Peanut Oral Immunotherapy

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Peanut Oral Immunotherapy

• Pooja Varshney, MD
• Allergy/Immunology Fellow, Duke University
• School in Hypersensitivity Allergic Disease
• August 2008

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Background

• 1.1 of the total population is allergic to
  peanuts or tree nuts (Sicherer SH, Munoz-Furlong
  A, Sampson HA. JACI 2003)
• Peanuts and tree nuts are responsible for the
  majority of severe and fatal anaphylactic
  reactions to food (Sampson HA. JACI 2001)
• Peanut allergy resolves for 20 of children by
  school age (Skolnick HS, Sampson HA, Burks W,
  Wood RA. JACI 2001)
• Current treatment options are strict avoidance of
  peanut and access to self-injectable epinephrine

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Background

• Pilot peanut OIT study 20 patients completed
  treatment
• Open challenge to peanut - 19/20 ingested 3900 mg
  of peanut protein.
• Significant increase in the threshold of peanut
  needed to cause allergic symptoms compared to the
  initial escalation day

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Pilot OIT Study
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Pilot OIT Study
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Questions

• Why did subjects pass an open peanut challenge at
  the end of the study?
• What is the mechanism of action of peanut oral
  immunotherapy (OIT)?
• Can peanut OIT induce a state of immunologic
  tolerance?

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Hypothesis

• 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.

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Study Objectives

• 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
• Objective 2 To determine the molecular-level
  effect that peanut OIT has on peanut-specific
  cellular and humoral responses in peanut-allergic
  subjects

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Study Protocol
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Study Protocol
36 months 10 gm OFC
Maintenance dose 4 gm or highest achieved dose
Randomization
If peanut IgE lt 2, OFC 4 weeks after stopping OIT
Treatment
5 gm OFC 4 weeks after reaching maint OIT dose
24 months 10 gm OFC
Initial escalation day Up-dosing week 1-46
Enrollment
Placebo
Cross-over to 36 mo treatment arm
Blinded portion of study ends
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Study Endpoints

• Primary Endpoint
• Percentage of subjects who can tolerate 10 gm of
  peanut protein 4 weeks after discontinuing peanut
  OIT
• Secondary Endpoints
• Percentage who pass the 5 gm peanut protein OFC
  following the desensitization phase of the study
• Percentage who tolerate the initial-day
  escalation to 6 mg of peanut protein
• Percentage who achieve the 4 gm maintenance dose
  of peanut protein OIT during the desensitization
  phase of the study
• Incidence of all serious adverse events during
  the study

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Immune Responses

• Cellular proliferation response to Ara h 2, crude
  peanut extract, ConA
• Antigen-specific cytokine production
• Changes in T regulatory cells over time
• Basophil responsiveness
• Peanut-specific IgE, IgG, IgG4
• Facilitated antigen binding
• Specific salivary S-IgA

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Preliminary Results

• 5 blinded peanut OFCs completed after 12 months
  on treatment or placebo
• 3 subjects on treatment OIT successfully ingested
  5 grams peanut protein
• 2 patients on placebo reacted after ingesting 50
  mg and 250 mg of peanut protein, respectively

Blinded portion of study ends
Cross over to 36 month treatment arm
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Preliminary Results

• Secondary Endpoints
• Percentage who pass the 5 gm peanut protein OFC
  following the desensitization phase of the study
  ? 3/3
• Percentage who tolerate the initial-day
  escalation to 6 mg of peanut protein ? all
• Percentage who achieve the 4 gm maintenance dose
  of peanut protein OIT during the desensitization
  phase of the study ? all
• Incidence of all serious adverse events during
  the study ? epinephrine given to one subject
  receiving placebo

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My part

• Reviewing IRB
• Enrolling subjects
• Supervising initial escalation day and challenges
• Preparing databases
• Analyzing clinical and laboratory data

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Future

• 24- or 36-month DBPCFC
• Evaluate desensitization
• DBPCFC 4 weeks after stopping OIT
• Evaluate tolerance mechanisms
• Define the relationship between clinical response
  and immunologic makers of tolerance induction

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Research Team

• Duke University
• A. Wesley Burks, Susan S. Laubach, Drew Bird,
  Ananth Thyagarajan, Margaret Ann Adair, Pamela
  Steele, Janet Kamilaris, Alison Edie, Laurent
  Pons, Michael Kulis
• University of Arkansas
• Stacie M. Jones, Amy M. Scurlock, KA Althage, S
  Carlisle, L Christie