Mepolizumab
Introduction to Mepolizumab
Mepolizumab is a humanized monoclonal antibody that targets interleukin-5 (IL-5), a key cytokine involved in the pathogenesis of eosinophilic inflammation. It was first approved by the FDA in 2015 for the treatment of severe eosinophilic asthma in patients aged 12 years and older. Since then, its indications have expanded to include other eosinophilic disorders.
Mechanism of Action
Mepolizumab works by binding to IL-5 with high affinity and specificity. This binding prevents IL-5 from interacting with its receptor on the surface of eosinophils. Consequently, it inhibits:
- Eosinophil production in the bone marrow
- Eosinophil maturation
- Eosinophil activation and survival
- Eosinophil recruitment to sites of inflammation
By reducing eosinophil levels in blood and tissues, mepolizumab helps control eosinophil-mediated inflammation, which is a key feature of several allergic and inflammatory conditions.
Indications
Mepolizumab is FDA-approved for the following indications:
- Severe eosinophilic asthma in patients aged 6 years and older
- Eosinophilic granulomatosis with polyangiitis (EGPA) in adult patients
- Hypereosinophilic syndrome (HES) in patients aged 12 years and older
- Chronic rhinosinusitis with nasal polyps (CRSwNP) as an add-on maintenance treatment in adult patients
In pediatric patients, the primary focus is on severe eosinophilic asthma, where mepolizumab serves as an add-on maintenance treatment for patients with an eosinophilic phenotype.
Dosage and Administration
The dosage of mepolizumab varies depending on the indication and age of the patient:
- Severe eosinophilic asthma:
- Adults and adolescents (12 years and older): 100 mg subcutaneously every 4 weeks
- Children (6-11 years): 40 mg subcutaneously every 4 weeks
- EGPA: 300 mg subcutaneously every 4 weeks (adults only)
- HES: 300 mg subcutaneously every 4 weeks (12 years and older)
- CRSwNP: 100 mg subcutaneously every 4 weeks (adults only)
Mepolizumab is administered as a subcutaneous injection, typically in the upper arm, thigh, or abdomen. It's important to rotate injection sites to prevent lipohypertrophy.
Efficacy
Clinical trials have demonstrated the efficacy of mepolizumab in its approved indications:
- Severe eosinophilic asthma: Mepolizumab significantly reduces exacerbation rates, improves lung function, and allows for reduction in oral corticosteroid use. In pediatric patients (6-11 years), it showed a 59% reduction in the annual rate of clinically significant exacerbations.
- EGPA: Mepolizumab increased the likelihood of remission and reduced relapse rates compared to placebo.
- HES: Treatment with mepolizumab resulted in significantly fewer HES flares and a higher proportion of patients with improved symptoms.
- CRSwNP: Mepolizumab demonstrated improvements in nasal polyp size, nasal obstruction, and need for surgery.
Safety Profile
Mepolizumab is generally well-tolerated, with a favorable safety profile. Common adverse events include:
- Headache
- Injection site reactions
- Back pain
- Fatigue
- Influenza
- Urinary tract infection
Rare but serious adverse events may include:
- Hypersensitivity reactions, including anaphylaxis
- Herpes zoster infections
- Opportunistic infections
Long-term safety data in pediatric patients are still being collected, but current evidence suggests a similar safety profile to adults.
Pediatric Considerations
When using mepolizumab in pediatric patients, consider the following:
- Age-appropriate dosing: Ensure correct dosing based on age and indication.
- Asthma control: Mepolizumab is not for acute bronchospasm or status asthmaticus. Patients should have appropriate rescue medications available.
- Parasitic infections: Treat pre-existing helminth infections before initiating mepolizumab. If a patient becomes infected while on treatment, temporarily discontinue mepolizumab.
- Vaccination: Live vaccines should not be given concurrently with mepolizumab. Ensure patients are up-to-date with vaccinations before starting treatment.
- Growth and development: Monitor growth and pubertal development in long-term use, as effects are not yet fully characterized.
- Patient education: Instruct patients and caregivers on proper subcutaneous injection technique if self-administering.
