1. Bret Haymore, MD FAAAAI, FACAAI
Food Oral Desensitization:
Potential & Pitfalls
Bret Haymore, MD FAAAAI, FACAAI

2. OBJECTIVES Understand prevalence and evaluation of patients
with suspected food allergy
- Understand management of food allergy
Understand role of food desensitization in
management of food allergy

3. DISCLOSURES
NONE

4. Background: Food Allergy • Prevalence: •–
3 million school age children (3.9%)
18% increase since 1997
Branum 2009 Pediatrics. 124: •
7 most common food allergens in U.S. –
Milk, egg, peanut, tree nuts, shellfish, soy, wheat •
Peanut allergy
Prevalence ~1%
Most common cause of anaphylaxis in children presenting to ED
Most common cause of fatal food anaphylaxis •
Standard of care –
Self-injectable epinephrine/antihistamines
Avoidance of only foods appropriately diagnosed
Bock, J Allergy Clin Immunol 2007
Vander Leek, J Peds 2000

5. Background: Food Allergy•
Accidental exposures –
Incidence ~33% per year
Peanut IgE can’t predict severity
Vast majority of fatalities in patients with known allergy
~20% of Children with peanut allergy outgrow the disease • –
Generally by school age •
Significant adverse effect on quality of life –
Cummings 2010 Allergy 65(8):
Greater than some other chronic diseases (i.e., type 1 diabetes) •
No proactive therapy available
Fleischer 2007 Curr.Allergy Asthma Rep. 7:
Skripak 2007 J Allergy Clin.Immunol. 120:

6. Peanut
Sensitization
Burks AW. Lancet 2008;371,9623:

7. Peanut
Sensitization
Burks AW. Lancet 2008;371,9623:

8. Development of Treatment Options
Allergen non-specific
Anti-IgE – not stand alone treatment
Leung, Sampson, et al. NEJM 2003; 348:986-93
Li, X 2003 J.Allergy Clin.Immunol. 112:
• Chinese herbal medicine – in trials now •
Allergen-specific •
Engineered recombinant protein – reduced
Oral immunotherapy (OIT)
Sublingual immunotherapy (SLIT)
IgE binding
Skripak Current Opinion In Immunology 2008,20:

9. Initial Food Allergy Study Goals•
Goals of treatment are two-fold
– Clinical desensitization •
tolerate more food before an accidental reaction
– Eventual clinical tolerance •
off treatment •
Goals of research on food allergy treatment
Identify the mechanisms of the changes brought on by the treatment
– Identify immunologic markers associated with the treatment

10. Methods of Immunotherapy • Oral IT (OIT) • Sublingual IT (SLIT) •–
swallowed with food •
Sublingual IT (SLIT) –
sublingually then swallowed •
Differences –
possibility of causing tolerance?
amount of protein, route?, digestion?,
OIT
SLIT

11. Peanut OIT Blinded Study Design 4000 mg Jones et al. ‐AAAAI 2010
Maintenance
4000 mg
Dose Escalation
Food Challenge #1
(OFC 1)
Desensitization
Initial escalation day – 6 mg
1 peanut = 300 mg
Jones et al. ‐AAAAI 2010

12. Meet criteria for assessing tolerance
Peanut OIT Blinded Study Design
Meet criteria for assessing tolerance
Maintenance
Off OIT
4000 mg
1 mo
Dose Escalation
Food Challenge #1
(OFC 1)
Food Challenge #2 (OFC 2)
Desensitization
Food Challenge #3 (OFC3)
Initial escalation day – 6 mg
Tolerance
1 peanut = 300 mg
Jones et al. ‐AAAAI 2010

13. Peanut OIT – Blinded Study
•Any peanut-allergic subject – unless accompanied by significant hypotension
•25 subjects – 16 - active treatment; 9 - placebo
•All subjects - maximum dose of 6 mg (initial day);
4000 mg during build-up * * *
P=.008
Jones et al. -AAAAI 2010

14. Peanut OIT – Blinded Study
•Any peanut-allergic subject – unless accompanied by significant hypotension
•25 subjects – 16 - active treatment; 9 - placebo
•All subjects - maximum dose of 6 mg (initial day);
4000 mg during build-up * * * * *
P=.008 *
P=.001
Jones et al. -AAAAI 2010

15. Levels of Peanut-Specific IgE and IgG4
Serum
Levels of Peanut-Specific IgE
and
IgG4
Change
with
Treatment
Jones et al. -AAAAI 2010
ImmunoCAP-FEIA (Phadia)

16. Levels of Peanut-Specific IgE and IgG4
Serum
Levels of Peanut-Specific IgE
and
IgG4
Change
with
Treatment
Jones et al. -AAAAI 2010
ImmunoCAP-FEIA (Phadia)

17. Allergen-Specific T cells
Peanut OIT •
Basophil markers - %CD63
– Significant change over first few months of
OIT •
Peanut-specific CD4+CD25+Foxp3+
– T-Regulatory cells
T cells •
decreased thereafter
increased at 12 months •
Peanut-specific cytokines
– Decreased – pro-allergic cytokines - IL-4, IL-5, IL-13
– Increased – regulatory cytokines - IL-10, TGF-ß
Breslin et al. AAAAI
Jones, Burks et al. – J Allergy Clin Immunol – August 2009

18. Permanent Tolerance Develops after
3 Years of OIT
Permanent Tolerance Develops
after •
27 subjects - on OIT >36 months •
13/27 (48%) passed food challenges
• Off treatment
• These subjects remain off OIT and ingest peanut in their diet
to peanuts
Varshney, Jones, Burks et al. AAAAI 2010

19. Methods of Immunotherapy • Oral IT (OIT) • Sublingual IT (SLIT) •–
swallowed with food •
Sublingual IT (SLIT) –
sublingually then swallowed •
Differences –
possibility of causing tolerance?
amount of protein, route?, digestion?,
SLIT
OIT

20. - Adolescents and adults
Sublingual Immunotherapy (SLIT)
SLIT – Peanut allergic adults and children 5%
(1) Initial pilot study (Duke)
- Adolescents and adults
Laubach, Burks, et al. J Allergy Clin Immunol 2008;121:S96
Bird et al. J Allergy Clin Immunol 2009
4.6%
Total home
doses
(n=4737)
0.6%
oropharyngeal
non-oropharyngeal
0.7% 4%
(2) 2nd blinded study (Duke) – children
Bird et al. AAAAI 2010, Kim et al. AAAAI 2010 3%
percent of home doses 2% 1%
(3)
3rd
study (CoFAR-NIH) 0%
3 year study
- Adolescents and adults – 0%
Skin
Upper Resp
Chest
Abdomen
Symptom

21. SLIT Causes Clinical and Mast Cell Desensitization
SLIT – peanut allergic children and adults
2nd blinded study (Duke) – children
Bird et al. AAAAI 2010, Kim et al. AAAAI 2010 •
Peanut extract – given sublingually •
8 gtts (2 mg) maintenance dose
Updosing period – 6 months; Maintenance dosing – 6 months
Double-blind, placebo-controlled food challenge (DBPCFC) at 12 months
DBPCFC

22. SLIT Causes Clinical and Mast Cell Desensitization
SLIT – peanut allergic children and adults
2nd blinded study (Duke) – children
Bird et al. AAAAI 2010, Kim et al. AAAAI 2010 •
Peanut extract – given sublingually •
8 gtts (2 mg) maintenance dose
Updosing period – 6 months; Maintenance dosing – 6 months
Double-blind, placebo-controlled food challenge (DBPCFC) at 12 months
DBPCFC
Peanut prick skin test

23. Johns Hopkins/Duke Study – Milk Allergy•
Combined SLIT/OIT for milk – ~5 months •
Pre-study milk Oral Food
Challenge –
Dose at reaction ~40 mg
– then •
Initial SLIT in all
groups 1. 2. 3.
Continued SLIT
A (low) OIT
B (higher) OIT
Keet, Burks, Wood et al JACI 2010

24. Immunotherapy Comparison
Type of Therapy OIT SLIT
Daily dose mg mg
Side effects GI, systemic, fever, Oral-pharyngeal, exercise
Desensitization Large effect Smaller effect
Long term tolerance Unknown Unknown

25. Immunotherapy for Food Allergy - Future•
OIT/SLIT – still investigational
Studies needed to understand possible clinical benefit and mechanism
RCTs are in process
Optimizing pharmacokinetics, targeting correct populations •
Determine mechanism of action of OIT/SLIT –
Basophils/mast cells, humoral, cellular •
Determine if food IT induces –
Desensitization without/and clinical tolerance
Is desensitization only worthwhile? •
Goal: development of active treatment for food allergy

26. Food Allergy Immunotherapy
Questions?

27. Contact Dr. Bret Haymore 405.896.2268; 918.856.6077
NW OKC, Midwest City, Broken Arrow

28. What does an Allergist-Immunologist Treat
Environmental allergy (hay fever)
Immunotherapy (allergy shots/drops)
Asthma, chronic cough
Chronic sinusitis
Food allergy / Food desensitization
Atopic dermatitis/eczema
Contact dermatitis
Hives/angioedema
Stinging insect allergy
Immunotherapy
Medication allergy / oral challenge / desensitization
Penicillin skin testing
Aspirin desensitization
Eosinophilic Esophagitis
Immune deficiencies / recurrent infections