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Bret Haymore, MD FAAAAI, FACAAI

Food Oral Desensitization: Potential & Pitfalls. Bret Haymore, MD FAAAAI, FACAAI. OBJECTIVES. Understand prevalence and evaluation of patients with suspected food allergy - Understand management of food allergy Understand role of food desensitization in

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Bret Haymore, MD FAAAAI, FACAAI

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  1. 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. 124:1549-55 • 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 – – Avoidance of only foods appropriately diagnosed Self-injectable epinephrine/antihistamines Vander Leek, J Peds 2000 Bock, J Allergy Clin Immunol 2007

  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 – Greater than some other chronic diseases (i.e., type 1 diabetes) Cummings 2010 Allergy 65(8):933-945 No proactive therapy available Fleischer 2007 Curr.Allergy Asthma Rep. 7:175-181 Skripak 2007 J Allergy Clin.Immunol. 120:1172-1177 •

  6. Peanut Sensitization Burks AW. Lancet 2008;371,9623:1538-1546

  7. Peanut Sensitization Burks AW. Lancet 2008;371,9623:1538-1546

  8. Development of Treatment Options • Allergen non-specific • Anti-IgE – not stand alone treatment • Leung, Sampson, et al. NEJM 2003; 348:986-93 • Chinese herbal medicine – in trials now Li, X 2003 J.AllergyClin.Immunol. 112:159-167 • Allergen-specific IgE binding • • • Engineered recombinant protein – reduced Oral immunotherapy (OIT) Sublingual immunotherapy (SLIT) Skripak Current Opinion In Immunology 2008,20:690-696

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

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

  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=.008 P=.001 * * Jones et al. -AAAAI 2010

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

  16. Serum Levels of Peanut-Specific IgE and IgG4 Change with Treatment 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 - 2010 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 of Immunotherapy • Oral IT (OIT) – swallowed with food • Sublingual IT (SLIT) – sublingually then swallowed • Differences – amount of protein, route?, digestion?, possibility of causing tolerance? SLIT OIT

  20. 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 Total home 4.6% 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% 3rd (3) study (CoFAR-NIH) 0% 0% - Adolescents and adults – 3 year study Upper Resp Skin 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 Peanut prick skin test DBPCFC

  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 300-4000 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 • 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/andclinical 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 • drbhaymore@gmail.com • www.allergyasthmacarecenters.com • 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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