What are the criteria for initiating mepolizumab in an adult with chronic rhinosinusitis that is refractory to maximal intranasal corticosteroids, requires multiple courses of systemic corticosteroids, demonstrates an eosinophilic phenotype (blood eosinophils ≥150 cells/µL or tissue eosinophilia), may have comorbid severe eosinophilic asthma, and after exclusion of other causes such as fungal infection, immunodeficiency, or systemic disease?

Criteria to Start Mepolizumab for Chronic Rhinosinusitis

Initiate mepolizumab 100 mg subcutaneously every 4 weeks in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) who remain uncontrolled despite maximal intranasal corticosteroids and have either required systemic corticosteroids or are candidates for surgery. 1

Essential Eligibility Criteria

Disease Severity Requirements

• Uncontrolled CRSwNP defined as persistent clinically relevant sinonasal symptoms (overall symptom severity, nasal obstruction, and loss of smell) despite treatment 2
• Severe bilateral nasal polyps documented on nasal endoscopy 3
• Failed maximal medical therapy with intranasal corticosteroids 1
• Either requires systemic corticosteroids for control OR is a surgical candidate 1, 4

Biomarker Considerations

Blood eosinophil count is NOT a strict requirement for mepolizumab initiation in CRSwNP. The pivotal SYNAPSE trial and FDA approval do not mandate a specific eosinophil threshold 1, 3. However, the evidence shows:

• Mepolizumab demonstrated efficacy across all baseline blood eosinophil count (BEC) subgroups, including patients with <150 cells/μL 3
• 50.7% of patients with BEC <300 cells/μL achieved ≥1-point improvement in nasal polyp score versus 29.0% with placebo 3
• The drug works through IL-5 blockade targeting eosinophilic type-2 inflammation, making it mechanistically appropriate even without elevated peripheral eosinophils 2

Clinical pearl: While eosinophilia (≥150 cells/μL) is commonly present and supports the diagnosis of eosinophilic CRS 2, do not withhold mepolizumab based solely on a low peripheral eosinophil count if the patient meets other severity criteria.

Comorbidity Assessment

Favorable Indicators (Not Requirements)

• Comorbid severe eosinophilic asthma - particularly strong evidence for dual benefit 5, 6
• Aspirin-exacerbated respiratory disease (AERD) - 51.1% achieved ≥1-point polyp score improvement versus 20.6% placebo 3
• Type-2 comorbidities present in 93.5% of real-world mepolizumab users 7

Important: Mepolizumab works effectively in CRSwNP regardless of asthma status. In patients without comorbid asthma or AERD, similar improvements in polyp size and nasal obstruction were observed 3.

Exclusion Considerations

Before initiating mepolizumab, rule out:

• Fungal sinusitis (allergic fungal rhinosinusitis)
• Immunodeficiency disorders
• Systemic vasculitis (though mepolizumab is approved for EGPA and can treat both conditions simultaneously 6)
• Helminth infections - treat parasitic infections before starting therapy 1

Phenotype Flexibility

Mepolizumab can be considered in CRS without nasal polyps (CRSsNP) with eosinophilic endotype, though this is off-label. Real-world data shows 29.6% of mepolizumab users had CRSsNP with significant reductions in eosinophilia and radiographic disease burden 7. This represents an endotype-driven rather than phenotype-driven approach.

Documentation Requirements

Prior to initiation, document:

• Nasal endoscopy with polyp scoring (Lund-Kennedy score) 8
• CT sinus imaging (Lund-Mackay score) 8, 7
• SNOT-22 symptom score for baseline quality of life 8
• History of systemic corticosteroid use (number of courses, total dose) 9
• Prior sinus surgeries and dates 8
• Blood eosinophil count (for monitoring, not exclusion) 8

Practical Algorithm

START mepolizumab if ALL of the following:

1. Severe bilateral CRSwNP confirmed by endoscopy
2. Uncontrolled symptoms despite ≥3 months of intranasal corticosteroids
3. AND either:
   • Required ≥2 systemic corticosteroid courses in past year, OR
   • Candidate for/failed endoscopic sinus surgery
4. Alternative diagnoses excluded

Blood eosinophils ≥150 cells/μL support the decision but are not mandatory 3

Common Pitfalls to Avoid

• Do not delay therapy waiting for "high enough" eosinophils - efficacy demonstrated across all BEC ranges 3
• Do not require surgical failure first - mepolizumab is appropriate for surgical candidates who prefer medical management 1
• Do not withhold in CRSsNP if eosinophilic endotype is suspected based on clinical features and biomarkers 7
• Do not use as monotherapy - mepolizumab is add-on to intranasal corticosteroids 1, 4

Real-World Outcomes

After mepolizumab initiation, expect:

• 67.9% complete remission with medical therapy alone 6
• Reduction in systemic corticosteroid use from 1.2 to 0.5 courses per patient per year 9
• 77% reduction in sinus surgery rate (rate ratio 0.23) 9
• Significant improvements by 3 months, sustained through 12+ months 10, 5

The evidence strongly supports mepolizumab as a disease-modifying therapy that reduces morbidity from both the disease itself and from systemic corticosteroid exposure, while potentially avoiding surgical intervention 9, 5.