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Omalizumab In Peanut-allergic Patients Reduces Free IgE anti-Peanut And Skin Prick Tests To Peanut
AB22 Abstracts
SATURDAY
84
Induction Of Tolerance Through Early Introduction Of Peanut In High-Risk Children, The LEAP Study G. Du Toit1, G. Roberts2, P. Sayre3, V. Turcanu1, H. R. Fisher1, D. Broide4, L. Nirenstein1, S. Radulovic1, A. Stephens1, V. Seyfert-Margolis3, N. Nasser3, S. Murphy. The LEAP Study Group. The Immune Tolerance Network ITN032AD Study Group5,1,3, G. Lack1; 1King’s College London. MRC & Asthma UK Centre in Allergic Mechanisms of Asthma. Division of Asthma, Allergy and Lung Biology. Guy’s and St ThomasÕ NHS Foundation Trust, London, UNITED KINGDOM, 2Southampton University Hospital NHS Trust, Southampton, UK, London, UNITED KINGDOM, 3 Immune Tolerance Network, UCSF, San Fransisco, CA, 4University of California, San Diego, CA, 5Biostatistics, Rho, Inc, Chapel Hill, NC. RATIONALE: To compare peanut-avoidance and early peanut-consumption as interventions for the prevention of peanut allergy (PA) within a randomised controlled trial. METHODS: This randomised control group study aimed to recruit 640 high-risk infants aged 4-11 months. High risk was defined as severe eczema and/or egg allergy. The 640 participants were to be stratified by peanut skin prick tests (SPT) results into one of two Strata; SPT-Negative Stratum (n5542) or the SPT-Positive Stratum (SPT 1-4mm, n598). Participants were then randomly assigned to receive early high-dose peanut, or to complete peanut avoidance. The primary endpoint is the prevalence of clinically-defined PA between the two groups at 60 months of age. Secondary endpoints include allergic sensitization to select ingested and inhaled allergens, rhinoconjunctivitis and asthma. Analyses of Cellular and Humoral responses will be performed. RESULTS: Nine hundred participants were screened of which 640 were eligible for enrolment (98 assigned to the SPT-positive Stratum and 542 to the SPT-Negative Stratum). Demographics at enrolment: age (median 7.8 months, range 4-11), male (60%), ethnicity (Caucasian 74%, Mixed 14%, Black 8%, Asian 4%). 89.1% of participants met the study criteria for Severe Eczema and 65.3% of participants met the study definition of Egg Allergy; 52.0% met both criteria. None of the participants had consumed peanut prior to enrolment. CONCLUSIONS: Enrolment of 640 high-risk infants into the LEAP Study has now successfully completed. It is hoped that the comparison between these two approaches, to be made at 60 months of age, will identify the best strategy for the prevention of peanut allergy.
85
Impact of Oral Food-Specific Immunotheraphy (OIT) on Health Related Quality of Life (HRQL) of Children and Parents During Build Up of Tolerance A. Bird1, D. Daly2, W. Burks3, J. O. B. Hourihane2, A. DunnGalvin2; 1UT Southwestern Medical Center, Dallas, TX, 2University College Cork, Cork, IRELAND, 3Duke University, Durham, NC. RATIONALE: Oral food-specific immunotherapy (OIT) is a novel treatment strategy currently under investigation. We assessed the impact of experimental OIT on the HRQL of children and parents during build up of tolerance. METHODS: Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF) was completed before starting a placebo-controlled OIT research protocol and at the 2nd, 3rd, 4th or 5th clinic visit. Change was analysed using a repeated measures multivariate design. Reliability of the change score was computed as an intraclass correlation coefficient (ICC) of change. The minimally important difference (MID) was determined using distributional criteria and global scores. Open questions on motivation for taking part were qualitatively analysed. RESULTS: Most children (N524; M5 5 yrs) were on the 3rd clinic visit (54%). Parentally assessed HRQL improved significantly from baseline to the 3rd visit (p<.05). The majority of parents (85%) were Ôvery satisfiedÕ with the conduct of treatment, and information provided to parents and child. Although the magnitude differed, HRQL improved both for those who perceived OIT Ôto be workingÕ (70%) and Ônot workingÕ. MID was 0.51 on a 7-point response scale. ICC was 0.90. Qualitative analyses showed different motivating factors in parents (uncertainty anxiety and guilt) and children (psychosocial limitations).
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
CONCLUSIONS: Undergoing OIT appears to have a positive impact on HRQL, irrespective of whether parents perceive the treatment to be effective, because specific concerns are addressed by expert care. This study effect has significance for other novel treatments both for food allergy and for other unrelated conditions.
86
Persistence of Tolerance After Specific Oral Tolerance Induction M. Rodrı´guez-Alvarez, M. Fernandez-Rivas, T. Robledo Echarren, C. Martinez-Co´cera; Hospital Clinico San Carlos, Madrid, SPAIN. RATIONALE: Little is known about tolerance after treatment with specific oral tolerance induction (SOTI). We have developed a new protocol for SOTI in patients with persistent cow’s milk allergy and in this study we analysed the persistence of tolerance after one and two years of follow up. METHODS: Twenty five patients older than 4 years with persistent cow’s milk allergy confirmed by a double-blind-placebo-control- food challenge test were recruited to participate in our study. All patients achieved tolerance to 200ml. Total IgE, skin prick test (SPT), specific IgE and IgG4 to cow’s milk (CM), casein, alphalactalbumin (ALA) and betalactoglobulin (BLG) were performed at the baseline and after each year of follow up in all patients. After one and two years of follow up patients were evaluated to assess whether tolerance was maintained. RESULTS: A decrease on mean of SPT to milk and milk proteins, specific IgE to CM and Casein and increase on specific IgG4 to milk and casein were observed when baseline values were compared to one year of follow up data. (p<0.05) (statistical analysis was made by a paired Wilcoxon test). Nowadays we have results of one year of follow up in all patients and two years of follow up in 13 patients and tolerance was maintained in all of them. CONCLUSIONS: Immunological changes after SOTI are similar to the ones described after specific immunotherapy that could be a marker of persistent tolerance. Our results suggest that SOTI is an effective treatment option for persistent cow’s milk allergy.
87
Omalizumab In Peanut-allergic Patients Reduces Free IgE antiPeanut And Skin Prick Tests To Peanut G. P. Yu1, K. S. Tuano1, R. G. Hamilton2, K. C. Nadeau1; 1Stanford University School of Medicine, Palo Alto, CA, 2Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Omalizumab treatment in peanut allergic patients can decrease the threshold of reactivity to peanut. However, not all patients respond to Omalizumab treatment. We hypothesized that decreased free IgE to peanut and negative skin prick test to peanut on Omalizumab would predict the ability to pass a double-blind, placebo-controlled food challenge (DBPCFC) to peanut. METHODS: 5 subjects (ages 5-25 years) with positive clinical history and a peanut skin prick test (SPT) 8mm wheal or peanut-specific IgE 15kUa/L (ImmunoCAP, Phadia) were enrolled. Omalizumab was dosed per product insert every 2-4 weeks. Free IgE anti-peanut was computed from the total IgE anti-peanut and the Free/Total IgE percentage in sera post Omalizumab dosing. Once free IgE anti-peanut decreased to <15kUa/L, titrated SPT with peanut extract (Hollister-Stier) was performed. If peanut SPT was negative, a DBPCFC was performed to peanut and rice flour. RESULTS: Free IgE anti-peanut decreased from a mean of 119.4 kUa/L (range 6.2-456.1 kUa/L) to 5.9 kUa/L (range 1.5-10.7 kUa/L) within 412 weeks of Omalizumab dosing. One of 5 subjects developed a negative peanut SPT at 4 weeks. This subject, with a history of angioedema, urticaria, and wheezing upon peanut ingestion underwent a DBPCFC and tolerated 5 grams of peanut flour. CONCLUSIONS: Decreasing Free IgE anti-peanut to <15kUa/L and developing a negative peanut SPT following Omalizumab administration may allow one to predict the ability to pass a DBPCFC to peanut. However, the sample size is small and larger studies are needed to confirm these findings.
SATURDAY
84
Induction Of Tolerance Through Early Introduction Of Peanut In High-Risk Children, The LEAP Study G. Du Toit1, G. Roberts2, P. Sayre3, V. Turcanu1, H. R. Fisher1, D. Broide4, L. Nirenstein1, S. Radulovic1, A. Stephens1, V. Seyfert-Margolis3, N. Nasser3, S. Murphy. The LEAP Study Group. The Immune Tolerance Network ITN032AD Study Group5,1,3, G. Lack1; 1King’s College London. MRC & Asthma UK Centre in Allergic Mechanisms of Asthma. Division of Asthma, Allergy and Lung Biology. Guy’s and St ThomasÕ NHS Foundation Trust, London, UNITED KINGDOM, 2Southampton University Hospital NHS Trust, Southampton, UK, London, UNITED KINGDOM, 3 Immune Tolerance Network, UCSF, San Fransisco, CA, 4University of California, San Diego, CA, 5Biostatistics, Rho, Inc, Chapel Hill, NC. RATIONALE: To compare peanut-avoidance and early peanut-consumption as interventions for the prevention of peanut allergy (PA) within a randomised controlled trial. METHODS: This randomised control group study aimed to recruit 640 high-risk infants aged 4-11 months. High risk was defined as severe eczema and/or egg allergy. The 640 participants were to be stratified by peanut skin prick tests (SPT) results into one of two Strata; SPT-Negative Stratum (n5542) or the SPT-Positive Stratum (SPT 1-4mm, n598). Participants were then randomly assigned to receive early high-dose peanut, or to complete peanut avoidance. The primary endpoint is the prevalence of clinically-defined PA between the two groups at 60 months of age. Secondary endpoints include allergic sensitization to select ingested and inhaled allergens, rhinoconjunctivitis and asthma. Analyses of Cellular and Humoral responses will be performed. RESULTS: Nine hundred participants were screened of which 640 were eligible for enrolment (98 assigned to the SPT-positive Stratum and 542 to the SPT-Negative Stratum). Demographics at enrolment: age (median 7.8 months, range 4-11), male (60%), ethnicity (Caucasian 74%, Mixed 14%, Black 8%, Asian 4%). 89.1% of participants met the study criteria for Severe Eczema and 65.3% of participants met the study definition of Egg Allergy; 52.0% met both criteria. None of the participants had consumed peanut prior to enrolment. CONCLUSIONS: Enrolment of 640 high-risk infants into the LEAP Study has now successfully completed. It is hoped that the comparison between these two approaches, to be made at 60 months of age, will identify the best strategy for the prevention of peanut allergy.
85
Impact of Oral Food-Specific Immunotheraphy (OIT) on Health Related Quality of Life (HRQL) of Children and Parents During Build Up of Tolerance A. Bird1, D. Daly2, W. Burks3, J. O. B. Hourihane2, A. DunnGalvin2; 1UT Southwestern Medical Center, Dallas, TX, 2University College Cork, Cork, IRELAND, 3Duke University, Durham, NC. RATIONALE: Oral food-specific immunotherapy (OIT) is a novel treatment strategy currently under investigation. We assessed the impact of experimental OIT on the HRQL of children and parents during build up of tolerance. METHODS: Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF) was completed before starting a placebo-controlled OIT research protocol and at the 2nd, 3rd, 4th or 5th clinic visit. Change was analysed using a repeated measures multivariate design. Reliability of the change score was computed as an intraclass correlation coefficient (ICC) of change. The minimally important difference (MID) was determined using distributional criteria and global scores. Open questions on motivation for taking part were qualitatively analysed. RESULTS: Most children (N524; M5 5 yrs) were on the 3rd clinic visit (54%). Parentally assessed HRQL improved significantly from baseline to the 3rd visit (p<.05). The majority of parents (85%) were Ôvery satisfiedÕ with the conduct of treatment, and information provided to parents and child. Although the magnitude differed, HRQL improved both for those who perceived OIT Ôto be workingÕ (70%) and Ônot workingÕ. MID was 0.51 on a 7-point response scale. ICC was 0.90. Qualitative analyses showed different motivating factors in parents (uncertainty anxiety and guilt) and children (psychosocial limitations).
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
CONCLUSIONS: Undergoing OIT appears to have a positive impact on HRQL, irrespective of whether parents perceive the treatment to be effective, because specific concerns are addressed by expert care. This study effect has significance for other novel treatments both for food allergy and for other unrelated conditions.
86
Persistence of Tolerance After Specific Oral Tolerance Induction M. Rodrı´guez-Alvarez, M. Fernandez-Rivas, T. Robledo Echarren, C. Martinez-Co´cera; Hospital Clinico San Carlos, Madrid, SPAIN. RATIONALE: Little is known about tolerance after treatment with specific oral tolerance induction (SOTI). We have developed a new protocol for SOTI in patients with persistent cow’s milk allergy and in this study we analysed the persistence of tolerance after one and two years of follow up. METHODS: Twenty five patients older than 4 years with persistent cow’s milk allergy confirmed by a double-blind-placebo-control- food challenge test were recruited to participate in our study. All patients achieved tolerance to 200ml. Total IgE, skin prick test (SPT), specific IgE and IgG4 to cow’s milk (CM), casein, alphalactalbumin (ALA) and betalactoglobulin (BLG) were performed at the baseline and after each year of follow up in all patients. After one and two years of follow up patients were evaluated to assess whether tolerance was maintained. RESULTS: A decrease on mean of SPT to milk and milk proteins, specific IgE to CM and Casein and increase on specific IgG4 to milk and casein were observed when baseline values were compared to one year of follow up data. (p<0.05) (statistical analysis was made by a paired Wilcoxon test). Nowadays we have results of one year of follow up in all patients and two years of follow up in 13 patients and tolerance was maintained in all of them. CONCLUSIONS: Immunological changes after SOTI are similar to the ones described after specific immunotherapy that could be a marker of persistent tolerance. Our results suggest that SOTI is an effective treatment option for persistent cow’s milk allergy.
87
Omalizumab In Peanut-allergic Patients Reduces Free IgE antiPeanut And Skin Prick Tests To Peanut G. P. Yu1, K. S. Tuano1, R. G. Hamilton2, K. C. Nadeau1; 1Stanford University School of Medicine, Palo Alto, CA, 2Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Omalizumab treatment in peanut allergic patients can decrease the threshold of reactivity to peanut. However, not all patients respond to Omalizumab treatment. We hypothesized that decreased free IgE to peanut and negative skin prick test to peanut on Omalizumab would predict the ability to pass a double-blind, placebo-controlled food challenge (DBPCFC) to peanut. METHODS: 5 subjects (ages 5-25 years) with positive clinical history and a peanut skin prick test (SPT) 8mm wheal or peanut-specific IgE 15kUa/L (ImmunoCAP, Phadia) were enrolled. Omalizumab was dosed per product insert every 2-4 weeks. Free IgE anti-peanut was computed from the total IgE anti-peanut and the Free/Total IgE percentage in sera post Omalizumab dosing. Once free IgE anti-peanut decreased to <15kUa/L, titrated SPT with peanut extract (Hollister-Stier) was performed. If peanut SPT was negative, a DBPCFC was performed to peanut and rice flour. RESULTS: Free IgE anti-peanut decreased from a mean of 119.4 kUa/L (range 6.2-456.1 kUa/L) to 5.9 kUa/L (range 1.5-10.7 kUa/L) within 412 weeks of Omalizumab dosing. One of 5 subjects developed a negative peanut SPT at 4 weeks. This subject, with a history of angioedema, urticaria, and wheezing upon peanut ingestion underwent a DBPCFC and tolerated 5 grams of peanut flour. CONCLUSIONS: Decreasing Free IgE anti-peanut to <15kUa/L and developing a negative peanut SPT following Omalizumab administration may allow one to predict the ability to pass a DBPCFC to peanut. However, the sample size is small and larger studies are needed to confirm these findings.