What is the best medicine to reduce eosinophils? A guide to targeted treatments

While corticosteroids were traditionally the standard for controlling eosinophil-related inflammation, the best medicine to reduce eosinophils has evolved dramatically with the advent of targeted biologic therapies. The optimal treatment choice now depends heavily on the specific disease driving the eosinophilia, such as severe asthma, hypereosinophilic syndrome (HES), or eosinophilic esophagitis (EoE).

Quick Summary

This guide explains how the choice of medication to reduce eosinophils is tailored to the underlying condition and severity, discussing corticosteroids and modern targeted biologics that specifically address eosinophilic inflammation. It highlights the mechanisms, primary indications, and different approaches to managing various eosinophilic disorders.

Key Points

• No Single 'Best' Medication: The most effective medicine to reduce eosinophils depends on the specific disease causing the high levels, such as severe asthma, HES, or EoE.

• Corticosteroids for Rapid Control: Systemic corticosteroids like prednisone are highly effective for rapid, short-term reduction of eosinophils but are associated with significant long-term side effects.

• Targeted Biologics for Chronic Conditions: Newer biologic therapies, including mepolizumab, benralizumab, dupilumab, and tezepelumab, offer more specific and safer long-term management for various eosinophilic diseases.

• Targeting IL-5: Mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra) block the IL-5 pathway, a key driver of eosinophil production and survival.

• Targeting IL-4 and IL-13: Dupilumab (Dupixent) blocks signals that contribute to type 2 inflammation and is effective for eosinophilic asthma and EoE.

• Targeting Upstream Signals: Tezepelumab (Tezspire) blocks TSLP, reducing multiple inflammatory pathways and is indicated for severe asthma.

• Specific Therapies for HES: For certain forms of HES, genetic testing determines if a tyrosine kinase inhibitor like imatinib (Gleevec) is the appropriate therapy.

• Specialist Guidance is Crucial: A personalized treatment plan based on a definitive diagnosis from an allergist, immunologist, or hematologist is essential for managing eosinophilia safely and effectively.

Understanding the Role of Eosinophils and Eosinophilic Disorders

Eosinophils are a type of white blood cell involved in the body's immune response, particularly against parasitic infections and in allergic reactions. When present in excessively high numbers, a condition known as eosinophilia or hypereosinophilia, these cells can cause inflammation and damage to various organs throughout the body, including the lungs, heart, gastrointestinal tract, and skin.

Eosinophilic diseases are diverse and include severe eosinophilic asthma (a specific subtype of asthma), hypereosinophilic syndrome (HES), eosinophilic esophagitis (EoE), eosinophilic granulomatosis with polyangiitis (EGPA), and chronic rhinosinusitis with nasal polyps (CRSwNP). For each of these conditions, suppressing the population of eosinophils is a key goal of treatment to prevent tissue damage and control symptoms. The best course of action is determined by a physician based on the specific diagnosis.

Corticosteroids: The Traditional First-Line Treatment

For many years, corticosteroids were the cornerstone of therapy for high eosinophil counts, particularly in cases with significant organ involvement.

• Mechanism of Action: Systemic corticosteroids like prednisone work by inhibiting eosinophil survival and promoting their clearance from the blood and tissues. They are highly effective and can provide rapid relief from inflammatory symptoms associated with eosinophilia.
• Indications: They are often used as the first-line treatment for a rapid response, especially in severe or acute episodes of eosinophilic disease. They can be administered orally or intravenously depending on the clinical situation. In conditions like EoE, swallowed topical corticosteroids (e.g., oral budesonide) are also used to treat localized inflammation.
• Drawbacks: The primary limitation of corticosteroids is the long list of potentially serious side effects associated with long-term use, such as osteoporosis, weight gain, diabetes, and infections. As a result, they are often used for short-term control or at the lowest possible maintenance dose, with the goal of eventually tapering off or switching to a more targeted therapy.

Targeted Biologics: The Modern, Specific Approach

In recent years, the development of biologic medications has revolutionized the treatment of chronic eosinophilic diseases. These therapies are more precise than corticosteroids, targeting specific parts of the immune system that drive eosinophil production and activity.

Anti-Interleukin-5 (Anti-IL-5) Therapies

Interleukin-5 (IL-5) is a key cytokine responsible for the growth, maturation, and survival of eosinophils. Blocking the IL-5 pathway is a highly effective way to reduce eosinophil levels.

• Mepolizumab (Nucala): A monoclonal antibody that binds to IL-5, preventing it from signaling eosinophil production. It is approved for severe eosinophilic asthma, HES, EGPA, and CRSwNP. It is administered via a subcutaneous injection every four weeks.
• Reslizumab (Cinqair): Another monoclonal antibody that binds directly to IL-5. Approved for severe eosinophilic asthma in adults, it is given as an intravenous (IV) infusion every four weeks and is weight-based.
• Benralizumab (Fasenra): This monoclonal antibody binds to the IL-5 receptor on the surface of eosinophils, basophils, and their precursors. This causes rapid and nearly complete depletion of these cells through a process called antibody-dependent cell-mediated cytotoxicity (ADCC). It is approved for severe eosinophilic asthma and EGPA and is given by injection every eight weeks after an initial loading period.

Anti-Interleukin-4 and Interleukin-13 (Anti-IL-4/IL-13) Therapy

• Dupilumab (Dupixent): This biologic targets the shared receptor component for both IL-4 and IL-13, two cytokines that contribute to the type 2 inflammation associated with eosinophilic diseases. It is approved for eosinophilic asthma and EoE, among other conditions, and is administered via injection every two weeks.

Anti-Thymic Stromal Lymphopoietin (Anti-TSLP) Therapy

• Tezepelumab-ekko (Tezspire): A biologic that blocks thymic stromal lymphopoietin (TSLP), an upstream cytokine involved in the inflammatory cascade. By blocking TSLP, it inhibits the release of downstream cytokines like IL-4, IL-5, and IL-13, thereby reducing eosinophil levels and inflammation. It is approved for severe asthma.

Other Medications for Specific Conditions

For certain hypereosinophilic syndromes, other medications may be necessary, especially those associated with specific genetic mutations.

• Imatinib (Gleevec): A tyrosine kinase inhibitor that is the first-line treatment for a specific type of HES driven by the FIP1L1-PDGFRA fusion gene. Genetic testing is crucial to determine if a patient will respond to this medication.
• Hydroxyurea: A cytotoxic agent used in some cases of HES, particularly for patients who don't respond to corticosteroids or imatinib.

A Comparative Look at Eosinophil-Reducing Medications

Medication (Brand Name)	Mechanism of Action	Primary Indications	Administration	Special Considerations
Corticosteroids (e.g., Prednisone)	Suppress inflammation broadly, induce eosinophil apoptosis and inhibit production	Acute flares, first-line for many HES cases, EoE (topical)	Oral, IV, or Swallowed Topical	Significant long-term side effects; used for short-term control or low-dose maintenance.
Mepolizumab (Nucala)	Binds to Interleukin-5 (IL-5) to block signaling	Severe Eosinophilic Asthma, HES, EGPA, CRSwNP	Subcutaneous injection every 4 weeks	Steroid-sparing effect; safe for long-term use.
Reslizumab (Cinqair)	Binds to Interleukin-5 (IL-5) to block signaling	Severe Eosinophilic Asthma (adults)	Intravenous infusion every 4 weeks	Weight-based dosing; requires healthcare professional administration.
Benralizumab (Fasenra)	Binds to IL-5 receptor, triggering cell death	Severe Eosinophilic Asthma, EGPA	Subcutaneous injection every 8 weeks (after initial doses)	Causes more complete depletion of eosinophils and precursors.
Dupilumab (Dupixent)	Blocks IL-4 and IL-13 signaling	Severe Eosinophilic Asthma, Eosinophilic Esophagitis (EoE)	Subcutaneous injection every 1 or 2 weeks	Approved for a wide range of T2 inflammatory diseases.
Tezepelumab (Tezspire)	Blocks Thymic Stromal Lymphopoietin (TSLP) upstream	Severe Asthma	Subcutaneous injection every 4 weeks	Reduces multiple inflammatory markers.
Imatinib (Gleevec)	Tyrosine Kinase Inhibitor	FIP1L1-PDGFRA positive HES	Oral tablet	Effective only for specific genetic mutations; requires testing.

The Need for a Personalized Approach

There is no single "best" medication to reduce eosinophils for all patients. The most effective treatment is one that is specifically chosen based on a thorough medical evaluation that identifies the underlying cause and severity of the eosinophilia.

For conditions like severe asthma, a biologic such as mepolizumab, benralizumab, or dupilumab may be the ideal long-term solution for patients who are not well-controlled on inhaled steroids. For hypereosinophilic syndrome (HES), the treatment strategy is guided by genetic testing, with imatinib being the best option for those with the FIP1L1-PDGFRA mutation, while biologics or other agents are used for other subtypes. For eosinophilic esophagitis (EoE), dupilumab has become the first specifically approved biologic, offering significant improvement in both symptoms and histological inflammation.

Conclusion

While systemic corticosteroids remain a powerful tool for rapidly reducing eosinophil counts in severe situations, they are not the ideal long-term solution due to their side effect profile. The field of eosinophilic disease management has moved towards a more precise, personalized approach with the use of targeted biologic therapies. For patients with specific chronic eosinophilic conditions, these newer medications offer more effective, long-term control with fewer systemic side effects, significantly improving quality of life. A detailed diagnosis by a specialist is the essential first step to determine the best medication to reduce eosinophils for your unique health situation.

For more detailed information on specific conditions, consult the American Partnership for Eosinophilic Disorders: https://apfed.org/.

Frequently Asked Questions

What is the fastest way to reduce high eosinophil counts?

The fastest way to reduce high eosinophil counts is often with a course of systemic corticosteroids like prednisone, which can quickly suppress the immune response and promote eosinophil clearance. However, this is typically a short-term solution for acute situations due to the risk of side effects with long-term use.

Are biologic drugs more effective than corticosteroids for reducing eosinophils?

Biologic drugs are often considered a safer and more specific long-term treatment than corticosteroids, especially for chronic eosinophilic conditions. They target the root cause of the eosinophil overproduction, offering effective and sustained control with fewer systemic side effects, allowing patients to reduce or eliminate their reliance on oral steroids.

How do I know which biologic medication is right for my condition?

The right biologic depends on your specific diagnosis. For instance, mepolizumab, benralizumab, and reslizumab target the IL-5 pathway, while dupilumab targets the IL-4/IL-13 pathway. A specialist, such as an allergist or immunologist, will determine the most appropriate biologic based on your medical history, type of eosinophilic disease, and its severity.

Can diet help reduce eosinophils instead of medicine?

While elimination diets are a primary treatment for some eosinophilic diseases like eosinophilic esophagitis (EoE), they are typically not a substitute for medication, especially in severe or systemic conditions. Diet can play a significant role, but the most effective treatment approach should be discussed with a healthcare provider and may involve a combination of dietary changes and medication.

What are the long-term side effects of taking medications to reduce eosinophils?

Long-term use of systemic corticosteroids can lead to serious side effects like osteoporosis, weight gain, and diabetes. Targeted biologic therapies generally have a more favorable side effect profile, though potential risks can include injection-site reactions, hypersensitivity reactions, and increased risk of infections.

Is eosinophilia always treated with medication?

No. Not all cases of eosinophilia require medication. The decision to treat depends on the underlying cause, the severity of the eosinophil count, and whether there is evidence of organ damage. In cases of hypereosinophilia of unknown significance with no organ involvement, doctors may choose to monitor the condition closely without immediate treatment.

What is the difference between mepolizumab and benralizumab?

Both mepolizumab (Nucala) and benralizumab (Fasenra) target the IL-5 pathway. Mepolizumab binds directly to the IL-5 protein, preventing it from activating eosinophils. In contrast, benralizumab binds to the IL-5 receptor on the eosinophil surface, triggering the cell's destruction through antibody-dependent cell-mediated cytotoxicity (ADCC). This typically leads to a more profound and sustained depletion of eosinophils with benralizumab.