- Email: [email protected]
Ciclesonide, a new inhaled corticosteroid, significantly improves asthma-related quality of life in patients with severe, persistent asthma
S210 Abstracts
Effect of Ciclesonide 40 g and 80 g on Early and Late Asthmatic Reaction, and Sputum Eosinophils After Allergen Challenge in Patients With Mild Asthma G. M. Gauvreau1, R. M. Watson1, D. S. Postma2, J. G. R. de Monchy3, F. Deschesnes3, L. Boulet3; 1McMaster University, Hamilton, ON, CANADA, 2University Hospital Hanzeplein, Groningen, THE NETHERLANDS, 3Laval University, Québec City, PQ, CANADA. RATIONALE: Inhaled corticosteroids decrease early (EAR) and late asthmatic reactions (LAR), and reduce allergen-induced sputum eosinophils and serum eosinophil cationic protein (ECP) after allergen challenge. In this study, the effect of ciclesonide, a novel inhaled corticosteroid, on EAR, LAR, sputum eosinophils, and ECP was examined after allergen challenge. METHODS: In a randomized, double-blind, 3-period cross-over study, 22 patients (age 18 to 60 y) with mild asthma and documented EAR and LAR received once-daily in the morning ciclesonide 40 and 80 g (exactuator HFA-MDI; equivalent to 50 and 100 g ex-valve), and placebo. Each 1-week treatment period was separated by a washout period (≥ 3 weeks). EAR and LAR lung function after allergen challenge was examined on Day 6 of each treatment period. Sputum eosinophils were determined before (Day 5) and after (Day 7) allergen challenge; serum ECP was measured on Day 7. RESULTS: Ciclesonide 80 g was superior to placebo with respect to changes in EAR (p = 0.0257), LAR (p = 0.0001), sputum eosinophils (p = 0.0057), and serum ECP (p = 0.0238). For ciclesonide 40 g, superiority over placebo was shown for LAR (p = 0.0005) and sputum eosinophils (p = 0.0006). There was no significant difference between the two ciclesonide doses; however, there was a trend towards a dose-response effect. CONCLUSIONS: In patients with mild asthma, ciclesonide 40 g significantly decreased LAR and sputum eosinophils; ciclesonide 80 g, in addition, significantly reduced EAR and serum ECP. Thus, these results suggest that the minimal effective dose of ciclesonide is 80 g. Funding: ALTANA Pharma AG
834
High Dose Corticosteroid Exposure in Adult Members of a Large Health Maintenance Organization M. Che1, B. Ettinger2, M. Nguyen3; 1Kaiser Permanente, Vacaville, CA, 2Kaiser Permanente Division of Research, Oakland, CA, 3Kaiser Permanente, Oakland, CA. RATIONALE: To identify patients exposed to high doses of oral, and/or inhaled corticosteroids, and to determine what proportions received osteoporosis interventions to prevent future fractures. METHODS: We examined use of high dose corticosteroids and osteoporosis interventions among members of Kaiser Foundation Health Plan of Northern California (KFHP) who were aged ≥20 years, by examining electronic databases in 2002. Algorithms were developed to quantitate high cumulative exposure to oral alone, inhaled alone, and combinations of these drugs. RESULTS: Overall, high dose exposure to corticosteroid drugs was found in 18,737 (0.8%) of members (7757 (41%) men, 10,980 (59%) women); prevalence increased with age, from 0.4% in those aged 20-49 years to 2% in those 75 years and older. Of high dose users, 72% used only oral, 15% used only inhaled, and 13% used combinations of oral and inhaled corticosteroids. Bone densities were performed in 9% and 4% of men and 27% and 23% of women exposed to oral and inhaled corticosteroids, respectively. Prescriptions of drugs used to treat osteoporosis were filled by 6% and 1% of men and 11% and 5% of women receiving oral and inhaled corticosteroids. CONCLUSIONS: We conclude that about 1 in 125 people aged 20 years and older are exposed to high doses of corticosteroids; oral exposure is 3 times more common than inhaled. Most exposed patients do not receive osteoporosis intervention. Identification of high dose oral and inhaled corticosteroid users is feasible using prescription databases, and should allow focused interventions to reduce the risk of osteoporotic fracture. Funding: Merck
835
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Ciclesonide, a New Inhaled Corticosteroid, Significantly Improves Asthma-Related Quality of Life in Patients With Severe, Persistent Asthma D. Bernstein1, R. Nathan2, D. Ledford3, E. Ledoux4, A. Pedinoff5, C. Crivera6, J. Williams6, S. Kundu6, J. Fish6, D. Banerji6; 1Bernstein Clinical Research Center, Cincinnati, OH, 2Asthma and Allergy Associates PC, Colorado Springs, CO, 3University of South Florida, Tampa, FL, 4Pulmonary Consultants, Tacoma, WA, 5Princeton Center for Clinical Research, Princeton, NJ, 6Aventis Pharmaceuticals, Bridgewater, NJ. RATIONALE: Quality of life (QoL) decreases with increasing asthma severity. Utilization of the Juniper Asthma Quality of Life Questionnaire (AQLQ) provides a comprehensive means of assessing QoL in patients with severe asthma. The aim of this study was to evaluate the effect of ciclesonide (CIC), delivered via a hydrofluoroalkane metered-dose inhaler (MDI), on QoL in patients with severe asthma. METHODS: 531 patients with severe asthma (≥12 years; FEV1 40-65% predicted) were enrolled in a Phase III, 12-week, multicenter, doubleblind, parallel-group, placebo (PBO)-controlled trial. Patients were randomized to receive CIC 160 or 320 g bid or fluticasone propionate (FP) chlorofluorocarbon MDI 440 g bid (ex-actuator doses) or PBO. Overall AQLQ and individual domain scores (activity limitation, symptoms, emotional function and exposure to environmental stimuli) were recorded at baseline and at weeks 4 and 12. A minimally important difference (MID) of ≥0.5 was required for each domain or overall AQLQ score to reflect clinically important changes in QoL. RESULTS: Clinically significant (P<0.0001) improvements from baseline to week 12 in overall AQLQ score were observed in CIC and FP (CIC320, 0.61; CIC640, 0.65; FP880, 0.91) versus PBO. Results from the four individual domain scores were also significantly different for all CIC and FP groups versus PBO (P=0.004). Change from baseline to week 12 in overall AQLQ score of ≥0.5 MID was noted in patients in CIC and FP groups (CIC320, 42.5%; CIC640, 43%; and FP880, 58.8%) versus PBO (26.8%). CONCLUSIONS: Ciclesonide treatment leads to clinically meaningful improvements in quality of life in patients with severe asthma. Funding: Aventis and Altana Pharma
836
TUESDAY
A Novel Inhaled Corticosteroid Ciclesonide Significantly Improves Quality of Life in Patients With Mild-to-Moderate Asthma A. Nayak1, B. L. Charous2, A. Finn3, W. Lumry4, C. Crivera5, J. Williams5, S. Kundu5, J. Fish5, D. Banerji5; 1Sneeze, Wheeze and Itch Associates, Normal, IL, 2Milwaukee Medical Clinic Advance Healthcare, Milwaukee, WI, 3National Allergy, Asthma and Urticaria Centers, Charleston, SC, 4Allergy & Asthma Research Associates, Dallas, TX, 5Aventis Pharmaceuticals, Bridgewater, NJ. RATIONALE: Unlike conventional indices of asthma progression measuring lung function parameters, quality-of-life (QoL) assessments provide data on patients’ daily physical, emotional and social difficulties. The effect of ciclesonide (CIC), administered via a hydrofluoroalkane metered-dose inhaler, on QoL was evaluated in a combined analysis of two identical, Phase III, 12-week, multicenter, double-blind, randomized, parallel-group, placebo (PBO)-controlled trials. QoL was assessed using the Juniper Asthma Quality of Life Questionnaire (AQLQ). METHODS: A total of 1015 patients with mild-to-moderate asthma (≥12 years; FEV1 60-85% predicted) were randomized to receive PBO or CIC 80, 160 or 320 g once daily (ex-actuator doses). The overall AQLQ score and individual domain scores (activity limitation, symptoms, emotional function and exposure to environmental stimuli) were recorded at baseline and at weeks 4 and 12. A minimally important difference (MID) of ≥0.5 was required for each domain or overall AQLQ score to reflect clinically important changes in QoL. RESULTS: A significant improvement (P<0.0001) in overall AQLQ score was observed for all CIC groups (CIC80, 0.36; CIC160, 0.47; CIC320, 0.55) versus PBO, from baseline to week 12. A similar trend was observed for all four individual domain scores, except the environmental
837
Effect of Ciclesonide 40 g and 80 g on Early and Late Asthmatic Reaction, and Sputum Eosinophils After Allergen Challenge in Patients With Mild Asthma G. M. Gauvreau1, R. M. Watson1, D. S. Postma2, J. G. R. de Monchy3, F. Deschesnes3, L. Boulet3; 1McMaster University, Hamilton, ON, CANADA, 2University Hospital Hanzeplein, Groningen, THE NETHERLANDS, 3Laval University, Québec City, PQ, CANADA. RATIONALE: Inhaled corticosteroids decrease early (EAR) and late asthmatic reactions (LAR), and reduce allergen-induced sputum eosinophils and serum eosinophil cationic protein (ECP) after allergen challenge. In this study, the effect of ciclesonide, a novel inhaled corticosteroid, on EAR, LAR, sputum eosinophils, and ECP was examined after allergen challenge. METHODS: In a randomized, double-blind, 3-period cross-over study, 22 patients (age 18 to 60 y) with mild asthma and documented EAR and LAR received once-daily in the morning ciclesonide 40 and 80 g (exactuator HFA-MDI; equivalent to 50 and 100 g ex-valve), and placebo. Each 1-week treatment period was separated by a washout period (≥ 3 weeks). EAR and LAR lung function after allergen challenge was examined on Day 6 of each treatment period. Sputum eosinophils were determined before (Day 5) and after (Day 7) allergen challenge; serum ECP was measured on Day 7. RESULTS: Ciclesonide 80 g was superior to placebo with respect to changes in EAR (p = 0.0257), LAR (p = 0.0001), sputum eosinophils (p = 0.0057), and serum ECP (p = 0.0238). For ciclesonide 40 g, superiority over placebo was shown for LAR (p = 0.0005) and sputum eosinophils (p = 0.0006). There was no significant difference between the two ciclesonide doses; however, there was a trend towards a dose-response effect. CONCLUSIONS: In patients with mild asthma, ciclesonide 40 g significantly decreased LAR and sputum eosinophils; ciclesonide 80 g, in addition, significantly reduced EAR and serum ECP. Thus, these results suggest that the minimal effective dose of ciclesonide is 80 g. Funding: ALTANA Pharma AG
834
High Dose Corticosteroid Exposure in Adult Members of a Large Health Maintenance Organization M. Che1, B. Ettinger2, M. Nguyen3; 1Kaiser Permanente, Vacaville, CA, 2Kaiser Permanente Division of Research, Oakland, CA, 3Kaiser Permanente, Oakland, CA. RATIONALE: To identify patients exposed to high doses of oral, and/or inhaled corticosteroids, and to determine what proportions received osteoporosis interventions to prevent future fractures. METHODS: We examined use of high dose corticosteroids and osteoporosis interventions among members of Kaiser Foundation Health Plan of Northern California (KFHP) who were aged ≥20 years, by examining electronic databases in 2002. Algorithms were developed to quantitate high cumulative exposure to oral alone, inhaled alone, and combinations of these drugs. RESULTS: Overall, high dose exposure to corticosteroid drugs was found in 18,737 (0.8%) of members (7757 (41%) men, 10,980 (59%) women); prevalence increased with age, from 0.4% in those aged 20-49 years to 2% in those 75 years and older. Of high dose users, 72% used only oral, 15% used only inhaled, and 13% used combinations of oral and inhaled corticosteroids. Bone densities were performed in 9% and 4% of men and 27% and 23% of women exposed to oral and inhaled corticosteroids, respectively. Prescriptions of drugs used to treat osteoporosis were filled by 6% and 1% of men and 11% and 5% of women receiving oral and inhaled corticosteroids. CONCLUSIONS: We conclude that about 1 in 125 people aged 20 years and older are exposed to high doses of corticosteroids; oral exposure is 3 times more common than inhaled. Most exposed patients do not receive osteoporosis intervention. Identification of high dose oral and inhaled corticosteroid users is feasible using prescription databases, and should allow focused interventions to reduce the risk of osteoporotic fracture. Funding: Merck
835
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Ciclesonide, a New Inhaled Corticosteroid, Significantly Improves Asthma-Related Quality of Life in Patients With Severe, Persistent Asthma D. Bernstein1, R. Nathan2, D. Ledford3, E. Ledoux4, A. Pedinoff5, C. Crivera6, J. Williams6, S. Kundu6, J. Fish6, D. Banerji6; 1Bernstein Clinical Research Center, Cincinnati, OH, 2Asthma and Allergy Associates PC, Colorado Springs, CO, 3University of South Florida, Tampa, FL, 4Pulmonary Consultants, Tacoma, WA, 5Princeton Center for Clinical Research, Princeton, NJ, 6Aventis Pharmaceuticals, Bridgewater, NJ. RATIONALE: Quality of life (QoL) decreases with increasing asthma severity. Utilization of the Juniper Asthma Quality of Life Questionnaire (AQLQ) provides a comprehensive means of assessing QoL in patients with severe asthma. The aim of this study was to evaluate the effect of ciclesonide (CIC), delivered via a hydrofluoroalkane metered-dose inhaler (MDI), on QoL in patients with severe asthma. METHODS: 531 patients with severe asthma (≥12 years; FEV1 40-65% predicted) were enrolled in a Phase III, 12-week, multicenter, doubleblind, parallel-group, placebo (PBO)-controlled trial. Patients were randomized to receive CIC 160 or 320 g bid or fluticasone propionate (FP) chlorofluorocarbon MDI 440 g bid (ex-actuator doses) or PBO. Overall AQLQ and individual domain scores (activity limitation, symptoms, emotional function and exposure to environmental stimuli) were recorded at baseline and at weeks 4 and 12. A minimally important difference (MID) of ≥0.5 was required for each domain or overall AQLQ score to reflect clinically important changes in QoL. RESULTS: Clinically significant (P<0.0001) improvements from baseline to week 12 in overall AQLQ score were observed in CIC and FP (CIC320, 0.61; CIC640, 0.65; FP880, 0.91) versus PBO. Results from the four individual domain scores were also significantly different for all CIC and FP groups versus PBO (P=0.004). Change from baseline to week 12 in overall AQLQ score of ≥0.5 MID was noted in patients in CIC and FP groups (CIC320, 42.5%; CIC640, 43%; and FP880, 58.8%) versus PBO (26.8%). CONCLUSIONS: Ciclesonide treatment leads to clinically meaningful improvements in quality of life in patients with severe asthma. Funding: Aventis and Altana Pharma
836
TUESDAY
A Novel Inhaled Corticosteroid Ciclesonide Significantly Improves Quality of Life in Patients With Mild-to-Moderate Asthma A. Nayak1, B. L. Charous2, A. Finn3, W. Lumry4, C. Crivera5, J. Williams5, S. Kundu5, J. Fish5, D. Banerji5; 1Sneeze, Wheeze and Itch Associates, Normal, IL, 2Milwaukee Medical Clinic Advance Healthcare, Milwaukee, WI, 3National Allergy, Asthma and Urticaria Centers, Charleston, SC, 4Allergy & Asthma Research Associates, Dallas, TX, 5Aventis Pharmaceuticals, Bridgewater, NJ. RATIONALE: Unlike conventional indices of asthma progression measuring lung function parameters, quality-of-life (QoL) assessments provide data on patients’ daily physical, emotional and social difficulties. The effect of ciclesonide (CIC), administered via a hydrofluoroalkane metered-dose inhaler, on QoL was evaluated in a combined analysis of two identical, Phase III, 12-week, multicenter, double-blind, randomized, parallel-group, placebo (PBO)-controlled trials. QoL was assessed using the Juniper Asthma Quality of Life Questionnaire (AQLQ). METHODS: A total of 1015 patients with mild-to-moderate asthma (≥12 years; FEV1 60-85% predicted) were randomized to receive PBO or CIC 80, 160 or 320 g once daily (ex-actuator doses). The overall AQLQ score and individual domain scores (activity limitation, symptoms, emotional function and exposure to environmental stimuli) were recorded at baseline and at weeks 4 and 12. A minimally important difference (MID) of ≥0.5 was required for each domain or overall AQLQ score to reflect clinically important changes in QoL. RESULTS: A significant improvement (P<0.0001) in overall AQLQ score was observed for all CIC groups (CIC80, 0.36; CIC160, 0.47; CIC320, 0.55) versus PBO, from baseline to week 12. A similar trend was observed for all four individual domain scores, except the environmental
837