Understanding What Drugs Decrease IgE Levels for Allergic Conditions

October 14, 2025 •

5 min read

Excessive immunoglobulin E (IgE) is a key player in the pathogenesis of numerous severe allergic diseases, including asthma, chronic urticaria, and food allergies. By developing therapies specifically designed to decrease IgE levels, medical science offers new, targeted treatment options for patients whose conditions are not well-controlled by standard medication.

Quick Summary

This article explores the primary anti-IgE medications, focusing on omalizumab and emerging therapies. It details how these drugs function, their approved applications, and distinguishes between free and total IgE levels.

Key Points

Anti-IgE Drugs Neutralize Free IgE: Medications like omalizumab specifically bind to free-floating IgE in the blood, preventing it from initiating allergic reactions.
Omalizumab is Approved for Several Severe Allergies: This medication is widely used for severe allergic asthma, chronic spontaneous urticaria, and nasal polyps in patients who don't respond to standard treatments.
Total IgE May Rise During Omalizumab Therapy: While free IgE is reduced, total IgE measurements may increase because omalizumab-IgE complexes clear from the body slowly.
Newer Biologics Offer Higher Potency: Next-generation drugs like ligelizumab are being developed to bind IgE with higher affinity, potentially offering greater efficacy.
Other Drugs Can Indirectly Lower IgE: High-dose corticosteroids, montelukast, and certain antihistamines may also cause a decrease in IgE as a secondary effect of their anti-inflammatory actions.
Novel Therapies Target IgE Production: Emerging biologics like XmAb7195 and the former quilizumab aimed to reduce IgE production by targeting IgE-producing B cells, offering a different approach to long-term IgE reduction.
Patient Selection is Crucial: Due to the varying mechanisms and costs, anti-IgE therapies are typically reserved for patients with severe IgE-mediated diseases that are inadequately controlled by other medications.

The Role of Immunoglobulin E in Allergic Disease

Immunoglobulin E (IgE) is a class of antibody that plays a central role in Type I hypersensitivity reactions, commonly known as allergies. In predisposed individuals, exposure to an allergen triggers the immune system to produce large quantities of IgE. These IgE antibodies then circulate in the bloodstream before binding to high-affinity IgE receptors (FcεRI) located on the surface of mast cells and basophils.

When the same allergen is encountered again, it cross-links the IgE antibodies on the surface of these cells. This cross-linking activates the cells, triggering a rapid release of inflammatory mediators such as histamine, leukotrienes, and prostaglandins. These mediators cause the classic symptoms of allergic reactions, including wheezing, itching, and nasal congestion. Chronic activation of this pathway contributes to persistent inflammation seen in conditions like severe asthma and chronic hives.

Omalizumab: The Pioneering Anti-IgE Monoclonal Antibody

Omalizumab, marketed as Xolair®, is a recombinant humanized monoclonal antibody and the most well-known anti-IgE drug. It is a biological agent approved for the treatment of specific allergic conditions.

Mechanism of action: Omalizumab works by binding to free-floating IgE in the blood. Crucially, it attaches to the same part of the IgE molecule (the Fc region) that would normally bind to the FcεRI receptors on mast cells and basophils. By sequestering this free IgE, omalizumab prevents it from initiating the allergic cascade. Over time, this also leads to a significant downregulation of the FcεRI receptors on the surface of these inflammatory cells, making them less sensitive to allergens.
Free vs. Total IgE: It is important to note that while omalizumab dramatically reduces levels of free IgE (which triggers allergies), the measurement of total IgE in the blood can paradoxically increase. This is because the IgE-omalizumab complexes clear more slowly from the body, and most lab assays measure both the free IgE and the complexed IgE. Healthcare providers rely on the patient's pre-treatment IgE level and body weight to determine the correct dosage.
Approved Indications: Omalizumab is approved for:
- Moderate to severe persistent allergic asthma in patients 6 years of age and older.
- Chronic spontaneous urticaria (CSU or chronic hives) in adults and adolescents 12 years and older.
- Chronic rhinosinusitis with nasal polyps in adults.
- Certain IgE-mediated food allergies.

Next-Generation Anti-IgE and IgE-Targeting Therapies

Ongoing research has led to the development of newer anti-IgE therapies designed to be more potent or have different mechanisms of action. These include:

Ligelizumab (QGE031): This humanized monoclonal antibody is engineered to bind to IgE with a higher affinity than omalizumab. Clinical trials have shown that ligelizumab can suppress free IgE and basophil activation more effectively, suggesting it may offer better clinical outcomes, especially for omalizumab non-responders.
Quilizumab: Unlike omalizumab which binds to free IgE, quilizumab targets the M1-prime segment of membrane-bound IgE on IgE-producing B cells. The goal is to induce B-cell apoptosis and inhibit the production of IgE at the source. While phase II trials showed promise by reducing total IgE, further development in allergic asthma and chronic urticaria was discontinued due to a lack of significant clinical benefit.
XmAb7195: This monoclonal antibody is designed with a dual mechanism. It captures free IgE similar to omalizumab, but also binds to an inhibitory receptor on B cells (FcγRIIβ) to reduce the number of IgE-secreting plasma cells. This leads to a more pronounced and longer-lasting reduction in total IgE levels.
Immunoadsorption: This medical procedure uses plasmapheresis to physically remove IgE and immune complexes from the bloodstream. It has been used for severe, intractable allergic diseases but is less common than monoclonal antibody therapy.

Other Medications with Indirect Effects on IgE

Beyond the specific anti-IgE biologics, other medication classes can indirectly influence or reduce IgE-related inflammation, though their primary mechanism is not to sequester IgE.

Corticosteroids: Inhaled corticosteroids are a cornerstone of asthma management. By powerfully suppressing inflammation in the airways, they can reduce the inflammatory cascade that drives IgE production. Studies have shown that high-dose inhaled corticosteroids can lead to a decrease in serum IgE levels in children with asthma.
Leukotriene Receptor Antagonists: Drugs like montelukast block the action of leukotrienes, another class of inflammatory mediators. By interrupting this part of the allergic response, they can provide anti-inflammatory effects. Research has shown that montelukast can also decrease serum IgE levels in some atopic asthma patients, possibly by reducing the production of interleukin 4, a cytokine crucial for IgE synthesis.
H1 Antihistamines: Second-generation antihistamines, such as levocetirizine and desloratadine, primarily block histamine receptors but also possess anti-inflammatory properties. Clinical studies have shown that prolonged use can result in a modest, but significant, reduction of total IgE in allergic rhinitis patients by dampening the systemic inflammation.
Dupilumab (Dupixent): While not a direct anti-IgE drug, dupilumab is a monoclonal antibody that targets the interleukin-4 receptor alpha subunit (IL-4Rα). By blocking both IL-4 and IL-13 signaling, it inhibits a key pathway responsible for IgE production. Dupilumab is approved for atopic dermatitis, asthma, and other eosinophilic conditions, and its mechanism effectively reduces allergic inflammation by targeting the IgE production pathway upstream.

Comparison of Anti-IgE Therapies


Feature	Omalizumab (Xolair)	Ligelizumab	Quilizumab	XmAb7195
Mechanism	Binds to free IgE in the bloodstream, preventing it from attaching to receptors on effector cells like mast cells.	Binds to free IgE with higher affinity than omalizumab, offering potentially greater suppression.	Binds to membrane-bound IgE on B cells to reduce IgE production at the source.	Dual mechanism: Binds free IgE and targets an inhibitory receptor on B cells to reduce IgE production.
Drug Type	Humanized Monoclonal Antibody	Humanized Monoclonal Antibody	Humanized Monoclonal Antibody	Monoclonal Antibody
Status	FDA-approved for allergic asthma, CSU, nasal polyps, and certain food allergies.	Phase 2b/III trials; demonstrated superiority to omalizumab in some studies.	Development discontinued in allergic asthma and CSU.	Phase I trial completed.
Effect on IgE	Reduces free IgE but can increase total IgE measurements due to IgE-drug complexes.	Significantly reduces free IgE and FcεRI expression.	Aimed to reduce total IgE by targeting producer B cells.	Reduces both free and total IgE levels by targeting free IgE and producer B cells.

Conclusion

Targeting IgE represents a significant advancement in the treatment of severe allergic diseases, offering hope to patients whose symptoms are inadequately managed by conventional therapies. Omalizumab remains the primary anti-IgE medication, with a proven track record for controlling severe asthma, chronic urticaria, and other allergic conditions by neutralizing free IgE and reducing the sensitivity of inflammatory cells. Its unique effect on total IgE levels, while reducing free IgE, is a key consideration for healthcare providers. The ongoing development of more potent anti-IgE biologics, such as ligelizumab, and innovative therapies like XmAb7195, promises even more effective and targeted options in the future. Furthermore, other standard anti-inflammatory drugs can indirectly contribute to lower IgE levels by dampening the overall allergic response. Selecting the most appropriate treatment requires a thorough assessment by a healthcare professional, considering the specific allergic condition and individual patient profile.

Learn more about anti-IgE therapies from the National Center for Biotechnology Information.

Frequently Asked Questions

The main anti-IgE medication is omalizumab (Xolair®). It is a monoclonal antibody that binds to and neutralizes free IgE in the bloodstream, preventing allergic reactions.

Omalizumab significantly decreases the level of free IgE in the blood almost immediately. However, the measure of total IgE can appear higher after starting treatment because the omalizumab-IgE complexes are cleared more slowly by the body and are detected by laboratory tests.

Omalizumab is approved for treating specific IgE-mediated conditions, including moderate-to-severe persistent allergic asthma, chronic spontaneous urticaria (chronic hives), chronic rhinosinusitis with nasal polyps, and certain food allergies.

Yes, several new anti-IgE therapies are in development. Ligelizumab is an example of a next-generation monoclonal antibody with a higher binding affinity for IgE than omalizumab. Other therapies target the B cells that produce IgE.

Yes. While not their primary function, some anti-inflammatory medications, such as high-dose inhaled corticosteroids and leukotriene modifiers like montelukast, have been shown to cause a reduction in serum IgE levels.

Yes, drugs like dupilumab, which block the IL-4/IL-13 pathway, can effectively reduce IgE levels. The IL-4/IL-13 pathway is an upstream signal for IgE production, so blocking it leads to a reduction in IgE and associated inflammation.

Free serum IgE levels decrease within an hour of omalizumab administration. However, it can take several weeks to months to see the full clinical effect of the medication.