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Efficacy Of Omalizumab In Reducing Food Allergy
Abstracts AB135
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2
Six month course of peanut OIT leads to suppression of basophil activation which begins to wane within four weeks after OIT is stopped
Michael D. Kulis, PhD1, Caitlin M. Burk1, Xiaohong Yue, MS1, Huamei Zhang2, Rishu Guo, PhD1, Kelly Orgel1, Ping Ye, PhD1, Brian P. Vickery, MD, FAAAAI1,3, Edwin Kim, MD1, and A. Wesley Burks, MD1; 1University of North Carolina at Chapel Hill, Chapel Hill, NC, 2 Univerisity of North Carolina at Chapel Hill, Chapel Hill, NC, 3Aimmune Therapeutics, Brisbane, CA. RATIONALE: Peanut OIT can induce desensitization and is associated with suppression of effector cells. We aimed to investigate basophil activation as a marker of desensitization and sustained unresponsiveness after stopping therapy. METHODS: Peanut allergic subjects underwent entry challenges (OFC1) then 6 months of OIT and were assessed for desensitization (OFC2) and sustained unresponsiveness after OIT was stopped for 1-2 (OFC3) and 3-4 weeks (OFC4). Whole-blood basophil activation assays were performed at entry, during OIT, and OFC2-4. Basophils were assessed for CD63 after 30 minutes of ex vivo stimulation. RESULTS: Twenty subjects were enrolled and 16 completed the protocol. Clinical outcomes demonstrated desensitization with highest cumulative dose (HCD) tolerated increasing from a median of 21mg at OFC1 (range: 1–496mg) to 5000mg at OFC2 (range: 750–5000mg). The median HCD was 5000mg (range: 250mg–5000mg) at OFC3 but decreased to 3750mg (range: 750mg–5000mg) at OFC4. 3/16 (18.8%) demonstrated sustained unresponsiveness with 5000mg HCD at OFC4. During OIT, there was a decrease in %CD63+ basophils stimulated with peanut or anti-IgE (p<0.01). There was a significant increase in %CD63+ basophils from OFC2 to OFC4 (p<0.05), but not from OFC2 to OFC3, at all four doses of peanut used in the assay. An inverse correlation was found between % CD63+ basophils stimulated with 10ng/mL peanut and OFC2 outcomes (p<0.001), however, this was the only correlation detected. CONCLUSIONS: Six months of OIT leads to suppression of basophil activation and clinical desensitization, but the clinical effect, as well as basophil suppression, begins to wane when off OIT for 4 weeks.
431
Peanut Oral Immunotherapy (POIT) Dose Variations Do Not Result in Loss of Tolerance
Sara Anvari, MD, MS1, Daisy Tran, RN2, Avina H. Nguyen, CHES2, Sridevi Devaraj, PhD, DABCC, FACB3, and Carla M. Davis, MD, FAAAAI4; 1Baylor College of Medicine, Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX, 2Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX, 3 Baylor College of Medicine, Texas Children’s Hospital, Department of Pathology and Immunology, Houston, TX, 4Baylor College of Medicine and Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX. RATIONALE: The risk of allergic reactions during dose variation in POIT is considered high and lot variation in peanut flour potency could result in allergic responses in POIT patients. We hypothesized POIT subjects may tolerate variations in POIT dosing. METHODS: A prospective study of a 50% decrease in daily peanut protein dose for 2 weeks in POIT patients followed by an increase to prechange levels was performed. The following factors were assessed: gender; starting age of POIT; duration on POIT prior to dose change; peanut and Ara h 2specific IgE prior to POIT; threshold symptom eliciting dose with entry food challenge; and number of allergic reactions associated with increased peanut protein dose. Spearman’s rank correlation coefficient (r) was used to measure the correlation of the dose variation amount to the above factors. RESULTS: Eleven POIT patients [male:55%; median age 8(5-12) years; median POIT duration 3(2-7.5) months] with median peanut specific IgE 119(20.4-707) kU/L, tolerated increased peanut protein doses without allergic reactions [median dose increase: 40(14.4-450)mg]. The median
Ara h 2specific IgE was 165.5(11.9-504) kU/L in 8/11 patients. The amount of tolerated dose variations correlated with the duration on POIT prior to dose change (Spearman r50.72;95% CI 0.184-0.923;p50.013). CONCLUSIONS: No symptoms were observed in this POIT cohort given a 50% POIT dose variation. The risk of allergic reactions with variations in daily peanut protein dose in POIT patients may not be as high as previously considered. This conclusion, however, will require further direct testing on a larger population with variable dose changes.
432
Efficacy Of Omalizumab In Reducing Food Allergy
Varaz Bozoghlanian, MD, Saraleen Benouni, MD, Lananh T. Do, MD FAAAAI, Lee E. Sheinkopf, MD, and Roger M. Katz, MD, FAAAAI; Allergy Asthma Care Center, Inc., Los Angeles, CA. RATIONALE: Several studies have reported therapeutic benefit of omalizumab in reducing severity of symptoms in food allergy. We sought to determine if these findings are applicable to patients in our own clinic. METHODS: A retrospective chart review was performed on adult and pediatric patients receiving omalizumb for moderate to severe persistent asthma. Analysis was performed on patients with concomitant food allergy as determined by positive skin prick testing combined with clinical history of IgE-mediated reactions to those foods. Symptoms prior to starting omalizumab were compared to symptoms that occurred after accidental ingestion while receiving omalizumab. RESULTS: Over a four-year period, 169 patients were identified who received omalizumab for asthma. From this group, 17 patients had food allergy identified as above. Male to female ratio was 5:12, ages 13-66 (mean 44), with total IgE 53-4237 kU/L (mean 854). Omalizumab dosing ranged from 150mg every 2 weeks to 300mg every 4 weeks. The most common food allergens were peanuts (5 patients), soy (4), tree nuts (3), vertebrate fish (3), wheat (2), shellfish (2), and corn (2). Over the study period, 13 out of 17 patients reported accidental ingestion at least once. None of the exposures caused serious reactions, and none required epinephrine. Ten out of 13 patients reported that prior to omalizumab, ingestion of similar quantities of their allergenic foods had caused systemic reactions. CONCLUSIONS: Omalizumab appears to reduce the severity of adverse reactions in patients with IgE-mediated food hypersensitivity. Oral food challenges are needed to confirm these results.
SUNDAY
430
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2
Six month course of peanut OIT leads to suppression of basophil activation which begins to wane within four weeks after OIT is stopped
Michael D. Kulis, PhD1, Caitlin M. Burk1, Xiaohong Yue, MS1, Huamei Zhang2, Rishu Guo, PhD1, Kelly Orgel1, Ping Ye, PhD1, Brian P. Vickery, MD, FAAAAI1,3, Edwin Kim, MD1, and A. Wesley Burks, MD1; 1University of North Carolina at Chapel Hill, Chapel Hill, NC, 2 Univerisity of North Carolina at Chapel Hill, Chapel Hill, NC, 3Aimmune Therapeutics, Brisbane, CA. RATIONALE: Peanut OIT can induce desensitization and is associated with suppression of effector cells. We aimed to investigate basophil activation as a marker of desensitization and sustained unresponsiveness after stopping therapy. METHODS: Peanut allergic subjects underwent entry challenges (OFC1) then 6 months of OIT and were assessed for desensitization (OFC2) and sustained unresponsiveness after OIT was stopped for 1-2 (OFC3) and 3-4 weeks (OFC4). Whole-blood basophil activation assays were performed at entry, during OIT, and OFC2-4. Basophils were assessed for CD63 after 30 minutes of ex vivo stimulation. RESULTS: Twenty subjects were enrolled and 16 completed the protocol. Clinical outcomes demonstrated desensitization with highest cumulative dose (HCD) tolerated increasing from a median of 21mg at OFC1 (range: 1–496mg) to 5000mg at OFC2 (range: 750–5000mg). The median HCD was 5000mg (range: 250mg–5000mg) at OFC3 but decreased to 3750mg (range: 750mg–5000mg) at OFC4. 3/16 (18.8%) demonstrated sustained unresponsiveness with 5000mg HCD at OFC4. During OIT, there was a decrease in %CD63+ basophils stimulated with peanut or anti-IgE (p<0.01). There was a significant increase in %CD63+ basophils from OFC2 to OFC4 (p<0.05), but not from OFC2 to OFC3, at all four doses of peanut used in the assay. An inverse correlation was found between % CD63+ basophils stimulated with 10ng/mL peanut and OFC2 outcomes (p<0.001), however, this was the only correlation detected. CONCLUSIONS: Six months of OIT leads to suppression of basophil activation and clinical desensitization, but the clinical effect, as well as basophil suppression, begins to wane when off OIT for 4 weeks.
431
Peanut Oral Immunotherapy (POIT) Dose Variations Do Not Result in Loss of Tolerance
Sara Anvari, MD, MS1, Daisy Tran, RN2, Avina H. Nguyen, CHES2, Sridevi Devaraj, PhD, DABCC, FACB3, and Carla M. Davis, MD, FAAAAI4; 1Baylor College of Medicine, Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX, 2Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX, 3 Baylor College of Medicine, Texas Children’s Hospital, Department of Pathology and Immunology, Houston, TX, 4Baylor College of Medicine and Texas Children’s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Houston, TX. RATIONALE: The risk of allergic reactions during dose variation in POIT is considered high and lot variation in peanut flour potency could result in allergic responses in POIT patients. We hypothesized POIT subjects may tolerate variations in POIT dosing. METHODS: A prospective study of a 50% decrease in daily peanut protein dose for 2 weeks in POIT patients followed by an increase to prechange levels was performed. The following factors were assessed: gender; starting age of POIT; duration on POIT prior to dose change; peanut and Ara h 2specific IgE prior to POIT; threshold symptom eliciting dose with entry food challenge; and number of allergic reactions associated with increased peanut protein dose. Spearman’s rank correlation coefficient (r) was used to measure the correlation of the dose variation amount to the above factors. RESULTS: Eleven POIT patients [male:55%; median age 8(5-12) years; median POIT duration 3(2-7.5) months] with median peanut specific IgE 119(20.4-707) kU/L, tolerated increased peanut protein doses without allergic reactions [median dose increase: 40(14.4-450)mg]. The median
Ara h 2specific IgE was 165.5(11.9-504) kU/L in 8/11 patients. The amount of tolerated dose variations correlated with the duration on POIT prior to dose change (Spearman r50.72;95% CI 0.184-0.923;p50.013). CONCLUSIONS: No symptoms were observed in this POIT cohort given a 50% POIT dose variation. The risk of allergic reactions with variations in daily peanut protein dose in POIT patients may not be as high as previously considered. This conclusion, however, will require further direct testing on a larger population with variable dose changes.
432
Efficacy Of Omalizumab In Reducing Food Allergy
Varaz Bozoghlanian, MD, Saraleen Benouni, MD, Lananh T. Do, MD FAAAAI, Lee E. Sheinkopf, MD, and Roger M. Katz, MD, FAAAAI; Allergy Asthma Care Center, Inc., Los Angeles, CA. RATIONALE: Several studies have reported therapeutic benefit of omalizumab in reducing severity of symptoms in food allergy. We sought to determine if these findings are applicable to patients in our own clinic. METHODS: A retrospective chart review was performed on adult and pediatric patients receiving omalizumb for moderate to severe persistent asthma. Analysis was performed on patients with concomitant food allergy as determined by positive skin prick testing combined with clinical history of IgE-mediated reactions to those foods. Symptoms prior to starting omalizumab were compared to symptoms that occurred after accidental ingestion while receiving omalizumab. RESULTS: Over a four-year period, 169 patients were identified who received omalizumab for asthma. From this group, 17 patients had food allergy identified as above. Male to female ratio was 5:12, ages 13-66 (mean 44), with total IgE 53-4237 kU/L (mean 854). Omalizumab dosing ranged from 150mg every 2 weeks to 300mg every 4 weeks. The most common food allergens were peanuts (5 patients), soy (4), tree nuts (3), vertebrate fish (3), wheat (2), shellfish (2), and corn (2). Over the study period, 13 out of 17 patients reported accidental ingestion at least once. None of the exposures caused serious reactions, and none required epinephrine. Ten out of 13 patients reported that prior to omalizumab, ingestion of similar quantities of their allergenic foods had caused systemic reactions. CONCLUSIONS: Omalizumab appears to reduce the severity of adverse reactions in patients with IgE-mediated food hypersensitivity. Oral food challenges are needed to confirm these results.
SUNDAY
430