Treatment Recommendation for EGPA with Relapsing Nonsevere Disease
For this patient with EGPA experiencing relapse with nonsevere disease manifestations (asthma and/or sinonasal disease) while receiving methotrexate, azathioprine, or mycophenolate mofetil, add mepolizumab (Nucala) to the current regimen rather than switching to an alternative conventional immunosuppressant. 1
Rationale for Mepolizumab Addition
The 2021 ACR/Vasculitis Foundation guideline specifically addresses this clinical scenario and conditionally recommends adding mepolizumab over adding omalizumab or switching between conventional agents (methotrexate, azathioprine, mycophenolate mofetil) 1. This recommendation is based on:
- Proven efficacy in randomized controlled trial: Mepolizumab demonstrated effectiveness specifically in patients with relapsing nonsevere EGPA who were receiving immunosuppressive therapy 1
- Dual mechanism benefit: Mepolizumab independently treats both the underlying EGPA vasculitis and eosinophilic asthma 1
- Superior evidence base: Even for patients with elevated IgE levels, mepolizumab is preferred over omalizumab due to stronger randomized trial evidence 1
Dosing and Administration
Mepolizumab should be administered at 100 mg subcutaneously every 4 weeks for EGPA 2. For severe eosinophilic asthma specifically, the standard dose is also 100 mg subcutaneously every 4 weeks 2.
Prerequisite Optimization
Before escalating systemic immunosuppression, maximize inhaled therapies for asthma control 1. This includes:
- High-dose inhaled corticosteroids
- Long-acting β2-agonists
- Additional inhaled controllers as appropriate 2
This step is critical because inadequate optimization of inhaled therapy may lead to unnecessary systemic immunosuppression escalation 1.
Continuation of Current Therapy
Continue the current conventional immunosuppressant (methotrexate, azathioprine, or mycophenolate mofetil) when adding mepolizumab 1. The guideline specifically frames this as "adding mepolizumab" rather than switching therapy, indicating combination treatment is appropriate 1.
Leukotriene Inhibitor Consideration
If the patient is currently taking a leukotriene inhibitor, continue it 1. Leukotriene inhibitors can help manage asthma and sinonasal disease manifestations, though they should not be used to treat other EGPA manifestations 1. No causal relationship has been established between leukotriene inhibitors and EGPA development 1.
Monitoring for Treatment Response
Assess clinical response objectively after initiating mepolizumab 3. Treatment decisions should be based on documented improvement in:
- Asthma control and exacerbation frequency
- Sinonasal symptom severity
- Glucocorticoid dose reduction capability
- Overall disease activity measures 3
The American Thoracic Society and American Academy of Allergy, Asthma, and Immunology emphasize the importance of documented clinical response for continuation of biologic therapy 3.
Alternative Scenario: If Not on Conventional Immunosuppressant
If this patient were experiencing nonsevere relapse while receiving only low-dose glucocorticoids without other therapy, mepolizumab would still be the preferred addition over starting methotrexate, azathioprine, or mycophenolate mofetil 1. This reflects mepolizumab's proven efficacy in this specific population 1.
Safety Profile
Mepolizumab demonstrates a favorable safety profile with adverse events similar to placebo 2. Common adverse events include:
- Headache
- Injection site reactions
- Back pain
- Nasopharyngitis 2
No significant safety concerns preclude its use in this clinical context 2.
What NOT to Do
Do not switch to omalizumab, even if the patient has elevated serum IgE levels 1. The published evidence on omalizumab in EGPA is limited, and mepolizumab remains the preferred choice based on randomized controlled trial data 1.
Do not discontinue leukotriene inhibitors if the patient is currently taking them, as retrospective studies have not concluded a causal relationship between these medications and EGPA 1.
Do not increase systemic immunosuppression before optimizing inhaled therapies for asthma control 1.