What are the approved indications for mepolizumab, including age and eosinophil count criteria, for severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis, and chronic rhinosinusitis with nasal polyps?

Approved Indications for Mepolizumab

Mepolizumab is FDA-approved for four distinct conditions: severe eosinophilic asthma (ages ≥6 years with blood eosinophils ≥150 cells/μL), eosinophilic granulomatosis with polyangiitis (EGPA, ages ≥6 years), chronic rhinosinusitis with nasal polyps (CRSwNP, ages ≥18 years), and hypereosinophilic syndrome (HES, ages ≥12 years). 1

Severe Eosinophilic Asthma

Patient Criteria:

• Age requirement: ≥6 years old 1
• Eosinophil threshold: Blood eosinophil count ≥150 cells/μL at treatment initiation OR ≥300 cells/μL within the previous 12 months 1
• Disease severity: Severe asthma inadequately controlled on high-dose inhaled corticosteroids plus additional controller medications 1

Dosing:

• Standard dose: 100 mg subcutaneously every 4 weeks 1
• This regimen significantly reduces clinically relevant asthma exacerbations, improves asthma control and quality of life, and enables oral corticosteroid dose reduction in steroid-dependent patients 2

Clinical outcomes: Mepolizumab provides durable clinical benefit over up to 84 weeks of therapy with acceptable tolerability, with headache being the most common adverse event 2

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Patient Criteria:

• Age requirement: ≥6 years old 3, 1
• Disease characteristics: Relapsing-refractory EGPA without organ- or life-threatening manifestations 3
• Specific indication: Particularly beneficial for patients requiring daily prednisone ≥7.5 mg for control of respiratory manifestations 3

Dosing Algorithm:

• FDA-approved dose: 300 mg subcutaneously every 4 weeks 3, 1
• Alternative lower dose: 100 mg every 4 weeks can be considered initially, particularly in patients with limited respiratory manifestations, then titrated to 300 mg every 4 weeks if response is unsatisfactory 3
• Real-world evidence demonstrates comparable efficacy between 100 mg and 300 mg dosing regimens, though this comes from retrospective analysis 3, 4

Treatment positioning: Mepolizumab is recommended in combination with glucocorticoids for both remission induction and maintenance therapy, with particular effectiveness for controlling asthma and ENT manifestations while enabling glucocorticoid sparing 3

Important caveat: Mepolizumab should NOT be used as first-line therapy for EGPA with organ- or life-threatening manifestations—these patients require rituximab or cyclophosphamide with high-dose glucocorticoids 3

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Patient Criteria:

• Age requirement: ≥18 years old 1
• Disease characteristics: Inadequate response to nasal corticosteroids 1

Dosing:

• Standard dose: 100 mg subcutaneously every 4 weeks 1

Clinical evidence: In severe eosinophilic asthma patients with concomitant CRSwNP, mepolizumab significantly reduces sino-nasal symptoms (SNOT-22 scores), decreases polyp growth (TENPS scores), and reduces nasal eosinophil percentage from 16.8% to 0.8% over 12 months 5

Hypereosinophilic Syndrome (HES)

Patient Criteria:

• Age requirement: ≥12 years old 1
• Disease characteristics: HES for ≥6 months without identifiable non-hematologic secondary cause 1

Dosing:

• Standard dose: 300 mg subcutaneously every 4 weeks 1

Key Clinical Considerations Across All Indications

Mechanism of action: Mepolizumab targets IL-5, the key cytokine responsible for eosinophil maturation, differentiation, and survival, thereby reducing both blood and tissue eosinophilia 6, 2

Common pitfalls to avoid:

• Do not use for acute asthma exacerbations or acute bronchospasm—mepolizumab is maintenance therapy only 1
• Screen for helminth infections before initiating therapy, particularly Strongyloides, which can cause fatal hyperinfection syndrome when immunosuppression is increased 7, 1
• Do not abruptly discontinue systemic corticosteroids upon starting mepolizumab—taper gradually under medical supervision 1
• Monitor for herpes zoster reactivation, as opportunistic infections have been reported 1

Contraindications: Hypersensitivity to mepolizumab or any excipient is the only absolute contraindication 1

Administration: All formulations are administered subcutaneously every 4 weeks, available as powder for injection vials, prefilled autoinjectors, and prefilled syringes 1