Dupilumab is a monoclonal antibody used in moderate-to-severe asthma with eosinophilic or type 2 inflammation. It targets which cytokine signalling pathway?

• A Blocks IL-5 receptor α-chain on eosinophils, reducing eosinophil survival and activation
• B Neutralises IgE, preventing mast cell and basophil degranulation
• C Blocks the shared IL-4Rα receptor subunit, inhibiting both IL-4 (Th2 differentiation) and IL-13 (goblet cell hyperplasia, airway hyperresponsiveness) signalling simultaneously ✓
• D Blocks TSLP (thymic stromal lymphopoietin) upstream of Th2 polarisation

Explanation

Dupilumab is a fully human IgG4 monoclonal antibody that binds IL-4Rα, the shared alpha subunit of both the IL-4 receptor (type I, IL-4Rα/γc) and the IL-13 receptor (type II, IL-4Rα/IL-13Rα1). By blocking this shared subunit, dupilumab simultaneously inhibits both IL-4 and IL-13 signalling. IL-4 drives Th2 cell differentiation and IgE class switching; IL-13 promotes goblet cell hyperplasia, mucus overproduction, and airway smooth muscle hyperresponsiveness. This dual blockade distinguishes dupilumab from drugs targeting only IL-5 (mepolizumab, reslizumab) or only IgE (omalizumab). Dupilumab is approved for ≥12-year-olds with inadequately controlled moderate-to-severe asthma plus type 2 inflammation biomarkers.

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

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Written and medically reviewed by the StethoPrep medical team.