From the Guidelines
Mepolizumab is a recommended treatment for severe asthma with high eosinophil count, as it significantly reduces asthma exacerbations and improves quality of life. The medication works by blocking interleukin-5 (IL-5), a key cytokine for eosinophil maturation, differentiation, and survival 1.
Key Points
- Mepolizumab is administered as a subcutaneous injection, with a recommended dosage of 300 mg every 4 weeks for patients with severe asthma and high eosinophil count 1.
- However, a lower initial dosage of 100 mg every 4 weeks can be considered, particularly in patients with limited respiratory manifestations, and subsequently titrated up to 300 mg every 4 weeks in patients with an unsatisfactory response to treatment 1.
- The medication has been shown to be effective in reducing asthma exacerbations, improving lung function, and allowing glucocorticoid sparing 1.
- Common side effects include headache, injection site reactions, and back pain, but serious adverse events are rare.
- Regular monitoring of eosinophil counts and asthma symptoms is recommended to assess treatment response.
Mechanism of Action
Mepolizumab binds to IL-5, preventing it from attaching to eosinophils, which reduces eosinophil production and survival in the bone marrow and decreases their accumulation in the lungs 1. This mechanism directly addresses the underlying type 2 inflammation pathway that drives eosinophilic asthma.
Patient Selection
Patients with severe asthma and high eosinophil count, typically above 300 cells/μL, despite using high-dose inhaled corticosteroids and other controller medications, are eligible for mepolizumab treatment 1.
Treatment Outcomes
Mepolizumab has been shown to significantly improve quality of life, reduce asthma exacerbations, and decrease oral corticosteroid requirements in patients with severe eosinophilic asthma 1.
From the FDA Drug Label
Mepolizumab is an IL-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in adult subjects with asthma and blood eosinophil levels >200 cells/mcL. Compared with baseline levels, blood eosinophils decreased in a dose-dependent manner. On Day 84 (4 weeks post‑last dose), the observed geometric mean reduction from baseline in blood eosinophils was 64%, 78%, 84%, and 90% in the 12. 5-mg subcutaneous, 75-mg IV, 125-mg subcutaneous, and 250-mg subcutaneous treatment groups, respectively.
The role of Mepolizumab in treating severe asthma with high eosinophil count is to reduce the production and survival of eosinophils by inhibiting IL-5 signaling.
- Key benefits of Mepolizumab include:
- Reduction of blood eosinophil levels in a dose-dependent manner
- Geometric mean reduction from baseline in blood eosinophils of up to 90%
- Maintenance of reduced eosinophil levels throughout the treatment period 2
From the Research
Role of Mepolizumab in Treating Severe Asthma
Mepolizumab, an anti-interleukin-5 antibody, plays a significant role in treating severe asthma with a high eosinophil count. The key aspects of its role are:
- Reduction in Eosinophil Count: Mepolizumab has been shown to reduce the circulating eosinophil count, which is a key factor in the pathogenesis of severe eosinophilic asthma 3, 4.
- Improvement in Lung Function: Studies have demonstrated that mepolizumab improves lung function, as measured by forced expiratory volume (FEV1) 4, 5.
- Reduction in Asthma Exacerbations: Mepolizumab has been found to reduce the rate of asthma exacerbations, which is a critical outcome in the management of severe asthma 4, 5.
- Enhancement of Asthma Control: The use of mepolizumab has been associated with improved asthma control, as measured by the Asthma Control Questionnaire (ACQ) and the Asthma Control Test (ACT) 4, 5.
Comparison with Other Biologics
Mepolizumab has been compared with other biologics, such as benralizumab and dupilumab, in the treatment of severe eosinophilic asthma. The key findings are:
- Similar Efficacy: Mepolizumab, benralizumab, and dupilumab have been found to have similar efficacy in reducing asthma exacerbations and improving lung function 5, 6.
- Minimal Differences in Safety: The safety profiles of mepolizumab, benralizumab, and dupilumab have been found to be similar, with minimal differences in the risk of serious adverse events 5, 6.
Clinical Implications
The use of mepolizumab in the treatment of severe asthma with a high eosinophil count has significant clinical implications:
- Personalized Medicine: Mepolizumab can be used as a targeted therapy for patients with severe eosinophilic asthma, providing a personalized approach to treatment 3, 4.
- Add-on Therapy: Mepolizumab can be used as an add-on therapy to conventional treatments, such as inhaled corticosteroids and long-acting β2 agonists, to improve asthma control and reduce exacerbations 3, 4.