Dupilumab is a biologic used in severe eosinophilic asthma and atopic dermatitis. Its mechanism targets which upstream cytokine signalling pathway?

• A Anti-IL-5 that blocks eosinophil survival
• B Anti-IL-4Ralpha monoclonal antibody that blocks signalling of both IL-4 and IL-13 via the type I and type II IL-4 receptor complex ✓
• C Anti-IgE that prevents mast cell degranulation
• D Anti-IL-33 that blocks epithelial alarmin signalling

Explanation

Dupilumab is a fully human monoclonal antibody targeting the IL-4 receptor alpha (IL-4Ralpha) subunit. IL-4Ralpha is a shared subunit of the type I IL-4 receptor (IL-4Ralpha + gamma-c chain, expressed on lymphocytes) and the type II receptor (IL-4Ralpha + IL-13Ralpha1, expressed on non-haematopoietic cells). By blocking IL-4Ralpha, dupilumab simultaneously inhibits signalling from both IL-4 and IL-13 — the key Th2 cytokines that drive allergic inflammation, IgE class switching, mucus hypersecretion, and airway hyperresponsiveness. This is mechanistically upstream of mepolizumab/benralizumab (anti-IL-5/IL-5R) and omalizumab (anti-IgE).

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

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Written and medically reviewed by the StethoPrep medical team.