What is the recommended dose of Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Recommended Dose of Nucala (Mepolizumab) for EGPA

The recommended dose of Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (EGPA) is 300 mg administered subcutaneously every 4 weeks as three separate 100-mg injections. 1

Evidence-Based Dosing Recommendations

FDA-Approved Dosing

The FDA-approved dosing for EGPA is clear:

• 300 mg administered once every 4 weeks by subcutaneous injection
• Administered as 3 separate 100-mg injections into the upper arm, thigh, or abdomen
• Individual 100-mg injections should be administered at least 5 cm (approximately 2 inches) apart 1

Guideline Recommendations

Current guidelines from multiple authoritative sources support this dosing:

1. The 2021 American College of Rheumatology/Vasculitis Foundation guideline explicitly recommends mepolizumab 300 mg subcutaneously every 4 weeks for both remission induction and maintenance therapy in EGPA 2

2. The 2023 evidence-based guideline for EGPA management published in Nature Reviews Rheumatology confirms that 300 mg every 4 weeks is the approved dosage for EGPA 2

3. The 2024 EULAR recommendations for ANCA-associated vasculitis management recommend mepolizumab for induction of remission in patients with relapsing or refractory EGPA without active organ-threatening or life-threatening disease at a dose of 300 mg subcutaneously every 4 weeks 2

Clinical Evidence Supporting Efficacy

The pivotal MIRRA trial, which led to mepolizumab's approval for EGPA, used the 300 mg dose administered every 4 weeks. This trial demonstrated that mepolizumab:

• Resulted in significantly more weeks in remission
• Led to a higher proportion of participants achieving remission
• Allowed for reduced glucocorticoid use
• Had a favorable safety profile 3

Alternative Dosing Considerations

Interestingly, some evidence suggests that a lower dose of 100 mg every 4 weeks (the dose approved for severe eosinophilic asthma) may be effective in some EGPA patients:

• The 2023 guideline notes: "A lower initial dosage (100 mg every 4 weeks) can be considered, particularly in patients with limited respiratory manifestations; this dosage can subsequently be titrated up to 300 mg every 4 weeks in patients with an unsatisfactory response to treatment" 2

• A European multicenter observational study of 203 EGPA patients found comparable response rates between those receiving 100 mg (n=158) and 300 mg (n=33) every 4 weeks, with no significant differences in BVAS score reduction, prednisone dose reduction, or eosinophil count reduction 4

Clinical Decision Algorithm

1. For most EGPA patients: Start with the FDA-approved dose of 300 mg subcutaneously every 4 weeks

2. For patients with predominantly respiratory manifestations and limited systemic involvement:

   • Consider 100 mg subcutaneously every 4 weeks
   • Monitor response closely
   • Increase to 300 mg every 4 weeks if response is inadequate

3. For patients with organ-threatening or life-threatening disease:

   • Use the full 300 mg dose every 4 weeks
   • Consider additional immunosuppressive therapy as needed

Important Clinical Considerations

• Administer as three separate 100-mg injections at least 5 cm apart
• Monitor patients after administration due to potential for hypersensitivity reactions
• Expect clinical response within 3-6 months of initiation
• Continue to monitor disease activity using validated tools (e.g., BVAS)
• Aim to reduce glucocorticoid dose to ≤4 mg/day of prednisone or equivalent
• Consider specialist consultation (pulmonology, otolaryngology) for optimization of topical/inhaled therapies for respiratory manifestations

Conclusion

While lower doses (100 mg) have shown efficacy in some observational studies, particularly for respiratory manifestations, the FDA-approved dose and the dose supported by the highest quality evidence (MIRRA trial) remains 300 mg subcutaneously every 4 weeks for EGPA.