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Safety of a Short Ragweed Allergy Immunotherapy Tablet in Adults With Ragweed-Induced Allergic Rhinoconjunctivitis and Asthma
AB48 Abstracts
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Efficacy of Timothy Grass Allergy Immunotherapy Tablet During Peak Grass Pollen Season in North American Children and Adolescents J. Maloney1, D. Skoner2, H. Nolte1, S. Gawchik3, M. Blaiss4; 1Merck Research Laboratories, Kenilworth, NJ, 2Drexel University College of Medicine, Philadelphia, PA, 3Asthma and Allergy Associates, Upland, PA, 4 University of Tennessee Health Science Center, Memphis, TN. RATIONALE: Children with allergic rhinoconjunctivitis (ARC) may experience discomfort and activity limitations, especially during peak grass pollen season (pGPS) when symptoms are the most severe. Efficacy of Timothy grass allergy immunotherapy tablets (grass AIT) during pGPS was evaluated in a randomized, double-blind efficacy/safety trial in North American children/adolescents. METHODS: 344 subjects (5-17y) with grass pollen-induced ARC with/ without asthma received once-daily 2800 BAU-standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, ;15mg Phl p 5) or placebo a median of 16 weeks before and during GPS 2009. pGPS was defined as the 15-consecutive-day period with the highest moving average pollen count. The daily symptom score (DSS), daily medication score (DMS), total combined score (TCS5sum of DSS and DMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores (pediatric and adolescent) were assessed. Safety was monitored through adverse event (AE) reporting. RESULTS: 89% of subjects were multisensitized. Mean pollen counts (grains/m3/d) were: GPS528, pGPS548. Relative to placebo, improvements in TCS, DSS, DMS, and RQLQ with grass AIT were numerically greater during pGPS (31%, P<0.001; 28%, P<0.001; 100%, P50.001; and 38%, P50.005, respectively) than the entire GPS (26%, P<0.001; 25%, P50.005; 81%, P50.006; and 18%, P50.04, respectively). No grass AIT-related serious AEs or systemic allergic reactions were reported. CONCLUSIONS: Grass AIT treatment yielded significant improvements during pGPS (when pollen counts are highest and symptoms may be most severe) that were greater than during the entire GPS. Grass AIT provided chil_5 years with Timothy (and other cross-reactive Festucoideae) dren aged > grass pollen-induced ARC with safe, effective symptom relief.
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Lower Respiratory-Related Events in Adults and Children With Allergic Rhinoconjunctivitis Receiving Timothy Grass Allergy Immunotherapy Tablet H. Nolte1, H. S. Nelson2, M. Blaiss3, A. Bufe4, R. Dahl5, S. R. Durham6; 1 Merck Research Laboratories, Kenilworth, NJ, 2National Jewish Health, Denver, CO, 3University of Tennessee Health Science Center, Memphis, TN, 4Ruhr University, Bochum, GERMANY, 5Aarhus University Hospital, Aarhus, DENMARK, 6Royal Brompton and Harefield Hospitals National Health Service Trust and Imperial College, London, UNITED KINGDOM. RATIONALE: Asthma may be a risk factor for adverse events when treating patients with immunotherapy. The purported advantage of sublingual immunotherapy is improved safety. The safety of Timothy grass allergy immunotherapy tablets (grass AIT) in asthma patients was further characterized by assessing lower respiratory-related events in subjects with grass pollen-induced allergic rhinoconjunctivitis (ARC) with/without asthma. METHODS: Safety data pooled from 7 randomized, placebo-controlled trials of 2800 BAU-standardized once-daily grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, ;15mg Phl p 5) in 2096 adults (5 phase II/III trials) and 598 children (5-17y; 2 phase III trials) were assessed using subject-recorded lower respiratory-related events (asthma, dyspnea, wheezing, cough, chest tightness/discomfort, exercise-induced symptoms). Of asthmatic subjects, only those with well-controlled intermit_70% tent-to-moderate asthma and forced expiratory volume in 1 second > predicted, were included in the studies. RESULTS: For asthmatic adults (n5516), the mean incidence of lower respiratory-related events was 59.6% in grass AIT subjects and 66.8% in placebo subjects; for non-asthmatic adults (n51580), the incidence was 48.9% in grass AIT subjects and 46.9% in placebo subjects. In asthmatic children (n5190), the incidence of lower respiratory-related events was 86.7% in grass AIT subjects and 94.6% in placebo subjects; for non-asthmatic children (n5408) the incidence was 74.0% in grass AIT
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
subjects and 80.4% in placebo subjects. No apparent differences in severity distribution for these events were observed. CONCLUSION: Pooled safety results from adult and pediatric trials involving >2500 subjects did not indicate an adverse safety signal for grass AIT in subjects with ARC and stable, well-controlled intermittent-to-moderate asthma.
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Safety of a Short Ragweed Allergy Immunotherapy Tablet in Adults With Ragweed-Induced Allergic Rhinoconjunctivitis and Asthma D. I. Bernstein1, G. J. Atiee2, J. Maloney3, H. Nolte3, A. S. Nayak4; 1University of Cincinnati College of Medicine, Cincinnati, OH, 2ICON Development Solutions, San Antonio, TX, 3Merck Research Laboratories, Kenilworth, NJ, 4Sneeze, Wheeze & Itch Associates, LLC, Normal, IL. RATIONALE: A short ragweed allergy immunotherapy tablet (ragweed AIT) may provide a safer alternative to subcutaneous immunotherapy. METHODS: The safety of Ambrosia artemisiifolia (Amb-a5common/ short ragweed) AIT in subjects with allergic rhinoconjunctivitis was assessed in two 28-day, randomized, double-blind trials. In RT-01 (aged 18-50y; phase I), ragweed AIT dosage groups of once-daily 3, 6, 12, 24 or 50 Amb-a 1-Units (total n540) or placebo (n513) were initiated in a staggered manner at 7-day intervals with no dose buildup. Enrollment in the 50 Amb-a 1-Unit arm was discontinued for safety reasons. In _50y; phase II), ragweed AIT doses of 6 (n569) or 12 P06081 (aged > (n567) Amb-a 1-Units or placebo (n567) were administered once-daily. Adverse events (AEs) were assessed in both trials. RESULTS: In RT-01, the most frequently reported treatment-related (TR) AEs reported across all doses were oral pruritus (25/40, 63%), ear pruritus (11/40, 28%), eye pruritus (8/40, 20%), nasal passage irritation (4/40, 10%), and skin pruritus (2/40, 5%) and discontinuations due to AEs were: ragweed AIT, n54/40; placebo, n50/13. No safety differences were observed between subjects with or without ragweed-induced asthma (ragweed AIT, n55; placebo, n52). In P06081, for both doses the most frequently reported TRAEs were oral pruritus (22/136 subjects,16%), throat irritation (16/136, 12%), and ear pruritus (13/136, 10%) and discontinuations due to AEs were: ragweed AIT, n58/136; placebo, n512/67. No asthma or dyspnea TRAEs, serious TRAEs, or systemic allergic reactions were reported in either trial. _24 Amb-a 1-Units CONCLUSIONS: Ragweed AIT once-daily at doses < in adults >18 years without dose buildup was well-tolerated.
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Systemic Reactions in a Sample of Multiallergen Cluster Schedule Immunotherapy Patients vs. Conventional Schedule Patients L. J. Stillman; Allergy & Asthma Center, Fort Lauderdale, FL. RATIONALE: Cluster schedule subcutaneous immunotherapy protocols aim at reaching the dose-maintenance period faster than the conventional method, making them more convenient for patients. We examined the number of systemic reactions in a sample of cluster schedule patients versus conventional schedule patients to determine if the safety profiles are similar. METHODS: This study was a controlled retrospective analysis of the number of systemic reactions in a sample of cluster schedule subcutaneous immunotherapy patients versus conventional schedule immunotherapy patients. Patients in the cluster group were selected based on a minimum of a 5mm wheal on percutaneous skin testing to dust mites, cat, dog, or ragweed, plus at least one additional inhalant allergen. The control group consisted of patients currently receiving conventional schedule immunotherapy, who met the same skin test reactivity criteria. The cluster schedule used in the study was based on the Allergen Immunotherapy Practice Parameter Second Update, consisting of 8 visits and 18 steps. RESULTS: No statistically significant diffierence in the proportion of systemic reactions between the cluster group as compared to the conventional (N541; p5.414). CONCLUSIONS: The safety of cluster schedule immunotherapy is similar to that of the conventional schedule, making it a desirable alternative for many patients, as it saves time, improves patient compliance, and is more convenient.
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Efficacy of Timothy Grass Allergy Immunotherapy Tablet During Peak Grass Pollen Season in North American Children and Adolescents J. Maloney1, D. Skoner2, H. Nolte1, S. Gawchik3, M. Blaiss4; 1Merck Research Laboratories, Kenilworth, NJ, 2Drexel University College of Medicine, Philadelphia, PA, 3Asthma and Allergy Associates, Upland, PA, 4 University of Tennessee Health Science Center, Memphis, TN. RATIONALE: Children with allergic rhinoconjunctivitis (ARC) may experience discomfort and activity limitations, especially during peak grass pollen season (pGPS) when symptoms are the most severe. Efficacy of Timothy grass allergy immunotherapy tablets (grass AIT) during pGPS was evaluated in a randomized, double-blind efficacy/safety trial in North American children/adolescents. METHODS: 344 subjects (5-17y) with grass pollen-induced ARC with/ without asthma received once-daily 2800 BAU-standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, ;15mg Phl p 5) or placebo a median of 16 weeks before and during GPS 2009. pGPS was defined as the 15-consecutive-day period with the highest moving average pollen count. The daily symptom score (DSS), daily medication score (DMS), total combined score (TCS5sum of DSS and DMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores (pediatric and adolescent) were assessed. Safety was monitored through adverse event (AE) reporting. RESULTS: 89% of subjects were multisensitized. Mean pollen counts (grains/m3/d) were: GPS528, pGPS548. Relative to placebo, improvements in TCS, DSS, DMS, and RQLQ with grass AIT were numerically greater during pGPS (31%, P<0.001; 28%, P<0.001; 100%, P50.001; and 38%, P50.005, respectively) than the entire GPS (26%, P<0.001; 25%, P50.005; 81%, P50.006; and 18%, P50.04, respectively). No grass AIT-related serious AEs or systemic allergic reactions were reported. CONCLUSIONS: Grass AIT treatment yielded significant improvements during pGPS (when pollen counts are highest and symptoms may be most severe) that were greater than during the entire GPS. Grass AIT provided chil_5 years with Timothy (and other cross-reactive Festucoideae) dren aged > grass pollen-induced ARC with safe, effective symptom relief.
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Lower Respiratory-Related Events in Adults and Children With Allergic Rhinoconjunctivitis Receiving Timothy Grass Allergy Immunotherapy Tablet H. Nolte1, H. S. Nelson2, M. Blaiss3, A. Bufe4, R. Dahl5, S. R. Durham6; 1 Merck Research Laboratories, Kenilworth, NJ, 2National Jewish Health, Denver, CO, 3University of Tennessee Health Science Center, Memphis, TN, 4Ruhr University, Bochum, GERMANY, 5Aarhus University Hospital, Aarhus, DENMARK, 6Royal Brompton and Harefield Hospitals National Health Service Trust and Imperial College, London, UNITED KINGDOM. RATIONALE: Asthma may be a risk factor for adverse events when treating patients with immunotherapy. The purported advantage of sublingual immunotherapy is improved safety. The safety of Timothy grass allergy immunotherapy tablets (grass AIT) in asthma patients was further characterized by assessing lower respiratory-related events in subjects with grass pollen-induced allergic rhinoconjunctivitis (ARC) with/without asthma. METHODS: Safety data pooled from 7 randomized, placebo-controlled trials of 2800 BAU-standardized once-daily grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, ;15mg Phl p 5) in 2096 adults (5 phase II/III trials) and 598 children (5-17y; 2 phase III trials) were assessed using subject-recorded lower respiratory-related events (asthma, dyspnea, wheezing, cough, chest tightness/discomfort, exercise-induced symptoms). Of asthmatic subjects, only those with well-controlled intermit_70% tent-to-moderate asthma and forced expiratory volume in 1 second > predicted, were included in the studies. RESULTS: For asthmatic adults (n5516), the mean incidence of lower respiratory-related events was 59.6% in grass AIT subjects and 66.8% in placebo subjects; for non-asthmatic adults (n51580), the incidence was 48.9% in grass AIT subjects and 46.9% in placebo subjects. In asthmatic children (n5190), the incidence of lower respiratory-related events was 86.7% in grass AIT subjects and 94.6% in placebo subjects; for non-asthmatic children (n5408) the incidence was 74.0% in grass AIT
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
subjects and 80.4% in placebo subjects. No apparent differences in severity distribution for these events were observed. CONCLUSION: Pooled safety results from adult and pediatric trials involving >2500 subjects did not indicate an adverse safety signal for grass AIT in subjects with ARC and stable, well-controlled intermittent-to-moderate asthma.
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Safety of a Short Ragweed Allergy Immunotherapy Tablet in Adults With Ragweed-Induced Allergic Rhinoconjunctivitis and Asthma D. I. Bernstein1, G. J. Atiee2, J. Maloney3, H. Nolte3, A. S. Nayak4; 1University of Cincinnati College of Medicine, Cincinnati, OH, 2ICON Development Solutions, San Antonio, TX, 3Merck Research Laboratories, Kenilworth, NJ, 4Sneeze, Wheeze & Itch Associates, LLC, Normal, IL. RATIONALE: A short ragweed allergy immunotherapy tablet (ragweed AIT) may provide a safer alternative to subcutaneous immunotherapy. METHODS: The safety of Ambrosia artemisiifolia (Amb-a5common/ short ragweed) AIT in subjects with allergic rhinoconjunctivitis was assessed in two 28-day, randomized, double-blind trials. In RT-01 (aged 18-50y; phase I), ragweed AIT dosage groups of once-daily 3, 6, 12, 24 or 50 Amb-a 1-Units (total n540) or placebo (n513) were initiated in a staggered manner at 7-day intervals with no dose buildup. Enrollment in the 50 Amb-a 1-Unit arm was discontinued for safety reasons. In _50y; phase II), ragweed AIT doses of 6 (n569) or 12 P06081 (aged > (n567) Amb-a 1-Units or placebo (n567) were administered once-daily. Adverse events (AEs) were assessed in both trials. RESULTS: In RT-01, the most frequently reported treatment-related (TR) AEs reported across all doses were oral pruritus (25/40, 63%), ear pruritus (11/40, 28%), eye pruritus (8/40, 20%), nasal passage irritation (4/40, 10%), and skin pruritus (2/40, 5%) and discontinuations due to AEs were: ragweed AIT, n54/40; placebo, n50/13. No safety differences were observed between subjects with or without ragweed-induced asthma (ragweed AIT, n55; placebo, n52). In P06081, for both doses the most frequently reported TRAEs were oral pruritus (22/136 subjects,16%), throat irritation (16/136, 12%), and ear pruritus (13/136, 10%) and discontinuations due to AEs were: ragweed AIT, n58/136; placebo, n512/67. No asthma or dyspnea TRAEs, serious TRAEs, or systemic allergic reactions were reported in either trial. _24 Amb-a 1-Units CONCLUSIONS: Ragweed AIT once-daily at doses < in adults >18 years without dose buildup was well-tolerated.
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Systemic Reactions in a Sample of Multiallergen Cluster Schedule Immunotherapy Patients vs. Conventional Schedule Patients L. J. Stillman; Allergy & Asthma Center, Fort Lauderdale, FL. RATIONALE: Cluster schedule subcutaneous immunotherapy protocols aim at reaching the dose-maintenance period faster than the conventional method, making them more convenient for patients. We examined the number of systemic reactions in a sample of cluster schedule patients versus conventional schedule patients to determine if the safety profiles are similar. METHODS: This study was a controlled retrospective analysis of the number of systemic reactions in a sample of cluster schedule subcutaneous immunotherapy patients versus conventional schedule immunotherapy patients. Patients in the cluster group were selected based on a minimum of a 5mm wheal on percutaneous skin testing to dust mites, cat, dog, or ragweed, plus at least one additional inhalant allergen. The control group consisted of patients currently receiving conventional schedule immunotherapy, who met the same skin test reactivity criteria. The cluster schedule used in the study was based on the Allergen Immunotherapy Practice Parameter Second Update, consisting of 8 visits and 18 steps. RESULTS: No statistically significant diffierence in the proportion of systemic reactions between the cluster group as compared to the conventional (N541; p5.414). CONCLUSIONS: The safety of cluster schedule immunotherapy is similar to that of the conventional schedule, making it a desirable alternative for many patients, as it saves time, improves patient compliance, and is more convenient.