Summary

Mepolizumab and benralizumab are both anti-IL-5 monoclonal antibodies used to treat severe eosinophilic asthma. While they target the same pathway, concurrent use is generally not recommended due to overlapping mechanisms and lack of established safety data for combination therapy.

Introduction

Mepolizumab (Nucala) is a humanized monoclonal antibody that targets interleukin-5 (IL-5), primarily used as add-on maintenance treatment for severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome. Benralizumab (Fasenra) is a humanized monoclonal antibody that targets the IL-5 receptor alpha subunit, indicated for add-on maintenance treatment of severe eosinophilic asthma. Both medications belong to the class of anti-IL-5 biologics and work by reducing eosinophil levels and activity in the respiratory system.

Mechanism of Interaction

Both mepolizumab and benralizumab target the IL-5 pathway but through different mechanisms. Mepolizumab directly binds to IL-5, preventing it from binding to its receptor on eosinophils and basophils. Benralizumab binds to the IL-5 receptor alpha subunit on eosinophils and basophils, blocking IL-5 signaling and inducing antibody-dependent cell-mediated cytotoxicity (ADCC) leading to rapid eosinophil depletion. The overlapping pathway targeting could potentially lead to excessive immunosuppression or unpredictable pharmacodynamic effects when used concurrently.

Risks and Symptoms

The primary concern with concurrent use of mepolizumab and benralizumab is the potential for excessive suppression of the IL-5 pathway, which could lead to increased risk of infections, particularly parasitic infections where eosinophils play a protective role. There is insufficient clinical data on the safety and efficacy of combining these two anti-IL-5 biologics. Additional risks may include increased immunogenicity, unpredictable drug interactions, and potential for severe adverse reactions. The lack of established dosing guidelines for combination therapy also presents clinical management challenges.

Management and Precautions

Concurrent use of mepolizumab and benralizumab is generally not recommended and should be avoided. If a patient requires switching from one anti-IL-5 biologic to another, appropriate washout periods should be considered based on the half-life of each medication (mepolizumab: ~16-22 days, benralizumab: ~15 days). Healthcare providers should monitor for signs of infection, particularly parasitic infections, and assess eosinophil counts regularly. Any decision to use these medications in close temporal proximity should involve careful risk-benefit assessment and close monitoring by a specialist familiar with biologic therapies. Patients should be counseled about potential risks and advised to report any signs of infection or unusual symptoms promptly.