Dupilumab Treatment for Nasal Polyps
Dupilumab is the first-line monoclonal antibody treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) in patients with inadequately controlled disease despite standard therapies. 1
Indications and Patient Selection
Dupilumab is FDA-approved as an add-on maintenance treatment for adult and pediatric patients aged 12 years and older with inadequately controlled CRSwNP 2. Candidates for dupilumab therapy typically include patients who:
- Have severe CRSwNP that is inadequately controlled with intranasal corticosteroids
- Have recurrent nasal polyps despite surgical intervention
- Require systemic corticosteroids or surgery for polyp control
- Have comorbid type 2 inflammatory conditions (e.g., asthma)
Mechanism of Action
Dupilumab is a fully human monoclonal antibody that:
- Targets the interleukin-4 receptor α (IL-4Rα) subunit
- Blocks signaling of both IL-4 and IL-13, key drivers of type 2 inflammation
- Reduces local type 2 inflammatory biomarkers in nasal polyp tissue 3
Efficacy
Dupilumab demonstrates significant improvements in multiple outcome measures:
- Nasal polyp score (NPS): Reduction of -1.79 (95% CI -2.01 to -1.56) compared to placebo 1
- Sinonasal symptoms: Significant improvement in SNOT-22 scores by -19.61 points (95% CI -22.53 to -16.69) 1
- Nasal congestion: Reduction of -0.86 (95% CI -0.98 to -0.75) 1
- Smell function: Improvement in UPSIT score by 10.83 points (95% CI 9.59 to 12.08) 1
- CT imaging: Reduction in Lund-Mackay scores by -1.50 (SMD) 1
- Reduced need for surgery: Fewer patients requiring nasal polyp surgery 4
- Reduced systemic corticosteroid use: Decreased dependency on oral steroids 4
Dosing and Administration
- Standard dose: 300 mg subcutaneous injection every 2 weeks 2
- Initial dose: 600 mg (two 300 mg injections at different injection sites) 2
- Administration sites: Thigh, abdomen (except 2 inches around navel), or upper arm 2
- Administration guidance: Self-administration or caregiver administration after proper training 2
Special Populations
Dupilumab is effective regardless of:
- Comorbid asthma: Improves both upper and lower airway outcomes in patients with CRSwNP and asthma 5
- Allergic rhinitis status: Similar efficacy in patients with or without comorbid allergic rhinitis 6
- Eosinophil levels: Efficacy unaffected by eosinophilic status 7
- Previous surgery: Effective in patients with history of nasal polyp surgery 1
Safety Profile
Dupilumab is generally well-tolerated with:
- Most common adverse events: nasopharyngitis, headache, injection-site erythema 5
- No significant safety concerns specific to CRSwNP patients 1
- Unlike in atopic dermatitis, conjunctivitis is not commonly observed in CRSwNP patients treated with dupilumab 1
Clinical Pearls and Caveats
- Vaccination: Consider completing all age-appropriate vaccinations before initiating dupilumab 2
- Monitoring: Regular assessment of nasal symptoms, polyp size, and quality of life measures
- Continuation: Long-term therapy is typically required as discontinuation may lead to recurrence
- Comorbidities: Particularly beneficial in patients with comorbid asthma, as it improves both upper and lower airway disease 5
Comparison to Other Biologics
- Dupilumab is currently the only monoclonal antibody approved for CRSwNP treatment 1
- Mepolizumab (anti-IL-5) has shown efficacy but is not yet approved for CRSwNP 1
- The EPOS2020 guideline specifically recommends dupilumab for patients with CRSwNP fulfilling criteria for monoclonal antibody treatment 1
Dupilumab represents a significant advancement in the treatment of CRSwNP, offering substantial improvements in polyp size, symptoms, and quality of life for patients with inadequately controlled disease.