The Impact of Omalizumab in Allergic Disease – A Review of Therapeutic Benefits

Abstract

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases, including asthma, rhinitis, food allergy, and anaphylaxis. The discovery of IgE led to the development of omalizumab, a recombinant humanized monoclonal antibody that selectively binds circulating IgE, thereby preventing its interaction with high-affinity Fc?RI receptors on mast cells and basophils. This reduces the release of inflammatory mediators, downregulates Fc?RI expression, and attenuates allergic inflammation. Omalizumab has demonstrated proven efficacy as an add-on therapy for moderate-to-severe allergic asthma, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps, improving symptom control, reducing exacerbations, and enhancing quality of life. Emerging applications include IgE-mediated food allergy, atopic dermatitis, and other allergic or autoimmune conditions. While generally well-tolerated, rare adverse effects such as anaphylaxis and potential cardiovascular events require monitoring. Despite its cost, omalizumab’s clinical benefits and reduction in healthcare utilization underscore its importance as a targeted biologic in IgE-driven diseases.

Keywords

Introduction

In 1921, Prausnitz and Küstner showed that allergic reactions could be transferred via serum, suggesting a bloodborne factor later identified as IgE in the 1960s by Ishizaka, Johansson, and Bennich. IgE was soon linked to asthma, rhinitis, food allergy, and anaphylaxis. Landmark studies confirmed that total and specific IgE levels correlate with asthma prevalence, bronchial hyperresponsiveness, and persistent sensitization. Traditional therapies targeted downstream mediators, while molecular approaches sought to block central pathways. Among these, omalizumab, an anti-IgE monoclonal antibody, proved successful, becoming the first approved biotherapeutic for asthma and confirming IgE’s central role in allergic disease. Omalizumab is a recombinant DNA-derived humanized Monoclonal antibody that selectively binds human immunoglobulin E (IgE). The antibody is an immunoglobulin (Ig) G1 k with a human framework and complementarity determining regions (CDRs) from a Humanized anti-IgE murine antibody, has revolutionized the management of several allergic and mast cell-driven diseases by selectively targeting and inhibiting immunoglobulin E (IgE). Approved for various indications, its mechanism of action involves binding to free IgE in the bloodstream, thereby preventing IgE from attaching to its high-affinity receptors (FcεRI) on mast cells and basophils. This ultimately reduces the release of inflammatory mediators responsible for allergic responses. This review synthesizes current understanding of omalizumab's efficacy, safety, and emerging applications, drawing from recent literature.

IgE receptors and its function

IgE is a 190 kDa antibody with two heavy and two light chains forming Fab and Fc fragments. The Cε3 domain binds FcεRI receptors on mast cells and basophils, leading to degranulation and allergic reactions. FcεRI is also expressed on eosinophils, monocytes, and dendritic cells, where IgE binding enhances allergen presentation and immune activation. Mast cells and basophils pre-bound with IgE rapidly react when allergens cross-link IgE/FcεRI, causing degranulation and mediator release. Later, cytokines recruit inflammatory cells. IgE also binds FcεRI on dendritic cells for allergen presentation to TH2 cells. CD23 regulates IgE synthesis, facilitates allergen presentation, and mediates IgE/allergen transport, amplifying allergic responses and making IgE a therapeutic target.

Mechanism of Action of Anti IgE or Omalizumab

Omalizumab is a humanized monoclonal antibody that specifically targets circulating free immunoglobulin E (IgE). By binding to free IgE with greater affinity than IgE binds to high-affinity FcεRI receptors on basophils, omalizumab effectively reduces the availability of IgE for receptor binding. Importantly, it does not interact with IgE already bound to FcεRI nor with the receptors themselves, thereby preventing basophil degranulation or inappropriate immune activation. A key downstream effect of this mechanism is FcεRI downregulation. The density of FcεRI on basophils is directly related to the concentration of circulating IgE. As omalizumab lowers serum IgE levels, IgE gradually dissociates from the receptors, leading to decreased FcεRI expression and reduced cellular sensitivity to allergens. This contributes to long-term suppression of allergic responses. In addition, evidence suggests that omalizumab may provide benefits in chronic autoimmune urticaria (CAU). In these patients, reduced FcεRI expression appears to limit IgG autoantibody-mediated cross-linking of adjacent FcεRI α-subunits, thereby preventing inappropriate basophil activation. Through these combined pharmacological actions, omalizumab effectively modulates IgE-mediated pathways, supporting its clinical role in the management of allergic asthma, chronic spontaneous urticaria, and other IgE-driven conditions. Pharmacokinetic studies show omalizumab is absorbed slowly after subcutaneous administration, reaching peak serum concentrations in 7-8 days, with a half-life of approximately 26 days.

Established Indications and Clinical Efficacy

Allergic Asthma: Omalizumab is a well-established add-on therapy for patients aged 6 years and older with moderate-to-severe persistent allergic asthma inadequately controlled by inhaled corticosteroids. Omalizumab targets the Cε3 domain of IgE, blocking its binding to high- and low-affinity receptors. Administered subcutaneously every 2–4 weeks, it rapidly reduces circulating IgE, thereby suppressing allergen-induced bronchoconstriction, airway hyperresponsiveness, and inflammation. The immune complexes formed are safely cleared without activating complement. Clinical trials and real-world studies show that omalizumab decreases asthma exacerbations, lowers corticosteroid dependence, and improves lung function, symptom control, and quality of life, making it a valuable option for severe allergic asthma. A randomized study investigated omalizumab in 45 patients with mild to moderate asthma and sputum eosinophilia ≥2%. Patients received omalizumab (n=22) or placebo (n=23) for 16 weeks. Omalizumab significantly reduced serum IgE and IgE-positive airway mucosal cells. The mean sputum eosinophil count decreased from 6.6% to 1.7% (p<0.001), a much greater reduction than with placebo (8.5% to 7.0%, p<0.05). Tissue analysis revealed marked decreases in eosinophils, FcεRI-positive cells, CD3, CD4, and CD8 T lymphocytes, B cells, and IL-4-positive cells. These findings confirm omalizumab’s strong anti-inflammatory effects. However, airway hyperresponsiveness to methacholine did not improve, indicating IgE and eosinophils may not directly mediate bronchial reactivity in mild to moderate asthma. Overall, the study demonstrates omalizumab’s potential in reducing airway inflammation and clarifies mechanisms by which it reduces exacerbations in more severe asthma, despite limited impact on airway responsiveness.

Chronic Spontaneous Urticaria (CSU): For adults and adolescents (12 years and older) with CSU refractory to H1-antihistamines, omalizumab offers substantial relief from itch and hives. It is the first FDA-approved biologic for CSU, providing a novel therapeutic avenue for patients with this debilitating condition. A study from Denmark by Uysal et al. (2013) introduced an algorithm for using omalizumab in chronic urticaria (CU), differing from its use in asthma where dosing depends on serum IgE and body weight. Twenty-seven patients (6 children, 21 adults) with difficult-to-treat CU and baseline Urticaria Activity Scores (UAS) ≥ 6 were included. All received omalizumab 150 mg subcutaneously every two weeks along with high-dose antihistamines. UAS was assessed regularly, and when scores dropped below 2, the dosing interval was gradually extended up to eight weeks. If symptoms persisted or worsened, dosing intervals were shortened, or the dose was increased to 300 mg. Outcomes showed that 15 patients (55.5%) achieved UAS < 2 with 150 mg; among them, 12 maintained longer dosing intervals, and 3 discontinued omalizumab without relapse. Eight patients (29.6%) required escalation to 300 mg, while 4 (14.8%) were classified as non-responders. Overall, the algorithm was cost-effective, efficient, and well-tolerated, with no major safety concerns. In another trial of 12 patients with chronic autoimmune urticaria (CAU), omalizumab significantly reduced UAS, improved quality of life, and decreased rescue medication use. Seven patients achieved complete remission, and no adverse effects occurred. These findings highlight omalizumab as a safe and effective option for CU and CAU. A Korean study on 26 refractory CU patients found 73.1% responded to omalizumab over 24 weeks. Side effects were mild, and remission was more common in those with allergic disease history. An Indian case series of 5 treatment-resistant CSU patients showed significant improvement with omalizumab. Two achieved complete remission, three required only antihistamines, and mild side effects included headache and fatigue.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Omalizumab is indicated for adults (18 years and older) with CRSwNP whose symptoms are not adequately controlled with nasal corticosteroids. It has shown to reduce polyp size, improve nasal patency, and alleviate CRSwNP-related symptoms. A study from N. Lombardo, C. Pelaia, M. Ciriolo, et al., In a cohort study involving 13 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the efficacy of omalizumab was assessed using four clinical variables: Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Nasal Congestion Score (NCS), and Numeric Rating Scale (NRS). The results were highly encouraging, showing significant improvement across all parameters. Patients reported marked relief from nasal congestion, rhinorrhea, itching, and facial or sinus pressure. Importantly, omalizumab treatment also reduced the need for systemic corticosteroid therapy, thereby lowering steroid-related risks. Additionally, it demonstrated a positive effect in reducing nasal polyp size, contributing to overall symptom control and improved quality of life.

Emerging Indications and Future Directions

Food Allergy: A significant advancement has been the FDA approval of omalizumab for the reduction of allergic reactions, including anaphylaxis, that may occur with accidental exposure to one or more foods in adult and pediatric patients (1 year and older) with IgE-mediated food allergy. This therapy is to be used in conjunction with food allergen avoidance and represents a crucial step forward in managing severe food allergies. Studies have shown it can increase the threshold of tolerated allergen, offering a protective effect.

Atopic dermatitis: Since many patients with atopic dermatitis (AD) show high IgE levels, omalizumab has been explored as a treatment option. Results remain mixed: Lane et al. reported significant improvement in three patients, Vigo et al. observed benefit in five of seven, whereas Krathen and Hsu noted poor responses in three severe cases. These inconsistent outcomes highlight the need for larger, controlled studies before omalizumab can be recommended for AD. At present, its role in managing AD remains uncertain, though it may help selected patients with IgE-driven disease.

Other Allergic Conditions: Investigations are ongoing into its utility in other severe allergic conditions, such as allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis, where IgE plays a significant role in disease pathogenesis.

Safety Profile and Adverse Effects

Omalizumab is generally well-tolerated. Common side effects include injection site reactions, headache, and nasopharyngitis. Serious adverse events, though rare, can occur and include:

Anaphylaxis: While rare, anaphylaxis has been reported after omalizumab administration. Patients should be monitored for a period after injection, especially after the initial doses.

Malignancy: A slight numerical imbalance in malignancies has been observed in some studies, though a causal link has not been definitively established. Ongoing surveillance is crucial.

Cardiovascular and Cerebrovascular Events: Some post-marketing reports have indicated a potential association with cardiovascular and cerebrovascular events, but definitive causality remains under investigation.

Cost-Effectiveness and Real-World Impact

The cost of omalizumab is a significant consideration. While it can be expensive, particularly in the long term, its ability to reduce exacerbations, hospitalizations, and the need for oral corticosteroids can lead to overall healthcare cost savings and improved quality of life for patients with severe, uncontrolled disease. Real-world studies have largely mirrored the efficacy and safety observed in clinical trials, further solidifying its role in clinical practice.

CONCLUSION

 Omalizumab has redefined the management of IgE-mediated diseases by selectively binding circulating IgE, preventing FcεRI receptor activation, and reducing allergic inflammation. It has demonstrated robust efficacy and safety in moderate-to-severe allergic asthma, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps, improving symptom control, reducing exacerbations, and enhancing quality of life. Future research should aim to expand its use to food allergy, atopic dermatitis, and other IgE-driven conditions. Identifying predictive biomarkers and patient characteristics can optimize treatment selection and personalize therapy. Investigating combination approaches with other biologics or immunomodulators may enhance outcomes in refractory cases. Long-term safety surveillance and cost-effectiveness analyses will remain essential to ensure optimal clinical use. Overall, omalizumab exemplifies a precision medicine approach in allergy and immunology, and ongoing studies will further refine its indications, optimize dosing strategies, and improve outcomes for patients with complex IgE-mediated disorders.

REFERENCES

1. U.S. Food and Drug Administration. Omalizumab (Xolair®) prescribing information. Availableat:http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103291.htm
2. Féxil R, Negro JM, Miralles JC. Omalizumab. A review of the New Treatment of Allergic Asthma and Seasonal Allergic Rhinitis. Allergol et Immunopathol 2002; 30(2): 94-9.
3. Foti Randazzese S, Lugarà C, Galletta F, et al. Efficacy of omalizumab after discontinuation: a retrospective single-center observational study in children with severe asthma. Front Allergy. 2025;6:1529624. doi: 10.3389/falgy.2025.1529624
4.  Vieira T, Oliveira J, Castel-Branco M. Short and long-term quality of life and asthma control with omalizumab therapy in a real life setting in Portugal. Allergol Immunopathol 2014; 42: 3–10.
5. Chronic Spontaneous Urticaria | XOLAIR® (omalizumab) | HCP. (Accessed on July 27, 2025).
6. Omalizumab—A Review. PMC. Published 2015.
7. Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) Treatment | XOLAIR® (omalizumab). (Accessed on July 27, 2025).
8. NIH News Release: Omalizumab treats multi-food allergy better than oral immunotherapy. Published 2025.
9. Xolair® (omalizumab) - Information for Healthcare Providers - Genentech. (Accessed on July 27, 2025).
10. Cost-effectiveness of omalizumab in adults with severe asthma: Results from the Asthma Policy Model. PMC. Published 2012.
11. Vichyanond P. 2011. Omalizumab in allergic diseases, a recent review. Asian Pac. J. Allergy Immunol. 29:3209–19
12. Okayama, Y. et al. Roles of omalizumab in various allergic diseases. Allergol. Int. 69, 167–177 (2020).
13.  C.H. Lin, S.L. Cheng A review of omalizumab for the management of severe asthma Drug Des Devel Ther, 10 (2016), pp. 2369-2378
14. Humbert M, Beasley R, Ayres J, Slavin R, Hébert J, Bousquet J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005;60:309–316.
15. Hayashi N, Tsukamoto Y, Sallas WM, et al. A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab. Br J Clin Pharmacol 2007; 63: 548–61
16. Holgate ST, Chuchalin AG, Hébert J, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004; 34: 632–638.
17. Soler, M. et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur. Respir. J. 18, 254–261 (2001).
18. N. Lombardo, C. Pelaia, M. Ciriolo, et al., “Real-Life Effects of Benralizumab on Allergic Chronic Rhinosinusitis and Nasal Polyposis Associated With Severe Asthma,” International Journal of Immunopathology and Pharmacology 34 (2020): 2058738420950851.
19. Djukanovic R, Wilson SJ, Kraft M, Jarjour NN, Steel M et al. 2004. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am. J. Respir. Crit. Care Med. 170:583–93
20. Godse K, Mehta A, Patil S, Gautam M, Nadkarni N. Omalizumab—a review. Indian J Dermatol. 2015;60:381–4.
21. Noga O. et al., Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J. Allergy Clin. Immunol. 117, 1493–1499 (2006).