Safety of Sublingual Immunotherapy (SLIT) for Peanut Allergy

Safety of Sublingual Immunotherapy (SLIT) for Peanut Allergy

S96 Abstracts 370 SUNDAY Safety of Sublingual Immunotherapy (SLIT) for Peanut Allergy S. S. Laubach1, P. Steele1, J. Kamilaris1, L. A. Pons1, M. Ku...

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S96 Abstracts

370

SUNDAY

Safety of Sublingual Immunotherapy (SLIT) for Peanut Allergy S. S. Laubach1, P. Steele1, J. Kamilaris1, L. A. Pons1, M. Kulis1, W. Schreffler2, A. W. Burks1; 1Duke University, Durham, NC, 2Mount Sinai Medical Center, New York City, NY. RATIONALE: Sublingual immunotherapy to induce tolerance to peanut would offer a novel treatment modality to help reduce the incidence of peanut-induced food reactions. METHODS: Pilot evaluation of SLIT in peanut-allergic subjects aged 6 to 35 years. Dosage escalation to a maintenance dose of 22 mcg/day of peanut protein (14% Ara h 1, 6% Ara h 2) was continued for 18 months. Subjects and their families completed daily home diaries. Immunologic laboratory studies were performed at 0, 3, 6, 12, and 18 months. RESULTS: Seven subjects have been enrolled in the initial cohort. Only two subjects had any allergic symptoms on the initial desensitization day. Three subjects experienced minimal allergic symptoms during the observed dose escalations. The home diary reports document 75 episodes of potentially allergic symptoms following approximately a total of 4070 home doses given (1.8%). The most common were sneezing, oral pruritus, and rhinorrhea (often associated with concurrent URI). IgE, IgG, and IgG4 levels and markers of basophil activation have not statistically changed over the first 12 months of SLIT. CONCLUSIONS: SLIT immunotherapy appears to be a well-tolerated form of peanut immunotherapy. Serum immunoglobulin levels have not changed significantly which correlates with observations of SLIT for inhaled allergens. Static immunoglobulin and basophil data may be due to the low maintenance dose and food challenges will clarify the significance. The initial results support the safety of SLIT to peanut protein and will be the basis for a larger, double-blind, placebo controlled study to evaluate the induction of tolerance in peanut allergic children. Funding: NIH

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Accidental Exposures (AE) to Peanut in Children with Peanut Allergy N. Nguyen Luu1, R. Kagan1, R. Alizadehfar1, M. Primeau1, M. BenShoshan1, L. Joseph1, N. Nicolas1, L. Harada2, C. Dufresne3, M. Allen4, E. Turnbull1, Y. St-Pierre1, A. Clarke1; 1McGill University Health Center, Montreal, PQ, CANADA, 2Anaphylaxis Canada, Toronto, ON, CANADA, 3Association que´be´coise des allergies alimentaires, Longueuil, PQ, CANADA, 4Allergy/Asthma Information Association, Vaughan, ON, CANADA. RATIONALE: Peanut avoidance is difficult and AE occur. We aimed to determine the incidence of AE in Canadian children with peanut allergy. METHODS: Children with a physician-confirmed diagnosis of peanut allergy were identified from: 1) the Montreal Children’s Hospital and 2) provincial and national food allergy advocacy organizations. Parents of participating children completed annual questionnaires regarding AE to peanut. RESULTS: Nine hundred seventy-one patients completed questionnaires at study entry and 271 at one year follow-up (only 350 were followed for one year post-entry and were eligible for the follow-up questionnaire). Mean age (SD) at diagnosis was 2.3 (2.0) years. One hundred forty-eight AE occurred in 127 children over 1178 patient-years, yielding an annual incidence rate of AE of 12.6% (95%CI, 10.6% to 14.8%). Fifty-nine reactions occurred at home, 27 at the homes of relatives, friends or neighbors, 13 in restaurants, 12 at school, including 9 in schools prohibiting peanut, 5 in daycare, and 32 at other or unknown places. Fifty-one reactions were mild (pruritus, urticaria, flushing and/or rhinoconjunctivitis), 78 were moderate (angioedema, voice change, coughing, nausea, vomiting and/or abdominal pain), and 19 were severe (wheezing, stridor, cyanosis and/or circulatory collapse). No treatment was administered for 13 mild and 13 moderate reactions. Epinephrine was used in only 22 of 97 moderate or severe reactions. CONCLUSIONS: Although increased awareness of peanut allergy in our cohort may have contributed to the lower rate of AE, most moderate and severe reactions were managed inappropriately. Therefore, better

J ALLERGY CLIN IMMUNOL FEBRUARY 2008

education of caregivers and patients regarding peanut allergy management is desirable. Funding: McGill University Health Center Foundation

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Indicators of Increased Risk for Peanut Sensitization/Likely Allergy among 3-15 Month Olds at Time of Entry to an Observational Study (CoFAR) of Food Allergy S. H. Sicherer1, D. Stablein2, S. Jones3, R. A. Wood4, A. W. Burks5, A. H. Liu6, D. M. Fleischer6, D. Y. M. Leung6, J. Ullah2, R. Lindblad2, H. A. Sampson1Consortium of Food Allergy Research1. 1Mount Sinai School of Medicine, New York, NY, 2The EMMES Corporation, Rockville, MD, 3Arkansas Children’s Hospital, Little Rock, AR, 4Johns Hopkins University School of Medicine, Baltimore, MD, 5Duke University Medical Center, Durham, NC, 6National Jewish Med. Res. Ctr., Denver, CO. RATIONALE: We observed a higher than expected rate (72%) of peanut (PN)-sensitization with 31% likely PN-allergic (PNA) (defined by PN-IgE > 5 kIU/ml) amongst subjects enrolled into an observational study of food allergy. Here we explore clinical-immunological factors relating to this observation. METHODS: Enrollment criteria were: ’’A’’- convincing clinical history of egg and/or milk allergy with a positive prick skin test to the trigger food AND/OR ’’B’’-moderate-severe atopic dermatitis (AD) and a positive milk or egg PST. Exclusion included known peanut allergy. Independent dichotomous variables included PN-IgE > 5 kIU/L or sensitization PN-PST  3 mm and/or PN-IgE > 0.34 kIU/L. RESULTS: 102/334 participants had PN-IgE > 5 kIU (35% males/22% females, p 5 0.02). PN-IgE > 5 was: not correlated with enrollment criteria ’’A’’ vs. ’’B,’’ age at enrollment, family income, maternal or paternal allergy history or being breast-fed; was variably associated with recall of peanut consumption during breastfeeding (less likely if consumed moderately compared to strict avoidance); and positively associated with AD score (p 5 .008), having both milk/egg allergy compared to either alone (p < .001), and recall of peanut ingestion during pregnancy (>23/wk 42% vs. infrequent 23%, p < 0.001). PN-IgE was strongly correlated with eggIgE (r 5 0.7, p <0.001). Analysis of PN-sensitization revealed similar trends and relationships to those of PN-IgE > 5 kIU/L. CONCLUSIONS: Factors associated with PN-sensitization/PN-IgE > 5 kIU/L on enrollment in this selected cohort included: AD severity, allergy to both egg and milk, elevated egg-IgE, and maternal recall of peanut ingestion during pregnancy; verification of clinical peanut allergy requires longitudinal evaluation. Funding: NIH-NIAID U19AI066738 and U01AI066560

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Sodium Bicarbonate Facilitates Low-dose Oral Tolerance To Peanut In Mice C. C. Bowman, M. K. Selgrade; USEPA, Research Triangle Park, NC. RATIONALE: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not peanut extract in mice. The current study objective was to determine the specific experimental parameters required to achieve oral tolerance to peanut. METHODS: Female C3H/HeJ mice were orally gavaged once with 1 or 2 mg of egg white or peanut extract in Hank’s balanced salt solution with or without 0.2M sodium bicarbonate one week prior to intraperitoneal immunization. Serum was collected one week later and assayed for egg or peanut specific antibody responses. RESULTS: IgE antibody responses were suppressed by prior oral exposure to egg white extract at all doses with or without sodium bicarbonate. Inhibition of IgE responses to peanut was demonstrated at the 2 mg dose but not at the 1 mg dose. However, addition of sodium bicarbonate for oral dosing led to induction of oral tolerance to peanut at both the 1 mg and 2 mg doses. CONCLUSIONS: Foods differ in their capacity to induce oral tolerance. In contrast to egg white, 1 mg of peanut given orally does not inhibit IgE production in mice unless it is administered in a 0.2M sodium bicarbonate