Dupilumab, approved for moderate-to-severe atopic dermatitis and asthma, blocks the shared receptor subunit for IL-4 and IL-13. This shared subunit is:

• A IL-13Rα2, the decoy receptor that sequesters IL-13 away from signalling receptors
• B JAK1, the kinase shared downstream of both IL-4 and IL-13 signalling
• C STAT6, the transcription factor common to both IL-4 and IL-13 signalling pathways
• D IL-4Rα (interleukin-4 receptor alpha chain), which dimerises with gamma-c chain (Type I receptor) or IL-13Rα1 (Type II receptor) ✓

Explanation

Dupilumab is a monoclonal antibody that binds the IL-4 receptor alpha (IL-4Rα) chain, which is the shared component of both the Type I IL-4 receptor (IL-4Rα + common gamma chain, found on lymphocytes) and Type II IL-4/IL-13 receptor (IL-4Rα + IL-13Rα1, found on non-haematopoietic cells including airway epithelium and keratinocytes). By blocking IL-4Rα, dupilumab simultaneously inhibits IL-4 signalling via both receptor types and IL-13 signalling via the Type II receptor. This dual blockade of the key Th2 cytokines explains its efficacy in atopic/eosinophilic diseases. IL-13Rα2 is a decoy receptor; JAK1 and STAT6 are intracellular and not directly targeted by dupilumab.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.