/γc; IL‐4 specific) and type 2 (IL‐4Rα/IL‐13Rα1; IL‐4 and IL‐13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL‐4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.

Dupilumab as a useful treatment option for prurigo nodularis in an elderly patient with atopic diathesis

“…1,2 Dupilumab is a monoclonal antibody that inhibits IL (interleukin)-4 and IL-13, resulting in the downregulation of epidermal proliferation and inflammatory mediators, consequently promoting normalization of the skin. 3 Clinical trials have demonstrated the efficacy of dupilumab treatment in AD and supported an acceptable side effect profile. 1,4 There is currently limited evidence for its use in real-world clinical practice.…”

New and Emerging Systemic Treatments for Atopic Dermatitis

“…ILC2s are tissue-resident lymphocytes that do not derive from either the T cell or B cell lineage. Along with T H 2 cells, ILC2s produce a large amount of the pro-inflammatory cytokine IL-13 [1,11].…”

“…When IL-4 or IL-13 binds to either type (I or II) of the IL-4 receptor complex, an associated Janus kinase (JAK) protein-JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)is phosphorylated and activated ( Fig. 1) [11]. Activation of JAK proteins leads to a phosphorylation cascade, which ultimately activates the transcription factors signal transducer and activator of transcription 6 (STAT6) and signal transducer and activator of transcription 3 (STAT3) [11].…”

Understanding the response to asthma biological therapy

“…Neutrophil/eosinophil pathways were especially up‐regulated in non‐responders and did not change with omalizumab therapy. Understanding response to therapy at this endotype level has a potential to help us better personalize therapy for severe asthma 5 …”