Transcript Title Page - Texas Children`s Hospital

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
Outline
1. Understanding Food Allergies
2. Novel Food Allergy Investigations
i.
ii.
iii.
iv.
v.
Sublingual and Oral Immunotherapy
Epicutaneous Immunotherapy
Synbiotic Treatment Trials
Shrimp Allergy Study
Eosinophilic Esophagitis Trials
3. Future Directions - TCH Food Allergy Program
Understanding Food Allergies
Prevalence of Food Allergies in
North America
Prevalence
Infant/Child
Adult
Milk
2.5%
0.3%
Egg
1.5%
0.2%
Wheat/soy
0.4%
0.3%
Peanut
1.4%
0.6%
Tree nuts
0.5%
0.8%
Fish
0.1%
0.4%
Shellfish
0.1%
2%
Overall
5-8%
3-4%
Boyce JA et al. JACI. 2010;126:S1-S58
Sicherer et al. JACI. 2012
How Does Food Cause an
Allergic Reaction?
Allergen Absorption
Allergen Processing
Food allergen
IgE mediated
IgE
B cell
APC
IL-4,
IL-13
T cell
Mast cell
Basophils
Histamine Release
Hives, Vomiting,
Swelling, Breathing
Difficulty
Antigen
Presenting
Cell
Non-IgE mediated
IL-5,
Eotaxin
Eos
Overview of Adverse Food Reactions
J Allergy Clin Immunol. 2014 Nov;134(5):1016-25.e43.
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
Novel Food Allergy Investigations
I. Sublingual and Oral Immunotherapy
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)
Sublingual Immunotherapy
• Smaller doses
• Safer with less side effects
• Not as effective as oral
immunotherapy
• Phase 2 Studies
• Milk, peanut, hazelnut,
peach, kiwi
% Patients Tolerating Targeted Dose
Efficacy of Oral vs Sublingual
Immunotherapy
2000-4000 mg
~10 mg
100
90
80
70
60
Milk
50
Peanut
40
Egg
30
20
10
0
Oral
Sublingual
Desensitization to Milk/Egg with Baked
Goods
Three-fourths of milk allergic
children can tolerate baked milk
Nowak-Wegrzyn et al. JACI. 2008: 122:342-7.
Over half of egg allergic children can
tolerate heated egg
Lemon-Mulé et al. JACI. 2008:977-85
LEAP AND LEAP-On Studies
Oral Immunotherapy – LEAP Study
• Objective:
– Determine if early introduction
of peanut prevents peanut
allergy
Peanut allergy was 5 times
more
likely
to
develop
• Methods:
in children avoiding
– High peanuts
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
DuToit et al NEJM 2015
Oral Immunotherapy – LEAP-On Study
• Objective:
– Determine the effect of peanut
avoidance for 1 year after early
peanut consumption
Prevalence of peanut •allergy
did not increase in
Methods:
– Higharisk
infants (severe
eczema
the high-risk group following
12-month
period
+/- egg allergy) 4-11 months old
of peanut avoidance
• 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
DuToit et al NEJM 2015
Peanut Oral Immunotherapy Trial
Initiated: July 2014
Enrolling: 15-20 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
Peanut OIT Study Design
Lab Work
Wash Out
Maintenance
Build Up
Lab Work
Lab Work
Start
~1/100th
peanut
12 mo.
Skin
Test
Food
Challenge
24 mo.
Skin
Test
36 mo. 37 mo.
Skin Food
Test Challenge
~20
peanuts
= 200 mg
Current OIT Dose Escalation
4500
4000
Pt 1
Peanut Dose (mg)
3500
Pt 2
3000
Pt 3
Pt 4
2500
Pt 5
Pt 6
2000
Pt 7
Pt 8
1500
Pt 9
1000
Pt 10
Pt 11
500
0
Initial Peanut Dose (mg)
Current Peanut Dose (mg)
Peanut Oral Immunotherapy
Skin Test Results
50
Screen
Wheal Size (mm)
40
6 mo. post-OIT
30
20
10
0
Pt 1
Pt 2
Pt 3
Pt 4
Novel Food Allergy Investigations
II. Epicutaneous Immunotherapy
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. 2014
DuPont et al. JACI. 2010
Novel Food Allergy Investigations
III. Synbiotic Therapy Trials
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
Why Are Synbiotics Important?
• Probiotics and Peanut Oral Immunotherapy
(PPOIT) Studies Suggest Probiotics May Help
Preliminary
– 62 peanut
children
withallergic
Tolerance
Development
– 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%
Tang et al, JACI 2014
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:
1. Diagnosis of cow’s milk allergy
2. Age < 13 months old
PRESTO Study
Multicenter International Trial
Start
Formula
Start
12 mo.
24 mo.
36 mo.
Milk
Milk
Milk
Challenge Challenge Challenge
6 yrs
Phone
Follow-up
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 nonfood allergic siblings
• Criteria:
– Recruitment of healthy and food
allergic siblings
– Stool, saliva and skin samples
collected at enrollment
Novel Food Allergy Investigations
IV. Shrimp Allergy Study
Evaluating Immune Responses in Shrimp
Allergic Patients
Pen a 1 IgE (kU/L)
12
10
Pen a 1 IgE (kU/L)
Pen a 1 component testing could potentially be used
as a marker8 to detect true shrimp allergy
6
4
3.79
2
0
Tuano et al, In preparation
0.09
Shrimp
Tolerant
Shrimp
Allergic
Novel Food Allergy Investigations
V. Eosinophilic Esophagitis (EoE)
What is Eosinophilic Esophagitis
(EoE)
• Definition:
– Chronic, immune-mediated
disease characterized by:
• Clinical symptoms of esophageal
dysfunction
– Difficulty swallowing,
vomiting, poor weight gain
www.community.kidswithfoodallergies.org
• Histological eosinophilpredominant inflammation
(endoscopy with biopsy)
– >15 eos/hpf + histopathologic
findings
Liacouras CA et al. JACI. 2011
Standard EoE
Treatment Schema
Comparison Trial
of Diet vs. Medication
EoE
Diagnosis
Dietary
therapy
Elemental
Diet
4 food
Elimination
Diet
4 Food Elimination Trial
Milk, Egg, Soy and Wheat
Medical
therapy
Elimination
Diet – Test
directed
Steroids
Topical or
Systemic
EoE Multicenter Trial
Combination
of Diet and
Steroids
EoE Combination Therapy
Seth N, Chokshi N et al. Submitted
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
Future Directions for
TCH Food Allergy Program
TCH Food Allergy Program
Designated as a F.A.R.E. Center for
Clinical Excellence
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
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
Acknowledgements
• IAR Chief: Dr. Jordan Orange
• Food Allergy Program Director:
Dr. Carla Davis
• TCH Food Allergy Program
–
–
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–
–
–
–
–
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
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–
–
–
–
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