What is the best treatment approach for a patient with severe eosinophilic asthma and uncontrolled rhinosinusitis?

Mepolizumab is the Best Treatment for Severe Eosinophilic Asthma with Uncontrolled Rhinosinusitis

For a patient with severe eosinophilic asthma and uncontrolled rhinosinusitis with nasal polyps who has failed conventional therapy, mepolizumab 100 mg subcutaneously every 4 weeks is the optimal treatment approach.

Patient Assessment and Classification

This 42-year-old woman presents with:

• Severe eosinophilic asthma (symptoms most days despite proper inhaler adherence)
• Two serious asthma exacerbations in the past year (one requiring hospitalization)
• Chronic rhinosinusitis with nasal polyps (uncontrolled symptoms)
• Blood eosinophil count of 350 cells/μL
• Negative allergy testing
• Current treatment: budesonide-formoterol and triamcinolone nasal spray

This clinical picture represents type 2 inflammation affecting both upper and lower airways, with evidence of corticosteroid resistance despite appropriate therapy.

Treatment Recommendation Algorithm

1. First-line biologic therapy: Mepolizumab

   • Dosage: 100 mg subcutaneously once every 4 weeks 1
   • Indication: FDA-approved for both severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps 1
   • Evidence: Real-world data shows 79.7% reduction in clinically significant exacerbations in patients with both conditions 2

2. Continue current controller medications

   • Maintain budesonide-formoterol inhaler
   • Continue triamcinolone nasal spray
   • Consider optimizing intranasal corticosteroid delivery technique

3. Assess response after 3-6 months

   • Evaluate asthma control (symptoms, exacerbations)
   • Assess nasal symptoms using validated tools (e.g., SNOT-22)
   • Monitor blood eosinophil count

Evidence Supporting Mepolizumab

Mepolizumab targets interleukin-5 (IL-5), a key cytokine in eosinophilic inflammation that affects both the upper and lower airways. This makes it particularly effective for patients with the dual diagnosis of severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps.

The most recent evidence from a large real-world pooled analysis of 1,037 patients demonstrated that mepolizumab provides:

• 79.7% reduction in clinically significant exacerbations in patients with both asthma and CRSwNP
• 30% greater benefit in patients with both conditions compared to those with asthma alone
• Significant reduction in oral corticosteroid use
• Improvement in lung function and asthma control test scores 2

The FDA has specifically approved mepolizumab for both:

• Add-on maintenance treatment of severe asthma with an eosinophilic phenotype
• Add-on maintenance treatment of chronic rhinosinusitis with nasal polyps 1

Alternative Considerations

If mepolizumab is ineffective after 3-6 months, consider:

1. Alternative biologics:

   • Dupilumab (targets IL-4/IL-13 pathway)
   • Benralizumab (targets IL-5 receptor)
   • Omalizumab (for patients with allergic component, though this patient has negative allergy testing) 3

2. Surgical intervention:

   • Functional endoscopic sinus surgery may be considered for refractory rhinosinusitis not responding to medical therapy 4

Pitfalls and Caveats

• Avoid abrupt discontinuation of inhaled corticosteroids when initiating mepolizumab, as this may lead to worsening symptoms 1
• Monitor for hypersensitivity reactions including anaphylaxis, angioedema, bronchospasm, and rash, particularly with initial doses 1
• Consider helminth infection screening in patients from endemic areas, as anti-IL-5 therapy may impair anti-parasitic immune responses 1
• Response may differ between upper and lower airway symptoms - some patients achieve better control of asthma than rhinosinusitis symptoms 5
• Mepolizumab is not for acute symptom relief and should not be used to treat acute bronchospasm or status asthmaticus 1

Conclusion

This patient's presentation of severe eosinophilic asthma with uncontrolled rhinosinusitis and nasal polyps despite conventional therapy represents a clear indication for biologic therapy targeting type 2 inflammation. Mepolizumab offers the advantage of FDA approval for both conditions and demonstrated effectiveness in reducing exacerbations, improving symptoms, and reducing corticosteroid requirements in patients with this dual diagnosis.