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A Prospective, Randomized, Case Controlled Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated with Peanut Desensitization in Children with Peanut Allergies
AB28 Abstracts
SATURDAY
105
Peanut Oral Immunotherapy and Omalizumab Treatment for Peanut Allergy M. Henson, A. Edie, P. Steele, J. Kamilaris, M. Kulis, A. Thyagarajan, B. P. Vickery, A. W. Burks; Duke University School of Medicine, Durham, NC. RATIONALE: We hypothesize that treatment with omalizumab prior to starting oral immunotherapy (OIT) will reduce symptoms, allowing acceleration of the build-up phase and achievement of maintenance dosing more quickly. METHODS: Peanut-allergic patients aged 12 years and older were enrolled in this study. Omalizumab was given for 4 months prior to initiation of OIT, followed by a modified rush day(s), a build-up period, and a daily home maintenance phase with a final dose of 4000 mg of peanut protein. Omalizumab was continued for one month after reaching maintenance dosing. RESULTS: 6 patients had evaluable safety data. The median peanutspecific IgE in this group was 68.7 kU/L. The median total IgE was 486.5 kU/L. 6/6 patients experienced symptoms on the rush desensitization days with 20/21 symptoms graded as mild, primarily respiratory in nature, comparable to previously published safety data for rush desensitization without omalizumab. The median peanut starting dose after rush desensitization with omalizumab was 300 mg (range 100-400), higher than that seen without omalizumab pretreatment. On dose escalation days, 9.5% of doses (6 of 63) resulted in symptoms in the omalizumab group, in contrast to 43.3% of doses (123 of 284) resulting in symptoms in previous studies [RR 0.22 (95%CI 0.10-0.48), p<0.0001]. CONCLUSION: These results, although limited by small sample sizes, suggest that omalizumab therapy has the potential to reduce side effects during dose escalation and allow a higher starting dose of peanut. This may enhance safety and allow patients to reach maintenance dosing sooner than in previous peanut OIT trials. Funding: NIH-NIAID & Novartis.
106
Measurement of the Eliciting Dose Threshold at Baseline is Useful for Establishing the Starting Dose in Peanut Oral Immunotherapy (OIT) J. A. Bird1, A. Clark2, M. G. Crain2, A. Arneson2; 1UT Southwestern Medical Center, Dallas, TX, 2Children’s Medical Center, Dallas, TX. RATIONALE: The majority of peanut OIT trials to date have initiated therapy with a standard dose of peanut flour. We hypothesized that by initiating therapy at a dose proportional to the eliciting threshold dose measured at entry challenge, subjects would be able to safely start at an accelerated dose. _ 7 kU/L METHODS: Subjects with ImmunoCAP peanut-specific IgE > _ 3mm underwent a and peanut skin prick test (SPT) wheal diameter > double-blind placebo-controlled food challenge (DBPCFC) to peanut. Those who reacted during the DBPCFC returned to receive peanut OIT with lightly roasted peanut flour. For subjects tolerating a cumulative dose of > 75mg of protein, the starting dose of therapy was initiated at 2 dosing increments below the highest single tolerated dose based on the build-up protocol. Subjects returned for dose escalation bi-weekly. RESULTS: Eleven of twelve subjects (ages 5 - 16 years) reacted to peanut during the DBPCFC, and 9/12 subjects tolerated > 75mg of protein. For the remaining 8 subjects, reaction-eliciting doses ranged from 75 to 250mg (median 112.5mg) of protein. Therapy was initiated between 12.5 and 150mg of protein (median 37.5mg). During dose escalation, 1 subject had 2 severe reactions precipitated by: (1.) taking a hot shower within 2 hours of the dose, and (2.) taking dose on an empty stomach. All other subjects complained of only mild symptoms, similar to reports from previous trials. CONCLUSION: Consideration for an individualized starting dose based on the eliciting dose threshold appears to safely accelerate the dosing schedule for subjects receiving peanut OIT.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
107
A Prospective, Randomized, Case Controlled Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated with Peanut Desensitization in Children with Peanut Allergies N. Berlin1, S. Maclachlan1, N. Leader1, D. Penn2, G. Sussman1,3; 1 Gordon Sussman Clinical Research Inc., Toronto, ON, CANADA, 2 Mast Cell Pharmaceuticals Inc., Raleigh, NC, 3University of Toronto, Toronto, ON, CANADA. RATIONALE: To decrease allergic reactions during oral peanut desensitization we studied the effect of premedication with ketotifen, an anti allergenic used to treat ocular allergy and allergic asthma. METHODS: 6 Patients (4M:2F) with prior histories of peanut anaphylaxis (grade 2 and specific IgE > 100) were enrolled in a single blind placebo controlled study, with escalating doses of ketotifen pretreatment of up to 4mg. A rush oral peanut desensitization protocol was used according to previous published studies, up to 50mg peanut flour (z25mg protein) on day-1, followed by a biweekly schedule of escalating doses. Ketotifen continued after day-1. RESULTS: All moderate to severe reactions (10) occurred in placebo patients and were gastrointestinal (abdominal cramps, nausea, vomiting, diarrhea). The overall day-1 reaction rate was 18.5% and all reactions occurred between the 3mg and 50mg doses. The overall reaction rate for the following 2 weeks was 38% (26% in treatment and 72% in placebo). 3 anaphylactic reactions occurred: day-1 placebo patient at 50mg dose (gastrointestinal, cutaneous); day-5 treatment patient at 50mg dose, occurred post exercise, (gastrointestinal, cutaneous, respiratory); day-6 placebo patient at 12mg dose, associated with fever, (gastrointestinal, cutaneous, respiratory), epinephrine was given and patient withdrew from study. Eosinophil counts were elevated for all patients upon 2nd visit, and decreased over time. CONCLUSIONS: Pretreatment with ketotifen 4mg greatly decreases side effects associated with the desensitization procedure, most of which were gastrointestinal. Eosinophilia was observed in all patients after day-1. We suspect that anti-inflammatory gastrointestinal cytoprotection may be the mechanism of action of ketotifen.
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Oral Food Immunotherapy: Protective Doses Reached Within Two Months M. B. Levy, M. R. Goldberg, M. L. Stein, A. Elizur, L. Nachshon, Y. Katz; Assaf Harofe Medical Center, Tzrifin, ISRAEL. RATIONALE: Oral food immunotherapy (OFI) has been shown to be efficacious. Protocols vary as to the amount of time needed to reach doses that may be protective of an accidental product ingestion. METHODS: The clinical records of 252 patients enrolled in an active OFI program for milk, peanut and egg protein were reviewed. This individualized dose escalation protocol includes a 4 day induction-desensitization phase performed in a hospital based out-patient clinic where a maximal individualized tolerated dose (MITD) is determined. The MITD is consumed twice daily at home for 24 days and the cycle repeated. RESULTS: Patients ranged in age from 4-27 years (average 8.5 years). 152 (60%) were male. 125/252 (49.6%) had a history of asthma. Treatment groups included 235 milk, 12 peanut, and 5 egg patients. After completing at least three dose escalation sessions over two months, 178/208 (85%) of milk allergy patients were able to consume 180 mg or more, an amount considered to be protective for an accidental dairy contaminated product ingestion. After three sessions 6/8 (75%) of peanut patients were able to consume 300 mg or more, the protein equivalent of one peanut, and 2/4 (50%) of egg patients were able to consume 1500 mg or more, the protein equivalent of 1/4 of an egg. Treatment failures totaled 24/235 (9.5%). CONCLUSIONS: Using the current oral food immunotherapy protocol, the majority of milk, peanut and egg allergic patients are able to achieve a protective dose of allergenic protein within two months of treatment.
SATURDAY
105
Peanut Oral Immunotherapy and Omalizumab Treatment for Peanut Allergy M. Henson, A. Edie, P. Steele, J. Kamilaris, M. Kulis, A. Thyagarajan, B. P. Vickery, A. W. Burks; Duke University School of Medicine, Durham, NC. RATIONALE: We hypothesize that treatment with omalizumab prior to starting oral immunotherapy (OIT) will reduce symptoms, allowing acceleration of the build-up phase and achievement of maintenance dosing more quickly. METHODS: Peanut-allergic patients aged 12 years and older were enrolled in this study. Omalizumab was given for 4 months prior to initiation of OIT, followed by a modified rush day(s), a build-up period, and a daily home maintenance phase with a final dose of 4000 mg of peanut protein. Omalizumab was continued for one month after reaching maintenance dosing. RESULTS: 6 patients had evaluable safety data. The median peanutspecific IgE in this group was 68.7 kU/L. The median total IgE was 486.5 kU/L. 6/6 patients experienced symptoms on the rush desensitization days with 20/21 symptoms graded as mild, primarily respiratory in nature, comparable to previously published safety data for rush desensitization without omalizumab. The median peanut starting dose after rush desensitization with omalizumab was 300 mg (range 100-400), higher than that seen without omalizumab pretreatment. On dose escalation days, 9.5% of doses (6 of 63) resulted in symptoms in the omalizumab group, in contrast to 43.3% of doses (123 of 284) resulting in symptoms in previous studies [RR 0.22 (95%CI 0.10-0.48), p<0.0001]. CONCLUSION: These results, although limited by small sample sizes, suggest that omalizumab therapy has the potential to reduce side effects during dose escalation and allow a higher starting dose of peanut. This may enhance safety and allow patients to reach maintenance dosing sooner than in previous peanut OIT trials. Funding: NIH-NIAID & Novartis.
106
Measurement of the Eliciting Dose Threshold at Baseline is Useful for Establishing the Starting Dose in Peanut Oral Immunotherapy (OIT) J. A. Bird1, A. Clark2, M. G. Crain2, A. Arneson2; 1UT Southwestern Medical Center, Dallas, TX, 2Children’s Medical Center, Dallas, TX. RATIONALE: The majority of peanut OIT trials to date have initiated therapy with a standard dose of peanut flour. We hypothesized that by initiating therapy at a dose proportional to the eliciting threshold dose measured at entry challenge, subjects would be able to safely start at an accelerated dose. _ 7 kU/L METHODS: Subjects with ImmunoCAP peanut-specific IgE > _ 3mm underwent a and peanut skin prick test (SPT) wheal diameter > double-blind placebo-controlled food challenge (DBPCFC) to peanut. Those who reacted during the DBPCFC returned to receive peanut OIT with lightly roasted peanut flour. For subjects tolerating a cumulative dose of > 75mg of protein, the starting dose of therapy was initiated at 2 dosing increments below the highest single tolerated dose based on the build-up protocol. Subjects returned for dose escalation bi-weekly. RESULTS: Eleven of twelve subjects (ages 5 - 16 years) reacted to peanut during the DBPCFC, and 9/12 subjects tolerated > 75mg of protein. For the remaining 8 subjects, reaction-eliciting doses ranged from 75 to 250mg (median 112.5mg) of protein. Therapy was initiated between 12.5 and 150mg of protein (median 37.5mg). During dose escalation, 1 subject had 2 severe reactions precipitated by: (1.) taking a hot shower within 2 hours of the dose, and (2.) taking dose on an empty stomach. All other subjects complained of only mild symptoms, similar to reports from previous trials. CONCLUSION: Consideration for an individualized starting dose based on the eliciting dose threshold appears to safely accelerate the dosing schedule for subjects receiving peanut OIT.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
107
A Prospective, Randomized, Case Controlled Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated with Peanut Desensitization in Children with Peanut Allergies N. Berlin1, S. Maclachlan1, N. Leader1, D. Penn2, G. Sussman1,3; 1 Gordon Sussman Clinical Research Inc., Toronto, ON, CANADA, 2 Mast Cell Pharmaceuticals Inc., Raleigh, NC, 3University of Toronto, Toronto, ON, CANADA. RATIONALE: To decrease allergic reactions during oral peanut desensitization we studied the effect of premedication with ketotifen, an anti allergenic used to treat ocular allergy and allergic asthma. METHODS: 6 Patients (4M:2F) with prior histories of peanut anaphylaxis (grade 2 and specific IgE > 100) were enrolled in a single blind placebo controlled study, with escalating doses of ketotifen pretreatment of up to 4mg. A rush oral peanut desensitization protocol was used according to previous published studies, up to 50mg peanut flour (z25mg protein) on day-1, followed by a biweekly schedule of escalating doses. Ketotifen continued after day-1. RESULTS: All moderate to severe reactions (10) occurred in placebo patients and were gastrointestinal (abdominal cramps, nausea, vomiting, diarrhea). The overall day-1 reaction rate was 18.5% and all reactions occurred between the 3mg and 50mg doses. The overall reaction rate for the following 2 weeks was 38% (26% in treatment and 72% in placebo). 3 anaphylactic reactions occurred: day-1 placebo patient at 50mg dose (gastrointestinal, cutaneous); day-5 treatment patient at 50mg dose, occurred post exercise, (gastrointestinal, cutaneous, respiratory); day-6 placebo patient at 12mg dose, associated with fever, (gastrointestinal, cutaneous, respiratory), epinephrine was given and patient withdrew from study. Eosinophil counts were elevated for all patients upon 2nd visit, and decreased over time. CONCLUSIONS: Pretreatment with ketotifen 4mg greatly decreases side effects associated with the desensitization procedure, most of which were gastrointestinal. Eosinophilia was observed in all patients after day-1. We suspect that anti-inflammatory gastrointestinal cytoprotection may be the mechanism of action of ketotifen.
108
Oral Food Immunotherapy: Protective Doses Reached Within Two Months M. B. Levy, M. R. Goldberg, M. L. Stein, A. Elizur, L. Nachshon, Y. Katz; Assaf Harofe Medical Center, Tzrifin, ISRAEL. RATIONALE: Oral food immunotherapy (OFI) has been shown to be efficacious. Protocols vary as to the amount of time needed to reach doses that may be protective of an accidental product ingestion. METHODS: The clinical records of 252 patients enrolled in an active OFI program for milk, peanut and egg protein were reviewed. This individualized dose escalation protocol includes a 4 day induction-desensitization phase performed in a hospital based out-patient clinic where a maximal individualized tolerated dose (MITD) is determined. The MITD is consumed twice daily at home for 24 days and the cycle repeated. RESULTS: Patients ranged in age from 4-27 years (average 8.5 years). 152 (60%) were male. 125/252 (49.6%) had a history of asthma. Treatment groups included 235 milk, 12 peanut, and 5 egg patients. After completing at least three dose escalation sessions over two months, 178/208 (85%) of milk allergy patients were able to consume 180 mg or more, an amount considered to be protective for an accidental dairy contaminated product ingestion. After three sessions 6/8 (75%) of peanut patients were able to consume 300 mg or more, the protein equivalent of one peanut, and 2/4 (50%) of egg patients were able to consume 1500 mg or more, the protein equivalent of 1/4 of an egg. Treatment failures totaled 24/235 (9.5%). CONCLUSIONS: Using the current oral food immunotherapy protocol, the majority of milk, peanut and egg allergic patients are able to achieve a protective dose of allergenic protein within two months of treatment.