0. Cutting Edge Research for Food Allergy
Sara Anvari, M.D., M.Sc. Assistant Professor of Pediatrics Baylor College of Medicine/Texas Children’s Hospital
3rd Annual Advanced Practice Provider Conference April 16, 2016
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1. Outline Understanding Food Allergies Novel Food Allergy Investigations
Sublingual and Oral Immunotherapy
Epicutaneous Immunotherapy
Synbiotic Treatment Trials
Shrimp Allergy Study
Eosinophilic Esophagitis Trials
Future Directions - TCH Food Allergy Program
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2. Understanding Food Allergies
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3. Prevalence of Food Allergies in North America
Infant/Child
Adult
Milk
2.5%
0.3%
Egg
1.5%
0.2%
Wheat/soy
0.4%
Peanut
1.4%
0.6%
Tree nuts
0.5%
0.8%
Fish
0.1%
Shellfish 2%
Overall
5-8%
3-4%
Boyce JA et al. JACI. 2010;126:S1-S58 Sicherer et al. JACI. 2012

4. How Does Food Cause an Allergic Reaction?
Allergen Absorption
Allergen Processing
Egg
Food allergen
IgE mediated
IgE
APC
Antigen Presenting Cell
B cell
IL-4, IL-13
T cell
Non-IgE mediated
Histamine Release
IL-5, Eotaxin
Mast cell
Basophils
Hives, Vomiting, Swelling, Breathing Difficulty
Eos

5. Overview of Adverse Food Reactions
J Allergy Clin Immunol Nov;134(5): e43.
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6. Is There A Cure For Food Allergies?
No effective, FDA-approved treatment
Avoidance is the ONLY way to prevent an allergic reaction
Epinephrine is the only therapy to treat a severe reaction
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7. I. Sublingual and Oral Immunotherapy
Novel Food Allergy Investigations
I. Sublingual and Oral Immunotherapy
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8. What is the Goal of Immunotherapy?
Immune system no longer recognizes the food as harmful (Desensitization)
Cease mounting an immune response to the food when it is not given daily (Tolerance)
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9. Sublingual Immunotherapy
Smaller doses
Safer with less side effects
Not as effective as oral immunotherapy
Phase 2 Studies
Milk, peanut, hazelnut, peach, kiwi

10. Efficacy of Oral vs Sublingual Immunotherapymg
~10 mg
% Patients Tolerating Targeted Dose

11. Desensitization to Milk/Egg with Baked Goods
Three-fourths of milk allergic children can tolerate baked milk
Over half of egg allergic children can tolerate heated egg
Nowak-Wegrzyn et al. JACI. 2008: 122:342-7.
Lemon-Mulé et al. JACI. 2008:977-85
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12. LEAP AND LEAP-On Studies

13. Oral Immunotherapy – LEAP Study
Objective:
Determine if early introduction of peanut prevents peanut allergy
Methods:
High risk infants (severe eczema +/- egg allergy) 4-11 months old
Positive skin test (≤4mm wheal)
Negative skin test
Randomized into (2) groups for 5 yrs:
Peanut consumption
Avoidance
Peanut allergy was 5 times more likely to develop in children avoiding peanuts
DuToit et al NEJM 2015
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14. Oral Immunotherapy – LEAP-On Study
Objective:
Determine the effect of peanut avoidance for 1 year after early peanut consumption
Methods:
High risk infants (severe eczema +/- egg allergy) 4-11 months old
Positive skin test (≤4mm wheal)
Negative skin test
Randomized into (2) groups for 5 yrs:
Peanut consumption
Avoidance
Peanut avoidance for 12mo after 5yrs of ingestion
Prevalence of peanut allergy did not increase in the high-risk group following a 12-month period of peanut avoidance
DuToit et al NEJM 2015
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15. Peanut Oral Immunotherapy Trial
Initiated: July 2014
Enrolling: patients
Age: 5-16
Eligibility
Hx of peanut allergy
Peanut IgE >7 kU/L
Positive peanut skin test
Positive oral challenge to peanut
No history of asthma or uncontrolled eczema
No history of severe anaphylaxisd
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16. Peanut OIT Study Design
Build Up
Maintenance
Wash Out
Lab Work
Lab Work
Lab Work
Start
12 mo.
24 mo.
36 mo.
37 mo.
Skin Test
Food Challenge
Skin Test
Skin Test
Food Challenge
~20 peanuts
~1/100th peanut
= 200 mg
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17. Current OIT Dose Escalation
Peanut Dose (mg)
20 patients screened 11 have qualified Major reason for disqualification: inability to commit to study
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18. Peanut Oral Immunotherapy Skin Test Results
Screen
6 mo. post-OIT
Wheal Size (mm)
Pt 1
Pt 2
Pt 3
Pt 4
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19. II. Epicutaneous Immunotherapy
Novel Food Allergy Investigations
II. Epicutaneous Immunotherapy
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20. Epicutaneous Immunotherapy (Patch)
Increased thresholds for allergen in mouse models
Safe in humans
Preliminary studies show effectiveness in humans (250mcg dose)
Phase III trials underway (PEPITES)
DuPont et al. JACI DuPont et al. JACI. 2010
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21. III. Synbiotic Therapy Trials
Novel Food Allergy Investigations
III. Synbiotic Therapy Trials
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22. What are Probiotics
Probiotics: “Good”/”healthy” organisms (i.e. bacteria and yeasts) that may provide health benefits when consumed
Prebiotics: non-digestible “nutrition” to stimulate the growth of the healthy bacteria
Synbiotics: Probiotics + Prebiotics
Why is it important?
Hypothesized that allergies may be due to an imbalance between “good” and “bad” bacteria
Providing more “good” bacteria may help prevent the development of allergic disorders
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23. Why Are Synbiotics Important?
Probiotics and Peanut Oral Immunotherapy (PPOIT)
62 peanut allergic children
PPOIT vs Placebo for 18 mo
Underwent 2 separate oral peanut challenges
Challenge #1: Desensitization 89% vs 7%
Challenge #2 (after 2-5 week washout): Tolerance 82% vs 3%
Preliminary Studies Suggest Probiotics May Help with Tolerance Development
Tang et al, JACI 2014
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24. PRESTO Study (Prospective, Randomized Study to evaluate the Effectiveness of Synbiotics on Cow’s Milk Allergy Tolerance)
Objective: Determine if synbiotic formula allows for earlier cow’s milk tolerance and reduce # of other allergies
Criteria:
Diagnosis of cow’s milk allergy
Age < 13 months old
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25. PRESTO Study Multicenter International Trial
Start Formula
Start
12 mo.
24 mo.
36 mo.
6 yrs
Milk Challenge
Milk Challenge
Milk Challenge
Phone Follow-up
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26. Microbiome Influences on Development of Food Allergies in Children
Background:
Development and prevention of allergic disorders may be regulated by the bacteria on/in our body
Objective:
Characterize microbiome differences between the food allergic and non-food allergic siblings
Criteria:
Recruitment of healthy and food allergic siblings
Stool, saliva and skin samples collected at enrollment
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27. IV. Shrimp Allergy Study
Novel Food Allergy Investigations
IV. Shrimp Allergy Study
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28. Evaluating Immune Responses in Shrimp Allergic Patients
Pen a 1 IgE (kU/L)
Pen a 1 component testing could potentially be used as a marker to detect true shrimp allergy
Shrimp Tolerant
Shrimp Allergic
Tuano et al, In preparation
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29. V. Eosinophilic Esophagitis (EoE)
Novel Food Allergy Investigations
V. Eosinophilic Esophagitis (EoE)
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30. What is Eosinophilic Esophagitis (EoE)
Definition:
Chronic, immune-mediated disease characterized by:
Clinical symptoms of esophageal dysfunction
Difficulty swallowing, vomiting, poor weight gain
Histological eosinophil-predominant inflammation (endoscopy with biopsy)
>15 eos/hpf + histopathologic findings
Liacouras CA et al. JACI. 2011
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31. Standard EoE Treatment Schema
EoE Diagnosis
Dietary therapy
Elemental Diet
4 food Elimination Diet
Elimination Diet – Test directed
Medical therapy
Steroids
Topical or Systemic
Combination of Diet and Steroids
Comparison Trial of Diet vs. Medication
4 Food Elimination Trial Milk, Egg, Soy and Wheat
EoE Multicenter Trial

32. EoE Combination Therapy
Seth N, Chokshi N et al. Submitted
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33. Salivary Cytokines in EoE
Measured EoE relevant cytokines using magnetic high-sensitivity human multiplex assays (EMD Millipore, MA)
IL-4 & IL-5 could be markers of EoE detection and can be collected non-invasively via saliva
Hiremath et al., Ann Allergy Asthma Immunol, 2015
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34. Future Directions for TCH Food Allergy Program
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35. TCH Food Allergy Program Designated as a F. A. R. E
TCH Food Allergy Program Designated as a F.A.R.E. Center for Clinical Excellence
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36. Future Analyses / Studies
One year interim analysis of Peanut OIT after oral challenge
Phase 3 Center for Peanut OIT
Phase 3 Center for Epicutaneous “Patch” Immunotherapy
Phase 1 Center for Shrimp OIT
Phase 1 Center for Tree nut OIT
Phase 1 Center for Multi-Food OIT
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37. Conclusions
Partnering with the community and F.A.R.E to bring state of the art treatment and research
Oral immunotherapy trials have begun and are expanding
New methods for diagnosis and treatment of food allergic diseases
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38. Acknowledgements IAR Chief: Dr. Jordan Orange
Food Allergy Program Director: Dr. Carla Davis
TCH Food Allergy Program
Ms. Daisy Tran
Ms. Chivon McMullen-Jackson
Ms. Christina Cowperthwait
Ms. Theresa Aldape
Ms. Valerie Nichols
Ms. Kathy Green
Ms. Kathy Pitts
Ms. Lin-Lin Shao
EGID Clinic
Dr. Anthony Olive
Dr. Girish Hiremath
TCH Pathology
Dr. Sridevi Devaraj
TCH Center for Human Immunobiology
Dr. George Makedonas
Ms. Andrea Grimbergen
Dr. Alexandre Carisey
Dr. Emily Mace
Dr. Petra Netter
A/I Food Allergy Fellows
Dr. Karen Tuano
Dr. Atoosa Kourosh
Texas Children’s Research Resources Office
Ms. Supriya Parikh
Ms. Ann McMeans
Ms. Chiemenam Amaechi
Texas Children’s Clinical Research Center
Child Life Specialists, Our Patients and Donors of TCH Food Allergy Program