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

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Presentation on theme: "Bret Haymore, MD FAAAAI, FACAAI Food Oral Desensitization: Potential & Pitfalls."— Presentation transcript:

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

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

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 – Generally by school age Significant adverse effect on quality of life –Greater than some other chronic diseases (i.e., type 1 diabetes) Cummings 2010 Allergy 65(8): No proactive therapy available Fleischer 2007 Curr.Allergy Asthma Rep. 7: Skripak 2007 J Allergy Clin.Immunol. 120: ~20% of Children with peanut allergy outgrow the disease

6 PeanutSensitization Burks AW. Lancet 2008;371,9623:

7 PeanutSensitization Burks AW. Lancet 2008;371,9623:

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

9 Initial Food Allergy StudyGoals 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 immunologic markers associated with the treatment Identify the mechanisms of the changes brought on by the treatment

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

11 PeanutOITBlinded StudyDesign 4000 mg Jones et al. ‐AAAAI peanut = 300 mg Initial escalation day – 6 mg Desensitization Food Challenge #1 (OFC 1) Dose Escalation Maintenance

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

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

15 SerumLevels of Peanut-Specific IgEandIgG4 ChangewithTreatment Jones et al. -AAAAI 2010 ImmunoCAP-FEIA (Phadia)

16 SerumLevels of Peanut-Specific IgEandIgG4 ChangewithTreatment Jones et al. -AAAAI 2010 ImmunoCAP-FEIA (Phadia)

17 Peanut OIT Allergen-Specific T cells Basophil markers - %CD63 – Significant change over first few months of OIT Peanut-specific CD4+CD25+Foxp3+ – T-Regulatory cells T cells increased at 12 months decreased thereafter 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 3 Years of OIT 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 ofImmunotherapy Oral IT (OIT) – swallowed with food Sublingual IT (SLIT) –sublingually then swallowed Differences –amount of protein, route?, digestion?, possibility of causing tolerance? OIT SLIT

20 Sublingual Immunotherapy (SLIT) 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 Total home 4% 3% 2% 1% (3) 3 rd study (CoFAR-NIH) 0% Skin Upper Resp ChestAbdomen - Adolescents and adults – 3 year study Symptom percent of home doses 4.6% doses (n=4737) 0.6% oropharyngeal non-oropharyngeal 0.7% 0% SLIT – Peanut allergic adults and children (2) 2 nd blinded study (Duke) – children Bird et al. AAAAI 2010, Kim et al. AAAAI 2010

21 SLIT Causes Clinical and Mast Cell Desensitization 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 SLIT – peanut allergic children and adults 2 nd blinded study (Duke) – children Bird et al. AAAAI 2010, Kim et al. AAAAI 2010

22 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 SLIT Causes Clinical and Mast Cell Desensitization SLIT – peanut allergic children and adults 2 nd blinded study (Duke) – children Bird et al. AAAAI 2010, Kim et al. AAAAI 2010

23 – then Johns Hopkins/Duke Study – MilkAllergy Combined SLIT/OIT for milk – ~5 months Pre-study milk Oral FoodChallenge –Dose at reaction ~40 mg Initial SLIT in allgroups 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 2-7 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 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 Studies needed to understand possible clinical benefit and mechanism RCTs are in process Optimizing pharmacokinetics, targeting correct populations

26 Questions? Food Allergy Immunotherapy

27 Contact Dr. Bret Haymore ; 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


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