A 45-year-old woman with allergic rhinitis and eosinophilic chronic rhinosinusitis presents with recurrent bilateral nasal polyps 8 months after endoscopic sinus surgery. Imaging shows new polyp formation. What is the drug of choice to reduce recurrence and prevent further polyp growth?

Explanation

## Biologic Therapy for Recurrent Nasal Polyps in Eosinophilic CRS **Key Point:** Dupilumab (a monoclonal antibody against IL-4 receptor α) is indicated for recurrent nasal polyps in patients with eosinophilic chronic rhinosinusitis (CRS) or allergic phenotype, especially after surgical failure or rapid recurrence. ### Pathophysiology of Eosinophilic CRS with Polyps - **Th2-driven inflammation**: IL-4 and IL-13 drive eosinophilic infiltration and mucus hypersecretion - **Polyp formation**: Eosinophilic inflammation → stromal edema → polyp growth - **Rapid recurrence**: Intranasal corticosteroids alone may be insufficient in high eosinophil phenotype ### Dupilumab Mechanism & Evidence - **Target**: IL-4 receptor α (shared by IL-4 and IL-13 signaling pathways) - **Effect**: Blocks Th2 differentiation, reduces eosinophil recruitment, decreases polyp size and recurrence - **Clinical trials** (LIBERTY NP studies): Dupilumab reduced polyp recurrence by ~50% and improved nasal obstruction scores in patients with prior surgery or inadequate response to intranasal corticosteroids - **Dosing**: 300 mg SC every 2 weeks (after 600 mg loading dose) **High-Yield:** Dupilumab is now FDA-approved and recommended by major guidelines (AAO-HNS, EPOS) for: - Recurrent nasal polyps after ESS - Inadequate response to intranasal corticosteroids - Eosinophilic CRS phenotype ### Comparison of Biologic Options | Agent | Target | Indication for Polyps | Evidence | |---|---|---|---| | **Dupilumab** | IL-4Rα | Recurrent polyps, eosinophilic CRS, allergic phenotype | Strong (LIBERTY NP trials) | | **Omalizumab** | IgE | Allergic rhinitis, severe asthma | Weak for polyp recurrence; not approved for CRS | | **Mepolizumab** | IL-5 | Severe eosinophilic asthma | Limited polyp data; not first-line for CRS | | **Reslizumab** | IL-5 | Eosinophilic asthma | Limited polyp data | **Clinical Pearl:** Dupilumab is superior to omalizumab for recurrent polyps because it blocks both IL-4 and IL-13 signaling, whereas omalizumab only targets IgE-mediated allergy. Many patients with eosinophilic CRS have non-allergic eosinophilic inflammation. ### Why Intranasal Corticosteroids Alone Are Insufficient Here - Patient had **recurrence 8 months post-ESS** despite presumed intranasal corticosteroid use - Suggests **high eosinophil phenotype** resistant to topical steroids - Requires systemic Th2 blockade (dupilumab) to suppress polyp recurrence **Warning:** Do not confuse omalizumab (anti-IgE) with dupilumab (anti-IL-4Rα). Omalizumab is indicated for allergic asthma and urticaria, NOT for eosinophilic CRS or recurrent polyps. [cite:Harrison 21e Ch 409; AAO-HNS Clinical Practice Guideline 2021]