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Efficacy and Safety of Ciclesonide (CIC) for the Treatment of Perennial Allergic Rhinitis (PAR)
Abstracts S259
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
The Effect of Smoking on the Expression of Various Cytokines in the Peripheral Blood Mononuclear Cells from Patients with Asthma and COPD Y. Cho1, E. Chun1, C. Park1, J. Lee1, S. Woo2; 1Internal Medicine, Ewha Womans University, Seoul, REPUBLIC OF KOREA, 2Micobiology, Ewha Womans University, Seoul, REPUBLIC OF KOREA. RATIONALE: Though cigarette smoking is common in asthmatic patients, the information about characteristics such as cytokine mediated airway inflammation of asthma and COPD, and the effect of smoking is less available. METHODS: Ten of severe degree of asthma with past heavy smoking history (Group A) and nine of COPD (Group B), eight of non-smoking asthma (Group C) and 6 of normal control (Group D) were included. We studied the expression of various cytokines mRNA(IL-2, IL-4, IL-5, Il-9, IL-10, IL-13, IL-12 and INF-) in the peripheral blood mononuclear cells (PBMCs) from groups of patients. Total RNA was isolated from PBMCs by using QIAamp RNA mini protocol (QIAGEN), and radioactive probe was prepared by using MultI-Probe Template set and vitro transcription kit. RESULTS: The levels of IL-9 in group A and C were significantly higher than those in groups B. There was no significant differences in the levels of IL-4 and IL-5, IL-10, IL-12 and IL-13 between three groups, however, the expression of INF- mRNA in Group B was prominent CONCLUSIONS: Both Th1 and Th2 cytokines seems to have roles in both COPD and asthmatic airway inflammation. Significant high levels of IL-9 from asthmatics suggests that IL-9 may be used as a new inflammatory marker of asthma independent of smoking history.
1002
Effects of Coadministration of Intranasal Ciclesonide (CIC) and Inhaled Beclomethasone Dipropionate (BDP) on Cortisol Suppression P. H. Ratner1, M. A. Wingertzahn2, N. Hall2, P. Darken2, T. Shah2; 1Sylvana Research Associates, San Antonio, TX, 2Altana Pharma, Florham Park, NJ. RATIONALE: Although intranasal corticosteroids (INCS) typically have negligible effects on cortisol levels when administered as monotherapy,
1003
increased steroid burden during coadministration with inhaled corticosteroids (ICS) might enhance cortisol suppression over that seen with ICS alone. Therefore, we evaluated the safety of a new INCS, CIC, when coadministered with an ICS, HFA-BDP, in adults with perennial allergic rhinitis. METHODS: After a 10-day run-in period with inhaled HFA-BDP 320 g twice daily (BID) and placebo nasal spray once daily (QD), 111 patients were randomized to receive intranasal CIC 200 g (n=56) or placebo (n=55) QD in addition to HFA-BDP 320 g BID for 43 days. Dexamethasone was administered as an active control on the last treatment day. Twenty-four hour plasma and urinary cortisol levels were assessed on the first and last days of run-in and at the end of treatment (before and after dexamethasone). RESULTS: Plasma cortisol area under the concentration versus time curve from 0 to 24 hours (AUC0-24h) was reduced by 67.8 g•h/dL on average during the HFA-BDP run-in period from a mean baseline level of 200.1 g•h/dL (p<0.001). During the treatment period, mean plasma cortisol AUC0-24h was similar between CIC and placebo (95% CI for treatment difference: -27.2, 12.1). After dexamethasone administration, mean plasma cortisol AUC0-24h decreased 65.1 g•h/dL on average (p<0.001), demonstrating that further suppression was possible. CONCLUSIONS: There were no additive inhibitory effects on cortisol compared to placebo when CIC was concomitantly administered with HFA-BDP, indicating that CIC can be used in conjunction with ICS without risk of increased cortisol suppression. Funding: Altana Pharma Efficacy and Safety of Ciclesonide (CIC) for the Treatment of Perennial Allergic Rhinitis (PAR) E. O. Meltzer1, S. Kunjibettu2, N. Hall2, W. Berger3, C. LaForce4; 1Allergy & Asthma Medical Group & Research Center, San Diego, CA, 2Altana Pharma, Florham Park, NJ, 3Allergy and Asthma Associates, Mission Viejo, CA, 4Clinical Professor of Pediatrics, University of North Carolina School of Medicine, Raleigh, NC. RATIONALE: Ciclesonide is a new corticosteroid under investigation for the treatment of allergic rhinitis. Study objectives were to demonstrate the efficacy of intranasal CIC 200 g once daily (OD) in the treatment of PAR, and to assess quality-of-life effects and safety. METHODS: In a phase III, multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents (n = 471) with a 2year history of PAR received intranasal administration of CIC 200 g (2 sprays per nostril) or placebo OD for 6 weeks. Patient-assessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and quality of life as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were evaluated. RESULTS: Ciclesonide significantly reduced the average am and pm reflective TNSS compared with placebo after 6 weeks of treatment (p < 0.001). Additionally, ciclesonide significantly reduced the average am and pm instantaneous TNSS after 6 weeks of treatment (p = 0.001). At endpoint, a greater decrease from baseline was observed in the PANS for the CIC group (p = 0.051 versus placebo). An appreciable improvement in the combined RQLQ scores at endpoint was also observed in patients treated with CIC compared with placebo (p = 0.011). The frequency of adverse events was similar among patients treated with CIC or placebo. CONCLUSIONS: Ciclesonide administered intranasally was significantly superior to placebo in relieving nasal symptoms and provided appreciable improvement in health-related quality of life in adult and adolescent patients with PAR. Ciclesonide was also well tolerated with a safety profile that was comparable with placebo. Funding: Altana
1004
MONDAY
Responses to Methacholine, Histamine and Osmotic Stimuli after Treatment with Interleukin-13 or Propranolol in Balb/c Versus CFW Mice N. Qutna, R. Townley; Dept of Medicine - Allergy Division, Creighton University Allergy, Omaha, NE. RATIONALE: IL-13 induces airway hyperresponsiveness (AHR) to MCh. We tested the hypothesis that the effect of IL-13 is not limited to MCh, and not exclusive to Balb/c mouse strain. METHODS: AHR to MCh induced by IL-13 was determined in Balb/c and CFW mice by body plethysmography and the provocative concentration causing a 200% increase in Penh (PC200). We compared this response to MCh with the response to osmotic stimuli with inhalation or 4.5% saline or H20 and histamine in Balb/c and in CFW strain with and without propranolol. We also measured the degree of drop in body temperature or death. RESULTS: IL-13 induces AHR to MCh in CFW and Balb/c mice to a similar degree. In CFW mice propranolol 50gm ip induced sensitivity to histamine ip (0.62mg) by drop in body temperature from 37.7° C to below 35.0°C and subsequent death in all mice. However, histamine alone did not cause death or a drop in temperature. Histamine inhalation alone had no effect on Penh in either strain. In Balb/c mice propranolol resulted in death in only 1/8 mice after the same dose of histamine as in CFW mice. CONCLUSIONS: CFW mice were sensitized to histamine by propranolol in contrast to Balb/c mice IL-13 did not induce sensitivity to osmotic stimuli in Balb/c mice. IL-13 induced sensitivity MCh in both strains of mice. Funding: Creighton University
1001
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
The Effect of Smoking on the Expression of Various Cytokines in the Peripheral Blood Mononuclear Cells from Patients with Asthma and COPD Y. Cho1, E. Chun1, C. Park1, J. Lee1, S. Woo2; 1Internal Medicine, Ewha Womans University, Seoul, REPUBLIC OF KOREA, 2Micobiology, Ewha Womans University, Seoul, REPUBLIC OF KOREA. RATIONALE: Though cigarette smoking is common in asthmatic patients, the information about characteristics such as cytokine mediated airway inflammation of asthma and COPD, and the effect of smoking is less available. METHODS: Ten of severe degree of asthma with past heavy smoking history (Group A) and nine of COPD (Group B), eight of non-smoking asthma (Group C) and 6 of normal control (Group D) were included. We studied the expression of various cytokines mRNA(IL-2, IL-4, IL-5, Il-9, IL-10, IL-13, IL-12 and INF-) in the peripheral blood mononuclear cells (PBMCs) from groups of patients. Total RNA was isolated from PBMCs by using QIAamp RNA mini protocol (QIAGEN), and radioactive probe was prepared by using MultI-Probe Template set and vitro transcription kit. RESULTS: The levels of IL-9 in group A and C were significantly higher than those in groups B. There was no significant differences in the levels of IL-4 and IL-5, IL-10, IL-12 and IL-13 between three groups, however, the expression of INF- mRNA in Group B was prominent CONCLUSIONS: Both Th1 and Th2 cytokines seems to have roles in both COPD and asthmatic airway inflammation. Significant high levels of IL-9 from asthmatics suggests that IL-9 may be used as a new inflammatory marker of asthma independent of smoking history.
1002
Effects of Coadministration of Intranasal Ciclesonide (CIC) and Inhaled Beclomethasone Dipropionate (BDP) on Cortisol Suppression P. H. Ratner1, M. A. Wingertzahn2, N. Hall2, P. Darken2, T. Shah2; 1Sylvana Research Associates, San Antonio, TX, 2Altana Pharma, Florham Park, NJ. RATIONALE: Although intranasal corticosteroids (INCS) typically have negligible effects on cortisol levels when administered as monotherapy,
1003
increased steroid burden during coadministration with inhaled corticosteroids (ICS) might enhance cortisol suppression over that seen with ICS alone. Therefore, we evaluated the safety of a new INCS, CIC, when coadministered with an ICS, HFA-BDP, in adults with perennial allergic rhinitis. METHODS: After a 10-day run-in period with inhaled HFA-BDP 320 g twice daily (BID) and placebo nasal spray once daily (QD), 111 patients were randomized to receive intranasal CIC 200 g (n=56) or placebo (n=55) QD in addition to HFA-BDP 320 g BID for 43 days. Dexamethasone was administered as an active control on the last treatment day. Twenty-four hour plasma and urinary cortisol levels were assessed on the first and last days of run-in and at the end of treatment (before and after dexamethasone). RESULTS: Plasma cortisol area under the concentration versus time curve from 0 to 24 hours (AUC0-24h) was reduced by 67.8 g•h/dL on average during the HFA-BDP run-in period from a mean baseline level of 200.1 g•h/dL (p<0.001). During the treatment period, mean plasma cortisol AUC0-24h was similar between CIC and placebo (95% CI for treatment difference: -27.2, 12.1). After dexamethasone administration, mean plasma cortisol AUC0-24h decreased 65.1 g•h/dL on average (p<0.001), demonstrating that further suppression was possible. CONCLUSIONS: There were no additive inhibitory effects on cortisol compared to placebo when CIC was concomitantly administered with HFA-BDP, indicating that CIC can be used in conjunction with ICS without risk of increased cortisol suppression. Funding: Altana Pharma Efficacy and Safety of Ciclesonide (CIC) for the Treatment of Perennial Allergic Rhinitis (PAR) E. O. Meltzer1, S. Kunjibettu2, N. Hall2, W. Berger3, C. LaForce4; 1Allergy & Asthma Medical Group & Research Center, San Diego, CA, 2Altana Pharma, Florham Park, NJ, 3Allergy and Asthma Associates, Mission Viejo, CA, 4Clinical Professor of Pediatrics, University of North Carolina School of Medicine, Raleigh, NC. RATIONALE: Ciclesonide is a new corticosteroid under investigation for the treatment of allergic rhinitis. Study objectives were to demonstrate the efficacy of intranasal CIC 200 g once daily (OD) in the treatment of PAR, and to assess quality-of-life effects and safety. METHODS: In a phase III, multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents (n = 471) with a 2year history of PAR received intranasal administration of CIC 200 g (2 sprays per nostril) or placebo OD for 6 weeks. Patient-assessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and quality of life as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were evaluated. RESULTS: Ciclesonide significantly reduced the average am and pm reflective TNSS compared with placebo after 6 weeks of treatment (p < 0.001). Additionally, ciclesonide significantly reduced the average am and pm instantaneous TNSS after 6 weeks of treatment (p = 0.001). At endpoint, a greater decrease from baseline was observed in the PANS for the CIC group (p = 0.051 versus placebo). An appreciable improvement in the combined RQLQ scores at endpoint was also observed in patients treated with CIC compared with placebo (p = 0.011). The frequency of adverse events was similar among patients treated with CIC or placebo. CONCLUSIONS: Ciclesonide administered intranasally was significantly superior to placebo in relieving nasal symptoms and provided appreciable improvement in health-related quality of life in adult and adolescent patients with PAR. Ciclesonide was also well tolerated with a safety profile that was comparable with placebo. Funding: Altana
1004
MONDAY
Responses to Methacholine, Histamine and Osmotic Stimuli after Treatment with Interleukin-13 or Propranolol in Balb/c Versus CFW Mice N. Qutna, R. Townley; Dept of Medicine - Allergy Division, Creighton University Allergy, Omaha, NE. RATIONALE: IL-13 induces airway hyperresponsiveness (AHR) to MCh. We tested the hypothesis that the effect of IL-13 is not limited to MCh, and not exclusive to Balb/c mouse strain. METHODS: AHR to MCh induced by IL-13 was determined in Balb/c and CFW mice by body plethysmography and the provocative concentration causing a 200% increase in Penh (PC200). We compared this response to MCh with the response to osmotic stimuli with inhalation or 4.5% saline or H20 and histamine in Balb/c and in CFW strain with and without propranolol. We also measured the degree of drop in body temperature or death. RESULTS: IL-13 induces AHR to MCh in CFW and Balb/c mice to a similar degree. In CFW mice propranolol 50gm ip induced sensitivity to histamine ip (0.62mg) by drop in body temperature from 37.7° C to below 35.0°C and subsequent death in all mice. However, histamine alone did not cause death or a drop in temperature. Histamine inhalation alone had no effect on Penh in either strain. In Balb/c mice propranolol resulted in death in only 1/8 mice after the same dose of histamine as in CFW mice. CONCLUSIONS: CFW mice were sensitized to histamine by propranolol in contrast to Balb/c mice IL-13 did not induce sensitivity to osmotic stimuli in Balb/c mice. IL-13 induced sensitivity MCh in both strains of mice. Funding: Creighton University
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