Medicine · Pulmonology (Asthma, COPD, Tuberculosis, Pneumonia, ILD, Pleural Diseases)

A 38-year-old woman with severe persistent asthma on high-dose ICS + LABA has blood eosinophils 680 cells/µL and total IgE 450 IU/mL. She has 3 exacerbations in the past year requiring oral steroids. She is started on mepolizumab. Mepolizumab's mechanism of action is:

  • A Anti-IgE monoclonal antibody reducing mast cell and basophil IgE-dependent activation
  • B Anti-IL-4Rα antibody blocking both IL-4 and IL-13 signalling
  • C Anti-IL-5 monoclonal antibody reducing eosinophil maturation and survival
  • D Anti-TSLP antibody preventing dendritic cell activation and Th2 skewing
Correct answer: C. Anti-IL-5 monoclonal antibody reducing eosinophil maturation and survival

Explanation

Mepolizumab is a humanised monoclonal antibody targeting IL-5, the primary cytokine responsible for eosinophil differentiation, maturation, activation, and survival. It is approved for severe eosinophilic asthma with blood eosinophils ≥150 cells/µL at initiation or ≥300 cells/µL in the past year. Anti-IgE therapy (omalizumab) targets IgE and is preferred for allergic asthma with high IgE. Dupilumab (anti-IL-4Rα) blocks IL-4 and IL-13. Tezepelumab (anti-TSLP) is a more upstream biologic. Reslizumab and benralizumab also target the IL-5 pathway (IL-5 and IL-5Rα respectively).

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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