What is Traditional Immunotherapy?
To understand how benralizumab works, it is important to first define conventional immunotherapy. This traditional approach, often called allergy shots or subcutaneous immunotherapy, is used to treat allergic asthma and other allergies. It involves administering a series of injections containing small, increasing doses of specific allergens, like pollen, dust mites, or pet dander, to which a person is allergic. The goal is to train the immune system to become less reactive to these triggers over time, a process known as desensitization. This therapy is a long-term commitment, often lasting 3 to 5 years, and targets the underlying allergic response, primarily involving IgE antibodies.
The Role of Biologics in Asthma Treatment
For patients with severe asthma that is not well-controlled by traditional inhalers and therapies, a newer class of medications called biologics may be prescribed. These medicines, derived from living organisms, are designed to target and block specific molecules and cells that cause inflammation. There are several FDA-approved biologics for severe asthma, including omalizumab (for allergic asthma) and several that target the interleukin-5 (IL-5) pathway for eosinophilic asthma. Benralizumab falls into this latter category.
Benralizumab: A Targeted Monoclonal Antibody
Benralizumab (brand name Fasenra) is a biologic medication classified as a monoclonal antibody. A monoclonal antibody is a laboratory-produced protein designed to mimic the body’s immune system to attack specific targets. In the case of benralizumab, the target is the alpha subunit of the interleukin-5 receptor (IL-5Rα). This receptor is found on the surface of immune cells, including eosinophils, which are a type of white blood cell involved in inflammation.
By binding to the IL-5Rα receptor, benralizumab works in a unique way to deplete eosinophils. Unlike other biologics that might only block IL-5, benralizumab is an afucosylated antibody. This structural modification enhances its ability to trigger a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). In ADCC, natural killer (NK) cells from the immune system recognize and bind to the benralizumab-coated eosinophils, leading to the rapid and near-complete destruction of these inflammatory cells. This includes not only circulating eosinophils but also resident eosinophils in tissues and precursors in the bone marrow.
Immunomodulation vs. Immunotherapy
While benralizumab and traditional allergen immunotherapy both interact with the immune system, their mechanisms, targets, and goals are fundamentally different.
- Immunomodulation is the process of modifying or regulating an immune response. Benralizumab accomplishes this by selectively and rapidly removing a specific type of inflammatory cell (eosinophils). This targeted modulation reduces the inflammatory cascade driven by eosinophils, thereby alleviating symptoms of severe eosinophilic asthma and EGPA.
- Allergen Immunotherapy, on the other hand, aims to desensitize the immune system to external allergens. It changes the overall immune response to a specific trigger over a prolonged period by shifting the production of certain antibodies.
This distinction is crucial. Benralizumab does not desensitize the body to an allergen; instead, it directly intervenes in the inflammatory process by targeting the cells responsible for it in eosinophilic disease. The therapeutic benefit comes from stopping the inflammatory attack in its tracks, not from retraining the immune system to ignore a specific trigger.
Benralizumab vs. Traditional Allergen Immunotherapy
| Feature | Benralizumab (Fasenra) | Traditional Allergen Immunotherapy (Allergy Shots) |
|---|---|---|
| Mechanism | Monoclonal antibody binds to IL-5Rα and triggers cell death (ADCC) of eosinophils. | Introduces increasing doses of allergens to desensitize the immune system. |
| Target | The IL-5Rα receptor on eosinophils and basophils, leading to their depletion. | The immune system's response to specific allergens, primarily via IgE antibodies. |
| Treatment For | Severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). | Allergic asthma and other allergies to specific triggers. |
| Administration | Subcutaneous injection, initially every 4 weeks, then every 8 weeks. | Series of subcutaneous injections, typically starting weekly and extending to monthly over years. |
| Onset of Effect | Rapid reduction of eosinophils within 24 hours, with clinical improvement seen within weeks. | Gradual, with noticeable improvement developing over several months. |
Clinical Benefits and Considerations
Clinical trials have demonstrated significant benefits for patients with severe eosinophilic asthma treated with benralizumab. Key findings include:
- Reduced Exacerbations: Benralizumab has been shown to significantly reduce the rate of asthma attacks in patients with elevated blood eosinophil counts.
- Improved Lung Function: Patients have experienced improvements in lung function, as measured by forced expiratory volume in one second (FEV1).
- Oral Steroid Reduction: The medication can help reduce or even eliminate the need for oral corticosteroids in dependent patients, minimizing the risk of long-term side effects.
It is important to note that benralizumab is not a rescue medication for acute asthma attacks and should be continued alongside other prescribed asthma treatments. Before starting therapy, a physician will assess a patient’s eosinophil count and other clinical factors to determine if benralizumab is the appropriate treatment.
Conclusion
In conclusion, while benralizumab is not a conventional allergen immunotherapy, it is a highly effective and specific form of immunomodulation. As a targeted biologic, it directly addresses the underlying eosinophilic inflammation in certain types of severe asthma and EGPA by depleting the responsible cells. Its mechanism, which involves a monoclonal antibody triggering ADCC, is fundamentally different from the desensitization process of traditional allergy shots. For the right patient, it offers a powerful and precise tool to manage their condition, reduce exacerbations, and improve quality of life.
To learn more about the mechanism of benralizumab and other biologics for severe asthma, you can visit the Asthma and Allergy Foundation of America website.
Benralizumab: A targeted immunomodulator
Benralizumab is not a traditional immunotherapy, but a targeted biologic that modulates the immune system.
Blocks IL-5 receptor
It works by binding to the alpha subunit of the interleukin-5 receptor (IL-5Rα) on the surface of eosinophils.
Causes eosinophil depletion
This action triggers antibody-dependent cell-mediated cytotoxicity (ADCC), causing rapid and near-complete elimination of eosinophils.
Used for severe asthma
It is approved as an add-on maintenance treatment for severe eosinophilic asthma.
Not for allergic desensitization
Unlike allergy shots, it does not desensitize the body to specific allergens.
Administered via injection
Benralizumab is given as a subcutaneous injection, either in a clinic or self-administered at home.
Reduces exacerbations and oral steroid use
Clinical trials have shown it can reduce asthma attacks and decrease the need for oral corticosteroids.
