What is the role of Omalizumab (anti-IgE antibody) in the treatment of food allergy?

Role of Omalizumab in Food Allergy Treatment

Omalizumab is now recommended as an effective monotherapy for patients with multiple IgE-mediated food allergies, particularly in those who have experienced severe reactions or have multiple food allergies, as it significantly increases reaction thresholds and improves safety. 1

Current Status and Mechanism of Action

• Omalizumab (Xolair) is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobulin E (IgE), inhibiting its binding to high-affinity IgE receptors (FcεRI) on mast cells, basophils, and dendritic cells 2
• The FDA has recently approved omalizumab for the treatment of IgE-mediated food allergies, making it the first biologic monotherapy available for this indication 3
• Omalizumab works by reducing serum free IgE levels and down-regulating FcεRI expression, thereby inhibiting IgE-mediated inflammatory responses 2

Evidence for Efficacy

• The landmark OUtMATCH study (2024) demonstrated that 67% of participants receiving omalizumab could tolerate 600mg or more of peanut protein in a single dose without dose-limiting symptoms, compared to only 7% in the placebo group (p<0.001) 1
• Similar significant improvements were seen with other common allergens including cashew (41% vs 3%), milk (66% vs 10%), and egg (67% vs 0%) 1
• Omalizumab has shown effectiveness in patients as young as 1 year of age with multiple food allergies 1
• A pilot study of 22 patients with persistent asthma and concomitant IgE-mediated food allergy showed that all patients (100%) experienced significant improvement with decreased clinical symptoms upon reexposure to sensitized foods after omalizumab treatment 4

Adjunctive Use with Oral Immunotherapy (OIT)

• Multifood OIT with adjunctive omalizumab has been found to be safe and effective, and has been shown to rapidly decrease time to desensitization to multiple foods 5
• A systematic review and meta-analysis found that OIT combined with omalizumab led to significantly higher rates of desensitization, allowing patients to tolerate higher doses of allergens in a shorter timeframe compared to OIT alone 6
• Omalizumab as an adjunct to OIT was associated with a reduction in adverse reactions, including anaphylaxis, and improved treatment adherence 6

Current Guideline Recommendations

• Most current food allergy guidelines still recommend strict allergen avoidance as the standard approach for food allergy management 5
• The American Academy of Allergy, Asthma, and Immunology recommends strict avoidance plus emergency preparedness, including an anaphylaxis management plan with ready access to injectable epinephrine 7
• Some regional guidelines, such as those from Colombia, Brazil, and Argentina, support the use of monoclonal antibodies like omalizumab in food allergy management 5
• However, many international guidelines, including those from Australia and Asia, do not currently support biologicals alone or in association with immunotherapy for food allergy treatment 5

Patient Selection and Clinical Considerations

• Omalizumab is particularly valuable for patients with:
  • Multiple food allergies (approximately 45% of individuals with food allergy) 5
  • History of severe reactions or anaphylaxis 7
  • Adolescents with peanut and tree nut allergies who are at highest risk for life-threatening anaphylaxis 7
• Omalizumab increases the threshold at which allergic reactions occur, providing protection against small accidental exposures 7
• Despite treatment with omalizumab, patients should still maintain strict food avoidance and carry emergency epinephrine 7

Safety Profile

• The safety profile of omalizumab in food allergy appears similar to its established profile in other allergic conditions 1
• The most common adverse effect specific to omalizumab treatment is injection-site reactions 1
• A case report of a 51-year-old woman with oral steroid-dependent severe asthma and multiple food allergies showed that long-term omalizumab treatment (6 years) resulted in disappearance of food allergy symptoms 8

Limitations and Future Directions

• The long-term sustainability of tolerance after omalizumab discontinuation remains uncertain 6
• Further research is needed on optimal treatment duration, dosing schedules, and cost-effectiveness 3, 6
• Research into combination of multi-OIT with omalizumab and other biologics like dupilumab is ongoing 5

Clinical Algorithm for Omalizumab Use in Food Allergy

1. Patient Assessment:

   • Confirm IgE-mediated food allergy through history, skin tests, and/or specific IgE testing 5
   • Identify patients with multiple food allergies or history of severe reactions 7, 1

2. Candidate Selection:

   • Consider omalizumab for patients with documented IgE-mediated food allergies to multiple foods 7, 1
   • Prioritize patients with previous anaphylaxis or those at high risk (e.g., adolescents with peanut/tree nut allergies) 7

3. Treatment Administration:

   • Dose based on weight and IgE levels 1
   • Administer subcutaneously every 2-4 weeks 1
   • Standard treatment duration of 16-20 weeks in clinical trials 1

4. Monitoring:

   • Assess for injection site reactions 1
   • Continue strict allergen avoidance and emergency preparedness during treatment 7
   • Consider food challenges under medical supervision to assess treatment efficacy 1