What information is available on the use of omalizumab for IgE-mediated food allergy?

Introduction
Food allergies have increased in prevalence in the United States (U.S.) over the past 30 years.1-5 Data from the Centers for Disease Control and Prevention (CDC) National Health Interview Surveys 2021 reported 6.7% of adults and 5.8% of children aged 0-17 years had a food allergy.4,5 Food allergies can be categorized as immunoglobulin E (IgE)-mediated, non-IgE mediated, or mixed, based on the immune mechanisms involved in the reaction.1,6 For IgE-mediated food allergies, food-specific IgE antibodies are present, which leads to the release of multiple mediators including histamine. The allergic response occurs acutely in most cases, soon after ingestion or exposure to the offending food (ie, within 2 hours); symptoms of a reaction may include urticaria, angioedema, erythema, bronchospasm, nausea, vomiting, and anaphylaxis.

Patients with anaphylaxis require emergency medical treatment, including prompt administration of epinephrine.7 In addition to the potential emergency department visits, there may be a significant psychosocial burden for patients and families in the risk of exposure to the allergen.1 An important goal in the management of food allergy is to achieve a sense of control by reducing the risk associated with accidental exposure.8

Overview of omalizumab
Omalizumab is an anti-IgE, recombinant DNA-derived, humanized monoclonal antibody.9 It inhibits the binding of IgE to high-affinity IgE receptors on the surface of mast cells, basophils, and dendritic cells, resulting in down-regulation. It is given as a subcutaneous injection every 2 or 4 weeks, with its dosage dependent on the specific indication, serum total IgE level measured before the start of treatment, and body weight. Omalizumab has a boxed warning on the risk of anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, or angioedema of the throat or tongue. Because of this risk, therapy should be initiated in a healthcare setting; patients should be closely observed after administration, and healthcare providers should be prepared to manage anaphylaxis. Additional warnings, precautions, and adverse reactions associated with omalizumab may be found in the product’s prescribing information.

Omalizumab was first approved by the U.S. Food and Drug Administration (FDA) in 2003 for adults and adolescents 12 years and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.10 Since 2003, omalizumab has gained several other indications, including chronic rhinosinusitis with nasal polyps (CRSwNP) in adults and chronic spontaneous urticaria (CSU) in adults and adolescents 12 years and older.9,10 In February 2024, it was approved for use in IgE-mediated food allergy, in conjunction with food allergen avoidance, in adult and pediatric patients aged 1 year and older for the reduction of Type I allergy reactions, including anaphylaxis, that may occur with accidental exposure to one or more foods. It is not indicated for the emergency treatment of allergic reactions, including anaphylaxis.

Standards of care updates for IgE-mediated food allergy
Several professional organizations have updated guidelines or released statements related to standards of care for IgE-mediated food allergy since omalizumab’s regulatory approval.11-13 The European Academy of Allergy and Clinical Immunology (EAACI) guidelines on the management of IgE-mediated food allergy recommend food allergen avoidance.11 Additional recommendations include the development and utilization of individualized treatment plans, prescription epinephrine for patients or caregivers to carry, patient and caregiver education on recognition of anaphylaxis, and instructions for patients and caregivers on epinephrine use. For patients who are eligible for allergen-specific immunotherapy, its use is recommended under the guidance of an experienced clinical team. Allergen-specific immunotherapy, often referred to as immunotherapy, involves the administration of an allergen to allergic patients. Types of immunotherapy include oral, epicutaneous, and sublingual.11 Oral immunotherapy consists of oral daily ingestion, starting below a patient’s threshold dose that would elicit an allergic reaction.8 The allergen dose would be increased over time to increase clinical tolerance to the offending food. For children and adolescents with IgE-mediated peanut allergy, peanut oral immunotherapy is recommended to achieve desensitization; egg and milk oral immunotherapy are suggested in pediatric patients (generally >4 years) to achieve desensitization to these food allergens.11 Omalizumab, a biologic, is also suggested by the EAACI to achieve desensitization.

A guidance was also published by a work group of a subcommittee within the American Academy of Allergy, Asthma & Immunology (AAAAI) that discusses use and implementation of omalizumab as food allergy treatment.12 This report includes several consensus statements, including that omalizumab can be a treatment option as part of a shared decision-making process with other therapies. The potential for omalizumab therapy would apply to patients with one or more IgE-mediated food allergy, without restriction based on disease severity or failure of alternative food allergy therapies. Patients who are candidates for omalizumab therapy should have a qualifying total IgE serum level for proper dosing and evidence of sensitization. Patients who use omalizumab for this indication should still adhere to strict food allergen avoidance and continue to carry epinephrine to protect against accidental ingestions.

A statement from the Global Allergy and Asthma Excellence Network (GA2LEN) was also published on the potential for omalizumab in food allergy management.13 Based on their systematic review and meta-analysis of use of omalizumab alone or in conjunction with oral immunotherapy in the literature, it was concluded that there is now sufficient evidence to recommend omalizumab as monotherapy in select patients. In addition, adding omalizumab to oral immunotherapy may increase tolerance of immunotherapy with fewer reactions. However, its use may be limited by cost and its administration as an injection.

Literature on omalizumab for IgE-mediated food allergy
The efficacy of omalizumab for IgE-mediated food allergy is largely supported by data from a randomized, double-blind placebo-controlled trial (OUtMATCH).9,14 Information for the first analysis of this study in pediatric patients is listed in the Table. A literature search was also conducted to identify additional large clinical controlled trials or meta-analyses related to omalizumab’s efficacy for this indication. Relevant studies identified are also listed in the Table.

Table. Overview of clinical efficacy for omalizumab in IgE-mediated food allergy.14-16
Study design and durationSubjectsInterventionsResultsConclusions
Meta-analyses
Riggioni et al 202415

MA of IT and biologics

Duration: varied (range 6 to 260 weeks)		N=121 studies (10 for biologics [8 for omalizumab, 1 for etokimaba, 1 for talizumaba]; 111 for IT) assessing IT and biologics in the management of IgE-mediated food allergy in adults and pediatric patients

Allergies assessed: peanuts, cow’s milk, multiple		Omalizumab SC at varying dosages (n=8 studies; 6 explicitly co-administered with OIT)

Comparators for included omalizumab studies:
Placebo (n=6), allergen avoidance (n=1), or none (n=1)		Primary:
Desensitization rate: 145/188 for omalizumab vs. 38/92 for control (rate ratio, 2.17; 95% CI, 1.22 to 3.85; in favor of omalizumab)

Secondary:
Sustained unresponsiveness or remission, or higher dose desensitization (n=4 studies): 56/93 for omalizumab vs. 13/49 for control (rate ratio, 2.42; 95% CI, 0.90 to 6.50)

Safety:
Few studies included in omalizumab MA included AEs

Safety was generally in favor of placebo

One trial reported 4 serious events in active arm (including 2 anaphylaxis) vs. 3 in the placebo arm		Biologics (including omalizumab) and IT, alone or in combination, are effective in achieving desensitization while on active treatment
Zuberbier et al 202316

MA of omalizumab as monotherapy or omalizumab plus OIT

Pre-omalizumab treatment period: 17-22 weeks

Omalizumab treatment period: 9-22 weeks		N=36 RCTs in adults and pediatric patients of any age with a clinician-diagnosed IgE-mediated food allergy (one or multiple)

Allergies assessed: peanuts, cow’s milk, eggs, nuts, multiple		Omalizumab SC at varying dosages

Comparators included omalizumab pretreatment data or placebo		Efficacy:
Increase of tolerated dose to multiple foods with monotherapy (n=4 studies): Risk ratio, 24.88; 95%CI, 6.35 to 97.45; p<0.001; in favor of omalizumab vs. pre-treatment

Increase of tolerated dose to multiple foods with omalizumab plus OIT (n=2 studies): Risk ratio, 1.72; 95% CI, 1.16 to 2.55; p=0.01; in favor of omalizumab plus OIT vs. placebo

Safety:
No major safety concerns identified; anaphylaxis reported in patients receiving omalizumab as monotherapy and omalizumab plus OIT

Most notable AEs: gastrointestinal, general, respiratory, thoracic, and mediastinal disorders		Omalizumab as monotherapy or as an adjunct to OIT can support increased tolerated dosages to multiple foods
Controlled clinical trial
Wood et al 202414

OUtMATCH

Phase 3, MC, DB, PC, RCT

16 weeks		N=177 pediatric patients 1 to 17 years of age who were allergic to peanuts and at least two other foods (cashew, milk, egg, walnut, wheat, and hazelnut)

Key exclusion: previous IT for any protocol-specified foods

Median age: 7 years

Baseline median total IgE level: 700 IU/mLb		Omalizumab SC, dosage based on weight and IgE levels, every 2 to 4 weeks (n=118)

Placebo (n=59)

Both study groups instructed to avoid food allergens		Primary:
Ingestion of peanut protein in single dose of 600 mg or more without dose-limiting symptoms: 67% for omalizumab vs. 7% for placebo (between-group difference, 60%; 95% CI, 47 to 70; p<0.001)

Secondary:
Consumption of cashew in single dose of at least 1000 mg without dose-limiting symptoms: 41% for omalizumab vs. 3% for placebo (between-group difference, 38%; 95% CI, 19 to 52; p<0.001)

Consumption of egg in single dose of at least 1000 mg without dose-limiting symptoms: 67% for omalizumab vs 0% for placebo (between-group difference, 67%; 95% CI, 46 to 79; p<0.001)

Consumption of milk in single dose of at least 1000 mg without dose-limiting symptoms: 66% for omalizumab vs 10% for placebo (between-group difference, 56%; 95% CI, 30 to 74; p<0.001)

Safety:
AEs occurred in 63.6% of patients who received omalizumab and 78.0% of patients who received placebo

The most common AEs in the omalizumab group were hypersensitivity (21.2%), injection site reaction (9.3%), and coronavirus infection (6.8%); rates were similar across the two groups except for injection site reaction		Omalizumab was more effective than placebo for increasing the reaction threshold for peanut and other common food allergens in pediatric patients with multiple food allergies
Abbreviations: AEs=adverse events; CI=confidence interval; DB=double-blind; IgE=immunoglobulin E; IT=immunotherapy; MA=meta-analysis; MC=multicenter; OIT=oral immunotherapy; PC=placebo-controlled; RCT=randomized controlled trial; SC=subcutaneous.
aNot available in the United States.
bInclusion criteria required baseline body weight and total serum IgE level suitable for omalizumab dosing.

Conclusion
Omalizumab is a new option for the treatment of IgE-mediated food allergy in adult and pediatric patients 1 year of age or older. As shown in the OuTMATCH trial, it effectively increases the threshold of several allergens, including peanuts, milk, and eggs. Additional analysis may provide additional information as to omalizumab’s place in therapy versus or in conjunction with allergen-specific immunotherapy. The potential for anaphylaxis with the use of omalizumab in of itself may be of concern to some clinicians, patients, and caregivers. Its use in therapy should be part of a shared decision-making process; patients should continue allergen avoidance and patients and caregivers should continue to carry epinephrine.

References

  1. Dantzer JA, Wood RA. Anti-IgE and food allergy. J Allergy Clin Immunol. 2025;155(1):1-11. doi:10.1016/j.jaci.2024.10.020
  2. Bégin P, Waserman S, Protudjer JLP, Jeimy S, Watson W. Immunoglobulin E (IgE)-mediated food allergy. Allergy Asthma Clin Immunol. 2024;20(Suppl 3):75. doi:10.1186/s13223-024-00930-7
  3. Jackson KD, Howie LD, Akinbami LJ. Trends in allergic conditions among children: United States, 1997-2011. NCHS Data Brief. 2013;(121):1-8.
  4. Zablotsky B, Black LI, Akinbami LJ. Diagnosed allergic conditions in children aged 0–17 years: United States, 2021. NCHS Data Brief. 2023;(459):1-8. doi:10.15620/cdc:123250
  5. Ng AE, Boersma P. Diagnosed allergic conditions in adults: United States, 2021. NCHS Data Brief. 2023;(460):1-8. doi:10.15620/cdc:122809
  6. Abrams EM, Sicherer SH. Diagnosis and management of food allergy. CMAJ. 2016;188(15):1087-1093. doi:10.1503/cmaj.160124
  7. Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134(5):1016-25.e43. doi:10.1016/j.jaci.2014.05.013
  8. Bégin P, Chan ES, Kim H, et al. CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy. Allergy Asthma Clin Immunol. 2020;16:20. doi:10.1186/s13223-020-0413-7
  9. Xolair. Prescribing information. Genentech; 2024.
  10. U.S. Food and Drug Administration. Drugs@FDA: FDA-approved drugs. U.S. Food and Drug Administration website. Accessed February 24, 2025. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
  11. Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the management of IgE-mediated food allergy. Allergy. 2025;80(1):14-36. doi:10.1111/all.16345
  12. Anagnostou A, Bird JA, Chinthrajah S, et al. The use and implementation of omalizumab as food allergy treatment: Consensus-based guidance and Work Group Report of the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2025;155(1):62-69.e1. doi:10.1016/j.jaci.2024.09.031
  13. Zuberbier T, Muraro A, Nurmatov U, et al. GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management. Clin Transl Allergy. 2024;14(11):e70002. doi:10.1002/clt2.70002
  14. Wood RA, Togias A, Sicherer SH, et al. Omalizumab for the treatment of multiple food allergies. N Engl J Med. 2024;390(10):889-899. doi:10.1056/NEJMoa2312382
  15. Riggioni C, Oton T, Carmona L, Du Toit G, Skypala I, Santos AF. Immunotherapy and biologics in the management of IgE-mediated food allergy: Systematic review and meta-analyses of efficacy and safety. Allergy. 2024;79(8):2097-2127. doi:10.1111/all.16129
  16. Zuberbier T, Wood RA, Bindslev-Jensen C, et al. Omalizumab in IgE-mediated food allergy: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2023;11(4):1134-1146. doi:10.1016/j.jaip.2022.11.036

Prepared by:
Jacqueline Wasynczuk, PharmD
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago Retzky College of Pharmacy

March 2025

The information presented is current as February 24, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.