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Improvements in the Ratio of Forced Expiratory Volume in One Second to Forced Vital Capacity in Asthmatic Children Receiving Inhaled Mometasone Furoate
AB68 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
SUNDAY
266
Improvements in the Ratio of Forced Expiratory Volume in One Second to Forced Vital Capacity in Asthmatic Children Receiving Inhaled Mometasone Furoate H. Milgrom1, E. O. Meltzer2, W. E. Berger3; 1National Jewish Health, Denver, CO, 2Allergy and Asthma Medical Group and Research Center, San Diego, CA, 3Allergy and Asthma Associates of Southern California, Mission Viejo, CA. RATIONALE: The ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) may be more sensitive than FEV1 alone as an indicator of pediatric asthma severity. An FEV1/FVC >80% indicates wellcontrolled asthma in children aged 5-11 years. The beneficial effects of inhaled mometasone furoate (MF) on many asthma control measures in children have been reported previously; the current analysis expanded on these analyses to evaluate FEV1/FVC. METHODS: Data from three phase III clinical efficacy and safety studies in children aged 4-11 years with mild persistent asthma were pooled to analyze the effects of MF on FEV1/FVC over time. Patients (N5901) were randomized to 12 weeks of treatment with MF 100 or 200 mg/d or placebo. Changes from baseline in FEV1/FVC on day 4; weeks 1, 2, 4, 8, 12; and endpoint were analyzed by ANOVA. RESULTS: Baseline FEV1/FVC was >81% in the MF and placebo groups. Improvements from baseline in FEV1/FVC (up to 1%) occurred in the combined MF treatment group, whereas FEV1/FVC decreased with placebo (<0.1-2.9%), at all time points and endpoint. The differences between MF and placebo were significant at weeks 1, 4, 8, and 12, as well as endpoint (P<0.01). CONCLUSIONS: As an emerging sensitive measure of asthma severity in pediatric patients, this is the first report of FEV1/FVC data following MF 100 or 200 mg/d treatment compared with placebo. FEV1/FVC increased following MF, indicating improved asthma control over time, even in children who previously received inhaled corticosteroid therapy.
Pulmonary Function and Gender in Patients With Persistent Asthma Treated With Budesonide/Formoterol Pressurized Metered-Dose Inhaler (pMDI) C. D. O’Brien, T. Uryniak, J. Zangrilli; AstraZeneca LP, Wilmington, DE. RATIONALE: Because asthma prevalence and health care utilization are greater in women than men, we examined the response to budesonide/formoterol (BUD/FM) by gender in asthma patients. METHODS: Post hoc by-gender analyses evaluated predose FEV1 and 12-hour postdose FEV1 in 2 double-blind, 12-week studies (I: NCT00651651 [Clin Ther. 2007;29:823-843]; II: NCT00652002 [Drugs. 2006;66:2235-2254]). Patients 12 years with mild to moderate (I) or moderate to severe (II) persistent asthma underwent 2-week run-ins with placebo (I) or BUD pMDI 80mg 32 inhalations (160mg) bid (II) before randomization to 2 inhalations bid of BUD/FM pMDI (I: 80/4.5mg; II: 160/4.5mg), BUD pMDI (I: 80mg; II: 160mg), FM dry powder inhaler (4.5mg), or placebo. RESULTS: Absolute baseline FEV1 was lower in females (I range: 2.02.1L; II: 1.9-2.0L) than males (I: 2.7-2.8L; II: 2.6-2.8L); however, when corrected using % predicted FEV1, baseline values were consistent in females (I: 69.4%-71.0%; II: 67.3%-70.7%) and males (I: 70.9%-73.6%; II: 64.6%-68.6%). Similarly, mean percent changes from baseline to treatment average in predose FEV1 were consistent in females and males receiving BUD/FM (I: 17.0% vs 14.5%; II: 9.4% vs 9.3%), while absolute changes were lower in females (I: 0.3L vs 0.4L; II: 0.1L vs 0.2L). Baseline-adjusted mean 12-hour FEV1 (AUC) at week 2 (primary time point) improved in both genders receiving BUD/FM (I: 0.42L and 0.57L; II: 0.27L and 0.44L); values were lower in females, consistent with absolute changes in predose FEV1. CONCLUSIONS: In males and females receiving BUD/FM pMDI, pulmonary function improvements, using standard corrections for gender, were similar across a range of asthma severity.
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269
Adverse Effects Associated with Leukotriene Antagonist Therapy D. P. Gadde1, P. S. Creticos2, D. E. Beakes1, P. L. Dauby1, L. A. Grooms1, D. Abeel1, J. Gadde1; 1Allergy and Asthma Specialists, Fairfax, VA, 2 Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Leukotriene receptor antagonists (LTRa) have become a mainstay in the treatment of allergic rhinitis/asthma. Recent reports have cited the potential neuropsychiatric disturbances observed in patients (pts) receiving this medicine [FDA healthcare professional update; June, 2009]. In a metropolitan private practice, we identify 20 pts with adverse effects that correlate with use of montelukast (MK). METHODS: We reviewed 2700 current pts in this practice and captured the self-reported adverse effects related to usage of MK. The demographic characteristics and descriptive statistics were tabulated for this patient population. RESULTS: Of these 2700 pts, 814(30%) used MK during the period of observation(July 2006-August 2009). Of the 20 pts [male:11; female:9; age:3-62 years(mean:16 yr; median:8 yr)] that self-reported adverse effects on MK, treatment duration ranged from 0.5 wks-8 years [mn:14 months(mo); med:7mo](<1 mo:3 pts;1-3mo:5pts;3-6mo:1pt;6-12mo:6pts; >1 year:5pts). Neuropsychiatric disturbances described were: a]behavior disturbances: aggression (6) anger (5) agitation (1) hyperactivity (4) emotional lability (6) misbehaving (1); b]sleep disturbances: insomnia (5) hallucinations (1) vivid dreams: (1) night terrors (1) screaming at night (1); c] anxiety (4); d] depression: (2); e] sense of doom: (1). Seventeen of 20 pts had complete resolution of adverse events [< 1 week: 7 pts; <1 mo: 7 pts; 1-3 mo: 3 pts], 2 pts report improvement, and 1 pt still reports night terrors. CONCLUSION: This report notes the association between use of a LTRa and onset of new neuropsychiatric disturbances. This data emphasizes the need for post-marketing surveillance in pts placed on this class of drug and the need to carefully monitor neuropsychiatric outcomes in a systematic manner.
268
Prolonged Suppression of IgE Levels Associated with Allergic Bronchopulmonary Aspergillosis Treated with Omalizumab G. A. Bhargave, R. Y. Lin; St. Vincent Catholic Medical Center, New York, NY. RATIONALE: The ability to assess adequate IgE reductions in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. METHODS: Description of the clinical course and serial IgE levels in a patient with ABPA treated with omalizumab. RESULTS: A 54 year-old male with stage IVABPA had frequent hospitalizations, pulmonary scarring, and bronchiectasis. His IgE levels ranged between 9,541 to 10,200 IU/mL without systemic corticosteroid (SC) treatment, while nadir IgE levels on SC were as low as 189 IU/mL. In order to reduce SC exposure, omalizumab treatment was initiated when the IgE levels were adequately suppressed (<700 IU/mL) by SC. Using approved omalizumab dosing every two weeks, SC were fully withdrawn. While continuing on omalizumab, the measured IgE levels ranged between 586 and 688 IU/mL during a one-year interval, with the latter value obtained in the absence of any SC treatment for several months. During this oneyear time interval, the patient had markedly improved disease activity. His improved clinical state has continued to present time, six months later. Based on published omalizumab treatment-associated total/free IgE ratios of 2:1 to 5:1(Hamilton et al 2005), the estimated free IgE off SC was at most 344 IU/mL and at least 138 IU/mL. CONCLUSIONS: These data suggest that omalizumab can be beneficial in treating ABPA without sacrificing the ability to gauge IgE reductions. Furthermore, these findings raise the possibility that omalizumab plays a role in blunting the pathophysiological IgE increases that accompany ABPA exacerbations.
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
SUNDAY
266
Improvements in the Ratio of Forced Expiratory Volume in One Second to Forced Vital Capacity in Asthmatic Children Receiving Inhaled Mometasone Furoate H. Milgrom1, E. O. Meltzer2, W. E. Berger3; 1National Jewish Health, Denver, CO, 2Allergy and Asthma Medical Group and Research Center, San Diego, CA, 3Allergy and Asthma Associates of Southern California, Mission Viejo, CA. RATIONALE: The ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) may be more sensitive than FEV1 alone as an indicator of pediatric asthma severity. An FEV1/FVC >80% indicates wellcontrolled asthma in children aged 5-11 years. The beneficial effects of inhaled mometasone furoate (MF) on many asthma control measures in children have been reported previously; the current analysis expanded on these analyses to evaluate FEV1/FVC. METHODS: Data from three phase III clinical efficacy and safety studies in children aged 4-11 years with mild persistent asthma were pooled to analyze the effects of MF on FEV1/FVC over time. Patients (N5901) were randomized to 12 weeks of treatment with MF 100 or 200 mg/d or placebo. Changes from baseline in FEV1/FVC on day 4; weeks 1, 2, 4, 8, 12; and endpoint were analyzed by ANOVA. RESULTS: Baseline FEV1/FVC was >81% in the MF and placebo groups. Improvements from baseline in FEV1/FVC (up to 1%) occurred in the combined MF treatment group, whereas FEV1/FVC decreased with placebo (<0.1-2.9%), at all time points and endpoint. The differences between MF and placebo were significant at weeks 1, 4, 8, and 12, as well as endpoint (P<0.01). CONCLUSIONS: As an emerging sensitive measure of asthma severity in pediatric patients, this is the first report of FEV1/FVC data following MF 100 or 200 mg/d treatment compared with placebo. FEV1/FVC increased following MF, indicating improved asthma control over time, even in children who previously received inhaled corticosteroid therapy.
Pulmonary Function and Gender in Patients With Persistent Asthma Treated With Budesonide/Formoterol Pressurized Metered-Dose Inhaler (pMDI) C. D. O’Brien, T. Uryniak, J. Zangrilli; AstraZeneca LP, Wilmington, DE. RATIONALE: Because asthma prevalence and health care utilization are greater in women than men, we examined the response to budesonide/formoterol (BUD/FM) by gender in asthma patients. METHODS: Post hoc by-gender analyses evaluated predose FEV1 and 12-hour postdose FEV1 in 2 double-blind, 12-week studies (I: NCT00651651 [Clin Ther. 2007;29:823-843]; II: NCT00652002 [Drugs. 2006;66:2235-2254]). Patients 12 years with mild to moderate (I) or moderate to severe (II) persistent asthma underwent 2-week run-ins with placebo (I) or BUD pMDI 80mg 32 inhalations (160mg) bid (II) before randomization to 2 inhalations bid of BUD/FM pMDI (I: 80/4.5mg; II: 160/4.5mg), BUD pMDI (I: 80mg; II: 160mg), FM dry powder inhaler (4.5mg), or placebo. RESULTS: Absolute baseline FEV1 was lower in females (I range: 2.02.1L; II: 1.9-2.0L) than males (I: 2.7-2.8L; II: 2.6-2.8L); however, when corrected using % predicted FEV1, baseline values were consistent in females (I: 69.4%-71.0%; II: 67.3%-70.7%) and males (I: 70.9%-73.6%; II: 64.6%-68.6%). Similarly, mean percent changes from baseline to treatment average in predose FEV1 were consistent in females and males receiving BUD/FM (I: 17.0% vs 14.5%; II: 9.4% vs 9.3%), while absolute changes were lower in females (I: 0.3L vs 0.4L; II: 0.1L vs 0.2L). Baseline-adjusted mean 12-hour FEV1 (AUC) at week 2 (primary time point) improved in both genders receiving BUD/FM (I: 0.42L and 0.57L; II: 0.27L and 0.44L); values were lower in females, consistent with absolute changes in predose FEV1. CONCLUSIONS: In males and females receiving BUD/FM pMDI, pulmonary function improvements, using standard corrections for gender, were similar across a range of asthma severity.
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269
Adverse Effects Associated with Leukotriene Antagonist Therapy D. P. Gadde1, P. S. Creticos2, D. E. Beakes1, P. L. Dauby1, L. A. Grooms1, D. Abeel1, J. Gadde1; 1Allergy and Asthma Specialists, Fairfax, VA, 2 Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Leukotriene receptor antagonists (LTRa) have become a mainstay in the treatment of allergic rhinitis/asthma. Recent reports have cited the potential neuropsychiatric disturbances observed in patients (pts) receiving this medicine [FDA healthcare professional update; June, 2009]. In a metropolitan private practice, we identify 20 pts with adverse effects that correlate with use of montelukast (MK). METHODS: We reviewed 2700 current pts in this practice and captured the self-reported adverse effects related to usage of MK. The demographic characteristics and descriptive statistics were tabulated for this patient population. RESULTS: Of these 2700 pts, 814(30%) used MK during the period of observation(July 2006-August 2009). Of the 20 pts [male:11; female:9; age:3-62 years(mean:16 yr; median:8 yr)] that self-reported adverse effects on MK, treatment duration ranged from 0.5 wks-8 years [mn:14 months(mo); med:7mo](<1 mo:3 pts;1-3mo:5pts;3-6mo:1pt;6-12mo:6pts; >1 year:5pts). Neuropsychiatric disturbances described were: a]behavior disturbances: aggression (6) anger (5) agitation (1) hyperactivity (4) emotional lability (6) misbehaving (1); b]sleep disturbances: insomnia (5) hallucinations (1) vivid dreams: (1) night terrors (1) screaming at night (1); c] anxiety (4); d] depression: (2); e] sense of doom: (1). Seventeen of 20 pts had complete resolution of adverse events [< 1 week: 7 pts; <1 mo: 7 pts; 1-3 mo: 3 pts], 2 pts report improvement, and 1 pt still reports night terrors. CONCLUSION: This report notes the association between use of a LTRa and onset of new neuropsychiatric disturbances. This data emphasizes the need for post-marketing surveillance in pts placed on this class of drug and the need to carefully monitor neuropsychiatric outcomes in a systematic manner.
268
Prolonged Suppression of IgE Levels Associated with Allergic Bronchopulmonary Aspergillosis Treated with Omalizumab G. A. Bhargave, R. Y. Lin; St. Vincent Catholic Medical Center, New York, NY. RATIONALE: The ability to assess adequate IgE reductions in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. METHODS: Description of the clinical course and serial IgE levels in a patient with ABPA treated with omalizumab. RESULTS: A 54 year-old male with stage IVABPA had frequent hospitalizations, pulmonary scarring, and bronchiectasis. His IgE levels ranged between 9,541 to 10,200 IU/mL without systemic corticosteroid (SC) treatment, while nadir IgE levels on SC were as low as 189 IU/mL. In order to reduce SC exposure, omalizumab treatment was initiated when the IgE levels were adequately suppressed (<700 IU/mL) by SC. Using approved omalizumab dosing every two weeks, SC were fully withdrawn. While continuing on omalizumab, the measured IgE levels ranged between 586 and 688 IU/mL during a one-year interval, with the latter value obtained in the absence of any SC treatment for several months. During this oneyear time interval, the patient had markedly improved disease activity. His improved clinical state has continued to present time, six months later. Based on published omalizumab treatment-associated total/free IgE ratios of 2:1 to 5:1(Hamilton et al 2005), the estimated free IgE off SC was at most 344 IU/mL and at least 138 IU/mL. CONCLUSIONS: These data suggest that omalizumab can be beneficial in treating ABPA without sacrificing the ability to gauge IgE reductions. Furthermore, these findings raise the possibility that omalizumab plays a role in blunting the pathophysiological IgE increases that accompany ABPA exacerbations.