Summary

Reslizumab and benralizumab are both IL-5 pathway inhibitors used to treat severe eosinophilic asthma. While no direct pharmacokinetic interactions are expected between these monoclonal antibodies, concurrent use is generally not recommended due to overlapping mechanisms of action and lack of established safety data for combination therapy.

Introduction

Reslizumab (Cinqair) is a humanized monoclonal antibody that directly binds to interleukin-5 (IL-5), preventing its interaction with IL-5 receptors on eosinophils. It is indicated as add-on maintenance treatment for severe asthma with an eosinophilic phenotype in patients 18 years and older. Benralizumab (Fasenra) is a humanized monoclonal antibody that binds to the alpha subunit of the IL-5 receptor on eosinophils and basophils, leading to direct cell depletion through antibody-dependent cell-mediated cytotoxicity (ADCC). It is also indicated for severe eosinophilic asthma as add-on maintenance therapy in patients 12 years and older.

Mechanism of Interaction

Both reslizumab and benralizumab target the IL-5 pathway but through different mechanisms. Reslizumab neutralizes circulating IL-5, preventing it from binding to its receptor, while benralizumab directly binds to the IL-5 receptor alpha subunit and induces eosinophil apoptosis through ADCC. Since both drugs are large protein molecules (monoclonal antibodies), they are unlikely to have direct pharmacokinetic interactions through cytochrome P450 enzymes or drug transporters. However, their overlapping pharmacodynamic effects on eosinophil reduction could potentially lead to additive immunosuppressive effects.

Risks and Symptoms

The primary concern with concurrent use of reslizumab and benralizumab is the potential for excessive eosinophil depletion and increased immunosuppression. While eosinophil reduction is the therapeutic goal, profound depletion may increase susceptibility to parasitic infections and potentially affect immune surveillance. Additionally, both medications carry risks of hypersensitivity reactions, including anaphylaxis, and the combination may theoretically increase this risk. There is insufficient clinical data to establish the safety profile of concurrent use, making risk assessment challenging.

Management and Precautions

Concurrent use of reslizumab and benralizumab is generally not recommended due to overlapping mechanisms and lack of safety data. If switching between these agents is necessary, healthcare providers should consider appropriate washout periods based on each drug's half-life and duration of action. Reslizumab has a half-life of approximately 24 days, while benralizumab has a half-life of about 15 days. Monitor patients closely for signs of infection, hypersensitivity reactions, and changes in eosinophil counts. Any decision to use these agents in combination should involve careful risk-benefit assessment and close monitoring by specialists experienced in biologic therapy for severe asthma.