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Evaluation Of Acoustic Rhinometry In Histamine Nasal Provocation Test In Children and Adolescents
AB222 Abstracts
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Magnitude Of Changes In Patient Symptom and Medication Scores In Grass Allergy Immunotherapy Trials: Dependency On Levels Of Pollen Exposure Dr. Hendrik Nolte, MD, PhD1, Prof. Stephen R. Durham, MA, MD, FRCP2, Dr. Harold S. Nelson, MD, FAAAAI3, Dr. David I. Bernstein, MD, FAAAAI4, Dr. Peter S. Creticos, MD, FAAAAI5, Dr. Ziliang Li, PhD1, Dr. Jens Andersen, PhD6; 1Merck, Whitehouse Station, NJ, 2Imperial College London, London, United Kingdom, 3National Jewish Health, Denver, CO, 4Bernstein Allergy Group, Cincinnati, OH, 5 Johns Hopkins Division of Allergy & Clinical Immunology, 6ALKAbell o, Hørsholm, Denmark. RATIONALE: While symptomatic therapy trials for seasonal allergic rhinitis with or without conjunctivitis (AR/C) begin while subjects have symptoms, pollen immunotherapy trials generally begin treatment preseasonally and assess efficacy during seasonal exposure. We investigated the impact of pollen exposure variability on magnitude of recorded immunotherapy treatment effect. METHODS: Data from 7 North American and European randomized placebo-controlled trials of standardized Timothy grass sublingual immunotherapy tablet (SLIT-T), MK-7243 (Merck/ALK; 2800 BAU of Phleum pratense) were included (omitting 1 trial, as lack of pollencount/symptom relationship suggested etiology other than grass pollen exposure). Predefined preseasonal treatment ranged from 8-16 weeks. _10 grains/m3 Boundaries of 3 consecutive days with pollen count > defined grass pollen season (GPS). We assessed correlation of between-treatment difference in total combined score (TCS; combined symptom/medication scores) per trial or trial year to first-20-days-ofGPS cumulative grass pollen count and entire-GPS average pollen count. RESULTS: Data included 1798/1765 MK-7243/placebo subjects. TCS for both groups increased with grass pollen counts. Treatment effect in TCS in each trial (or trial year) was correlated to cumulative grass pollen count during first 20 days of GPS (R250.803). Correlation was also seen between TCS and average pollen count over entire GPS (R250.464). CONCLUSIONS: Post hoc analysis of 7 MK-7243 trials demonstrates that treatment effect magnitude was highly correlated to pollen exposure. Difference in pollen-exposure levels should be considered when comparing results among pollen immunotherapy trials and should also be considered with other methodological differences when comparing to symptomatic medication trials. The early-season– exposure/efficacy correlation does not confirm prevailing theories regarding priming.
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Evaluation Of Acoustic Rhinometry In Histamine Nasal Provocation Test In Children and Adolescents Dr. Fausto Y. Matsumoto1, Dr. Gustavo Wandalsen, MD2, Dr. Aline Mendes3, Prof. Dirceu Sole, MD, PhD4; 1Federal University of S~ao Paulo, S~ao Paulo, Brazil, 2UNIFESP, Sao Paulo, Brazil, 3Federal University of S~ao Paulo, Brazil, 4Federal University of Sao Paulo, Sao Paulo, Brazil. RATIONALE: although acoustic rhinometry (AR) is considered a well established technique to evaluate nasal patency its role in nasal provocation tests is still to be defined, especially in children and adolescents. METHODS: Twenty patients with allergic rhinitis and 18 controls were submitted to histamine nasal provocation tests. AR and anterior active rhinomanometry were performed after bilateral instillation of 0.14ml of nasal saline and histamine (0.12, 0.25, 0.5, 1, 2, 4 and 8mg/ml) until 100% increase in total nasal airflow resistance (NAR). Different AR parameters were recorded (nasal volume in first 5cm [V5] and 4cm, minimal cross
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
sectional area between 0 and 2.2cm [MC1] and between 2.2 and 5.4cm [MC2]). RESULTS: Among all analyzed parameters, V5 showed to have the best inverse correlation with NAR both in the rhinitis and in the total group (r5 -0.62, p50.004 and r5 -0.56, p50.001, respectively). At the end of the provocation test a mean increase of 127% (CI95%: 113% to 141%) in NAR was observed in the rhinitis group that corresponded to a mean decrease of 24.5% (CI95%: 22.5% to 26.5%) in V5. Twenty percent fall in V5 showed to have the best balance between sensitivity (88.2%) and specificity (97.1%) among all analyzed endpoints (14% to 34% fall in V5). CONCLUSIONS: AR is able to discriminate children and adolescents with allergic rhinitis from controls when submitted to histamine nasal provocation test. V5 showed the highest correlation with NAR among all studied AR parameters and 20% fall in V5 was identified as the best endpoint in such challenges.
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EQ-5D Health Utility Values In The Treatment Of Seasonal Grass Pollen Induced Rhinoconjunctivitis Mr. Jakob N. Andreasen1, Dr. Chris Poole2, Dr. Christian Bannister3, Dr. Jens Andersen, PhD4, Mr. Niels Serup-Hansen1; 1ALK, Denmark, 2 Cardiff University, Cardiff, Wales, 3Cardiff University, 4ALK-Abello, Hørsholm, Denmark. RATIONALE: Standard clinical efficacy endpoints in allergen immunotherapy trials include the daily Rhinoconjunctivitis Symptom Score (RSS) and daily Rhinoconjunctivitis Medication Score (RMS). However, measurement of subjects’ QoL in terms of health utility is also necessary to characterise changes in health status. In this study, we aimed to determine a relationship between standard efficacy endpoints and the health utility. METHODS: Data from a 5-year DBPC phase III trial (GT-08, ALK, Denmark) in subjects with grass pollen induced rhinoconjunctivitis were analysed. During each pollen season, subjects recorded daily their RSS and RMS and weekly the EQ-5D index. A two-stage model was constructed: 1) binomial modelling of subjects with ‘‘perfect health’’ (EQ-5D utility51) and 2) Gaussian modelling of EQ-5D utilities< 1. The utility during each grass pollen season was calculated as area under the curve. RESULTS: A total of 16,690 weekly and 137,792 daily EQ-5D observations were recorded over the trial period. The binomial model showed the daily RSS and RMS to be the two most important predictors of ‘‘perfect health’’ (RSS: OR50.729; p< 0.001; RMS: OR50.841; p< 0.001). The Gaussian model of subjects with ‘‘imperfect health’’ confirmed this correlation. Based on relationship the average annual utility was estimated to 2.2 QALD. CONCLUSIONS: In a clinical trial including subjects with grass pollen induced rhinoconjunctivitis, the daily RSS and RMS were found to be suitable predictors of the EQ-5D health utility. The findings confirm the beneficial impact of the SQ-standardised Timothy grass allergy immunotherapy tablet (75,000 SQ-T/2,800 BAU, ALK) on health utilities with a clinical relevant QALY gain.
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Magnitude Of Changes In Patient Symptom and Medication Scores In Grass Allergy Immunotherapy Trials: Dependency On Levels Of Pollen Exposure Dr. Hendrik Nolte, MD, PhD1, Prof. Stephen R. Durham, MA, MD, FRCP2, Dr. Harold S. Nelson, MD, FAAAAI3, Dr. David I. Bernstein, MD, FAAAAI4, Dr. Peter S. Creticos, MD, FAAAAI5, Dr. Ziliang Li, PhD1, Dr. Jens Andersen, PhD6; 1Merck, Whitehouse Station, NJ, 2Imperial College London, London, United Kingdom, 3National Jewish Health, Denver, CO, 4Bernstein Allergy Group, Cincinnati, OH, 5 Johns Hopkins Division of Allergy & Clinical Immunology, 6ALKAbell o, Hørsholm, Denmark. RATIONALE: While symptomatic therapy trials for seasonal allergic rhinitis with or without conjunctivitis (AR/C) begin while subjects have symptoms, pollen immunotherapy trials generally begin treatment preseasonally and assess efficacy during seasonal exposure. We investigated the impact of pollen exposure variability on magnitude of recorded immunotherapy treatment effect. METHODS: Data from 7 North American and European randomized placebo-controlled trials of standardized Timothy grass sublingual immunotherapy tablet (SLIT-T), MK-7243 (Merck/ALK; 2800 BAU of Phleum pratense) were included (omitting 1 trial, as lack of pollencount/symptom relationship suggested etiology other than grass pollen exposure). Predefined preseasonal treatment ranged from 8-16 weeks. _10 grains/m3 Boundaries of 3 consecutive days with pollen count > defined grass pollen season (GPS). We assessed correlation of between-treatment difference in total combined score (TCS; combined symptom/medication scores) per trial or trial year to first-20-days-ofGPS cumulative grass pollen count and entire-GPS average pollen count. RESULTS: Data included 1798/1765 MK-7243/placebo subjects. TCS for both groups increased with grass pollen counts. Treatment effect in TCS in each trial (or trial year) was correlated to cumulative grass pollen count during first 20 days of GPS (R250.803). Correlation was also seen between TCS and average pollen count over entire GPS (R250.464). CONCLUSIONS: Post hoc analysis of 7 MK-7243 trials demonstrates that treatment effect magnitude was highly correlated to pollen exposure. Difference in pollen-exposure levels should be considered when comparing results among pollen immunotherapy trials and should also be considered with other methodological differences when comparing to symptomatic medication trials. The early-season– exposure/efficacy correlation does not confirm prevailing theories regarding priming.
768
Evaluation Of Acoustic Rhinometry In Histamine Nasal Provocation Test In Children and Adolescents Dr. Fausto Y. Matsumoto1, Dr. Gustavo Wandalsen, MD2, Dr. Aline Mendes3, Prof. Dirceu Sole, MD, PhD4; 1Federal University of S~ao Paulo, S~ao Paulo, Brazil, 2UNIFESP, Sao Paulo, Brazil, 3Federal University of S~ao Paulo, Brazil, 4Federal University of Sao Paulo, Sao Paulo, Brazil. RATIONALE: although acoustic rhinometry (AR) is considered a well established technique to evaluate nasal patency its role in nasal provocation tests is still to be defined, especially in children and adolescents. METHODS: Twenty patients with allergic rhinitis and 18 controls were submitted to histamine nasal provocation tests. AR and anterior active rhinomanometry were performed after bilateral instillation of 0.14ml of nasal saline and histamine (0.12, 0.25, 0.5, 1, 2, 4 and 8mg/ml) until 100% increase in total nasal airflow resistance (NAR). Different AR parameters were recorded (nasal volume in first 5cm [V5] and 4cm, minimal cross
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
sectional area between 0 and 2.2cm [MC1] and between 2.2 and 5.4cm [MC2]). RESULTS: Among all analyzed parameters, V5 showed to have the best inverse correlation with NAR both in the rhinitis and in the total group (r5 -0.62, p50.004 and r5 -0.56, p50.001, respectively). At the end of the provocation test a mean increase of 127% (CI95%: 113% to 141%) in NAR was observed in the rhinitis group that corresponded to a mean decrease of 24.5% (CI95%: 22.5% to 26.5%) in V5. Twenty percent fall in V5 showed to have the best balance between sensitivity (88.2%) and specificity (97.1%) among all analyzed endpoints (14% to 34% fall in V5). CONCLUSIONS: AR is able to discriminate children and adolescents with allergic rhinitis from controls when submitted to histamine nasal provocation test. V5 showed the highest correlation with NAR among all studied AR parameters and 20% fall in V5 was identified as the best endpoint in such challenges.
769
EQ-5D Health Utility Values In The Treatment Of Seasonal Grass Pollen Induced Rhinoconjunctivitis Mr. Jakob N. Andreasen1, Dr. Chris Poole2, Dr. Christian Bannister3, Dr. Jens Andersen, PhD4, Mr. Niels Serup-Hansen1; 1ALK, Denmark, 2 Cardiff University, Cardiff, Wales, 3Cardiff University, 4ALK-Abello, Hørsholm, Denmark. RATIONALE: Standard clinical efficacy endpoints in allergen immunotherapy trials include the daily Rhinoconjunctivitis Symptom Score (RSS) and daily Rhinoconjunctivitis Medication Score (RMS). However, measurement of subjects’ QoL in terms of health utility is also necessary to characterise changes in health status. In this study, we aimed to determine a relationship between standard efficacy endpoints and the health utility. METHODS: Data from a 5-year DBPC phase III trial (GT-08, ALK, Denmark) in subjects with grass pollen induced rhinoconjunctivitis were analysed. During each pollen season, subjects recorded daily their RSS and RMS and weekly the EQ-5D index. A two-stage model was constructed: 1) binomial modelling of subjects with ‘‘perfect health’’ (EQ-5D utility51) and 2) Gaussian modelling of EQ-5D utilities< 1. The utility during each grass pollen season was calculated as area under the curve. RESULTS: A total of 16,690 weekly and 137,792 daily EQ-5D observations were recorded over the trial period. The binomial model showed the daily RSS and RMS to be the two most important predictors of ‘‘perfect health’’ (RSS: OR50.729; p< 0.001; RMS: OR50.841; p< 0.001). The Gaussian model of subjects with ‘‘imperfect health’’ confirmed this correlation. Based on relationship the average annual utility was estimated to 2.2 QALD. CONCLUSIONS: In a clinical trial including subjects with grass pollen induced rhinoconjunctivitis, the daily RSS and RMS were found to be suitable predictors of the EQ-5D health utility. The findings confirm the beneficial impact of the SQ-standardised Timothy grass allergy immunotherapy tablet (75,000 SQ-T/2,800 BAU, ALK) on health utilities with a clinical relevant QALY gain.