Peanut Oral Immunotherapy Pooja Varshney, MD Allergy/Immunology Fellow, Duke University School in Hypersensitivity & Aller...
Background <ul><li>1.1% of the total population is allergic to peanuts or tree nuts (Sicherer SH, Munoz-Furlong A, Sampso...
Background <ul><li>Pilot peanut OIT study – 20 patients completed treatment </li></ul><ul><li>Open challenge to peanut - ...
Pilot OIT Study
Pilot OIT Study
Questions <ul><li>Why did subjects pass an open peanut challenge at the end of the study? </li></ul><ul><li>What is the me...
Hypothesis <ul><li>Peanut oral immunotherapy will induce a state of clinical tolerance over time and stimulate changes in ...
Study Objectives <ul><li>Objective #1: To treat peanut-allergic subjects with peanut OIT and to determine whether this pr...
Study Protocol Randomized, blinded placebo-controlled study Peanut OIT n = 20 Placebo n = 10 Controls n = 30 Peanut flour ...
Study Protocol Enrollment Randomization Treatment Placebo Maintenance dose 4 gm or highest achieved dose 5 gm OFC 4 weeks ...
Study Endpoints <ul><li>Primary Endpoint </li></ul><ul><ul><li>Percentage of subjects who can tolerate 10 gm of peanut pro...
Immune Responses <ul><li>Cellular proliferation response to Ara h 2 , crude peanut extract, ConA </li></ul><ul><li>Antige...
Preliminary Results <ul><li>5 blinded peanut OFCs completed after ~12 months on treatment or placebo </li></ul><ul><ul><li...
Preliminary Results <ul><li>Secondary Endpoints </li></ul><ul><ul><li>Percentage who pass the 5 gm peanut protein OFC fol...
My part <ul><li>Reviewing IRB </li></ul><ul><li>Enrolling subjects </li></ul><ul><li>Supervising initial escalation day a...
Future <ul><li>24- or 36-month DBPCFC </li></ul><ul><ul><li>Evaluate desensitization </li></ul></ul><ul><li>DBPCFC 4 weeks...
Research Team <ul><li>Duke University </li></ul><ul><li>A. Wesley Burks, Susan S. Laubach, Drew Bird, Ananth Thyagarajan, ...
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Pooja Varshney, MD

Published on: Mar 4, 2016
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Transcripts - Pooja Varshney, MD

  • 1. Peanut Oral Immunotherapy Pooja Varshney, MD Allergy/Immunology Fellow, Duke University School in Hypersensitivity & Allergic Disease August 2008
  • 2. Background <ul><li>1.1% of the total population is allergic to peanuts or tree nuts (Sicherer SH, Munoz-Furlong A, Sampson HA. JACI 2003) </li></ul><ul><li>Peanuts and tree nuts are responsible for the majority of severe and fatal anaphylactic reactions to food (Sampson HA. JACI 2001) </li></ul><ul><li>Peanut allergy resolves for ~20% of children by school age (Skolnick HS, Sampson HA, Burks W, Wood RA. JACI 2001) </li></ul><ul><li>Current treatment options are strict avoidance of peanut and access to self-injectable epinephrine </li></ul>
  • 3. Background <ul><li>Pilot peanut OIT study – 20 patients completed treatment </li></ul><ul><li>Open challenge to peanut - 19/20 ingested 3900 mg of peanut protein. </li></ul><ul><li>Significant increase in the threshold of peanut needed to cause allergic symptoms compared to the initial escalation day </li></ul>
  • 4. Pilot OIT Study
  • 5. Pilot OIT Study
  • 6. Questions <ul><li>Why did subjects pass an open peanut challenge at the end of the study? </li></ul><ul><li>What is the mechanism of action of peanut oral immunotherapy (OIT)? </li></ul><ul><li>Can peanut OIT induce a state of immunologic tolerance? </li></ul>
  • 7. Hypothesis <ul><li>Peanut oral immunotherapy will induce a state of clinical tolerance over time and stimulate changes in the cellular and humoral immune system of subjects with peanut allergy. </li></ul>
  • 8. Study Objectives <ul><li>Objective #1: To treat peanut-allergic subjects with peanut OIT and to determine whether this protocol lowers their risk of allergic reactions (desensitization) and causes long-term tolerance </li></ul><ul><li>Objective #2: To determine the molecular-level effect that peanut OIT has on peanut-specific cellular and humoral responses in peanut-allergic subjects </li></ul>
  • 9. Study Protocol Randomized, blinded placebo-controlled study Peanut OIT n = 20 Placebo n = 10 Controls n = 30 Peanut flour (50% peanut protein) No study product Oat flour Age 1-6 years Positive SPT Peanut IgE>7 Clinical hx
  • 10. Study Protocol Enrollment Randomization Treatment Placebo Maintenance dose 4 gm or highest achieved dose 5 gm OFC 4 weeks after reaching maint OIT dose Blinded portion of study ends Cross-over to 36 mo treatment arm 24 months 10 gm OFC 36 months 10 gm OFC If peanut IgE < 2, OFC 4 weeks after stopping OIT Initial escalation day Up-dosing week 1-46+
  • 11. Study Endpoints <ul><li>Primary Endpoint </li></ul><ul><ul><li>Percentage of subjects who can tolerate 10 gm of peanut protein 4 weeks after discontinuing peanut OIT </li></ul></ul><ul><li>Secondary Endpoints </li></ul><ul><ul><li>Percentage who pass the 5 gm peanut protein OFC following the desensitization phase of the study </li></ul></ul><ul><ul><li>Percentage who tolerate the initial-day escalation to 6 mg of peanut protein </li></ul></ul><ul><ul><li>Percentage who achieve the 4 gm maintenance dose of peanut protein OIT during the desensitization phase of the study </li></ul></ul><ul><ul><li>Incidence of all serious adverse events during the study </li></ul></ul>
  • 12. Immune Responses <ul><li>Cellular proliferation response to Ara h 2 , crude peanut extract, ConA </li></ul><ul><li>Antigen-specific cytokine production </li></ul><ul><li>Changes in T regulatory cells over time </li></ul><ul><li>Basophil responsiveness </li></ul><ul><li>Peanut-specific IgE, IgG, IgG 4 </li></ul><ul><li>Facilitated antigen binding </li></ul><ul><li>Specific salivary S-IgA </li></ul>
  • 13. Preliminary Results <ul><li>5 blinded peanut OFCs completed after ~12 months on treatment or placebo </li></ul><ul><ul><li>3 subjects on treatment OIT successfully ingested 5 grams peanut protein </li></ul></ul><ul><ul><li>2 patients on placebo reacted after ingesting 50 mg and 250 mg of peanut protein, respectively </li></ul></ul>Blinded portion of study ends Cross over to 36 month treatment arm
  • 14. Preliminary Results <ul><li>Secondary Endpoints </li></ul><ul><ul><li>Percentage who pass the 5 gm peanut protein OFC following the desensitization phase of the study  3/3 </li></ul></ul><ul><ul><li>Percentage who tolerate the initial-day escalation to 6 mg of peanut protein  all </li></ul></ul><ul><ul><li>Percentage who achieve the 4 gm maintenance dose of peanut protein OIT during the desensitization phase of the study  all </li></ul></ul><ul><ul><li>Incidence of all serious adverse events during the study  epinephrine given to one subject receiving placebo </li></ul></ul>
  • 15. My part <ul><li>Reviewing IRB </li></ul><ul><li>Enrolling subjects </li></ul><ul><li>Supervising initial escalation day and challenges </li></ul><ul><li>Preparing databases </li></ul><ul><li>Analyzing clinical and laboratory data </li></ul>
  • 16. Future <ul><li>24- or 36-month DBPCFC </li></ul><ul><ul><li>Evaluate desensitization </li></ul></ul><ul><li>DBPCFC 4 weeks after stopping OIT </li></ul><ul><ul><li>Evaluate tolerance mechanisms </li></ul></ul><ul><li>Define the relationship between clinical response and immunologic makers of tolerance induction </li></ul>
  • 17. Research Team <ul><li>Duke University </li></ul><ul><li>A. Wesley Burks, Susan S. Laubach, Drew Bird, Ananth Thyagarajan, Margaret Ann Adair, Pamela Steele, Janet Kamilaris, Alison Edie, Laurent Pons, Michael Kulis </li></ul><ul><li>University of Arkansas </li></ul><ul><li>Stacie M. Jones, Amy M. Scurlock, KA Althage, S Carlisle, L Christie </li></ul>

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