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Montelukast Is a Better Controller in Obese Atopic Asthmatics
AB210 Abstracts
683
Montelukast Is a Better Controller in Obese Atopic Asthmatics
Sherry Farzan, MD1, Sundas Khan, MD2, Claudia Elera2, Meredith Akerman, MS3; 1Departments of Pediatrics and Internal Medicine, Division of Allergy & Immunology, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY, 2Department of Medicine, North Shore LIJ Health System, Hofstra University School of Medicine, Manhasset, NY, 3Department of Biostatistics, Feinstein Institute of Medicine, North Shore - LIJ Health System, Hofstra University School of Medicine, Manhasset, NY. RATIONALE: The concomitant rise in the prevalence of asthma and obesity has suggested an association between the two. Two phenotypes of obesity-associated asthma exist; early-onset atopic and late-onset non-atopic asthma. Animal and human studies suggest involvement of leptin and leukotrienes in inflammatory pathways. We hypothesized that montelukast is a more effective controller of early-onset atopic asthma in overweight/obese (O) compared to normal (N) weight asthmatics. METHODS: Mild to moderate persistent early-onset asthmatics on inhaled corticosteroids (ICS) were randomized in a double-blind controlled manner to receive montelukast (M) or placebo (P). Treatment with M was compared to P at week 24 for the primary outcome measure, Asthma Control Test (ACT) scores, and secondary outcome measures (spirometric measures, exhaled nitric oxide, total ICS dose, serum leptin and urinary leukotriene E4). Mean difference was calculated as M group minus P group with corresponding 95% confidence intervals. RESULTS: The two treatment groups were comparable at baseline. At week 24, the O group, but not the N group, treated with M demonstrated a significantly higher ACT score than P (25.0 vs 15.7 respectively, p<0.01). ACT score differed significantly between M and P groups (24.5 vs 18.1 respectively, p<0.01), overall, but not for any other clinical or laboratory parameters assessed. There were no significant interactions between treatment group and weight subgroup for any parameters of interest. CONCLUSIONS: Montelukast is a more effective controller medication among obese atopic early-onset compared to normal weight asthmatics. These data underscore the need to elucidate the underlying mechanism and individualize the management of obesity-associated asthma.
684
Once-Daily Tiotropium RespimatÒ Add-on to at Least Ics Maintenance Therapy Demonstrates Improved Asthma Control in Patients with Symptomatic Asthma, Independent of Serum IgE or Blood Eosinophil Levels
MONDAY
Mark L. Vandewalker, MD1, Johann Christian Virchow, MD2, Thomas B. Casale, MD, FAAAAI3, Michael Engel, MD4, Petra MoroniZentgraf, MD4, Reinhold L€uhmann, PhD5, Ronald Dahl, MD6; 1Clinical Research of the Ozarks, Columbia, MO, 2University Clinic Rostock, Rostock, Germany, 3University of South Florida Morsani College of Medicine, Tampa, FL, 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, 5Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 6Odense University Hospital, Odense, Denmark. RATIONALE: Once-daily tiotropium RespimatÒ (tioR) add-on to at least ICS maintenance therapy has demonstrated asthma symptom control improvements in adults with moderate or severe symptomatic asthma, _ or >430mg/L (equivalent to 179.2 IU/L) and independent of serum IgE < _ or >0.63109/L (equivalent to 600/mL), in blood eosinophils < conventional subgroup analyses. We assessed whether improvements in asthma control were observed in modeling estimates across a continuous range of IgE and eosinophil values following tioR add-on therapy. METHODS: Four Phase III double-blind, placebo-controlled, parallel-group trials: PrimoTinA-asthmaÒ (23 48-week trials; NCT00776984/NCT00772538; n5912) tioR 5mg or placebo RespimatÒ _800mg budesonide or equivalent) + LABA; add-on to ICS (> (23 24-week trials; NCT01172808/ MezzoTinA-asthmaÒ
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
NCT01172821; n52100) tioR 5mg or 2.5mg or placebo add-on to ICS (400-800mg budesonide or equivalent). Patients had symptomatic asthma _4 weeks before screening; COPD was requiring at least ICS therapy for > excluded. Seven-question Asthma Control Questionnaire (ACQ-7) score is the mean of questions scored using a Likert scale. Post hoc logistic regression modeling analyses of ACQ-7 responder rate (percentage of _0.5) were performed patients with minimally important reduction of > across continuous ranges of IgE 2-2000mg/L and eosinophils 0.05-2.003109/L following tioR therapy. RESULTS: TioR consistently improved ACQ-7 responder rate, compared with placebo, across all IgE and eosinophil ranges (odds ratio >1), except tioR 2.5mg at the very lowest IgE and eosinophil values (MezzoTinA-asthmaÒ). CONCLUSIONS: Once-daily tiotropium RespimatÒ add-on to at least ICS improved asthma symptom control in patients with moderate or severe symptomatic asthma, across the range of IgE and eosinophil values, supporting findings from conventional subgroup analyses.
685
Feasibility of Using Treatment Response Thresholds for Lung Function and Asthma Symptom Variables As Indicators of Asthma Control in Patients with Moderate to Severe Asthma
David J. Slade1, Michael DePietro1, John Horton1, Donald P. Tashkin2, Bradley E. Chipps, MD3; 1AstraZeneca LP, Wilmington, DE, 2University of California, Los Angeles, CA, 3Capital Allergy & Respiratory Disease Center, Sacramento, CA. RATIONALE: Simple tools are needed in clinical practice for monitoring asthma control. METHODS: This post hoc analysis (12-week study; NCT00652002) in moderate-to-severe asthma patients assessed the relationship between loss of asthma control (defined as withdrawal due to predefined asthma event during the treatment period) and response thresholds for lung function and symptoms. Response thresholds were based on mean changes from _100-mL improvement in forced baseline during treatment period: > _30-L/min improvement in evening expiratory volume in 1 second (FEV1), > _0.5-point decrease in asthma symptom peak expiratory flow (PEF), and > score (4-point scale). Data were evaluated overall and by treatment (twice-daily budesonide [BUD]/formoterol [FM] pMDI 320/9mg [n5107], BUD pMDI 320mg [n593], FM DPI 9mg [n598], or placebo [n591]). RESULTS: Overall, loss of asthma control was considerably more likely among non-responders (threshold not achieved) versus responders (threshold achieved) based on FEV1 (32.7% [n572/220] vs 11.8% [20/ 169]), evening PEF (29.6% [89/301] vs 3.4% [3/87]), and asthma symptom score (27.9% [88/315] vs 5.4% [4/74]). These findings were consistent across treatments; however, loss of asthma control was less common with BUD/FM (nonresponders vs responders: FEV1 [15.4% vs 4.4%], PEF [14.0% vs 2.0%], symptoms [11.7% vs 0.0%]) and BUD (FEV1 [21.6% vs 11.9%]; PEF [19.4% vs 6.3%]; symptoms [18.2% vs 12.5%]) versus FM (FEV1 [43.3% vs 18.4%]; PEF [38.6% vs 6.7%]; symptoms [41.0% vs 5.0%] and placebo (FEV1 [41.4% vs 23.8%]; PEF [40.5% vs 0%]; symptoms [39.8% vs 12.5%]). CONCLUSIONS: Findings confirm the feasibility of using specific response thresholds in monitoring asthma control during initiation of treatment. Supported by AstraZeneca, LP.
683
Montelukast Is a Better Controller in Obese Atopic Asthmatics
Sherry Farzan, MD1, Sundas Khan, MD2, Claudia Elera2, Meredith Akerman, MS3; 1Departments of Pediatrics and Internal Medicine, Division of Allergy & Immunology, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY, 2Department of Medicine, North Shore LIJ Health System, Hofstra University School of Medicine, Manhasset, NY, 3Department of Biostatistics, Feinstein Institute of Medicine, North Shore - LIJ Health System, Hofstra University School of Medicine, Manhasset, NY. RATIONALE: The concomitant rise in the prevalence of asthma and obesity has suggested an association between the two. Two phenotypes of obesity-associated asthma exist; early-onset atopic and late-onset non-atopic asthma. Animal and human studies suggest involvement of leptin and leukotrienes in inflammatory pathways. We hypothesized that montelukast is a more effective controller of early-onset atopic asthma in overweight/obese (O) compared to normal (N) weight asthmatics. METHODS: Mild to moderate persistent early-onset asthmatics on inhaled corticosteroids (ICS) were randomized in a double-blind controlled manner to receive montelukast (M) or placebo (P). Treatment with M was compared to P at week 24 for the primary outcome measure, Asthma Control Test (ACT) scores, and secondary outcome measures (spirometric measures, exhaled nitric oxide, total ICS dose, serum leptin and urinary leukotriene E4). Mean difference was calculated as M group minus P group with corresponding 95% confidence intervals. RESULTS: The two treatment groups were comparable at baseline. At week 24, the O group, but not the N group, treated with M demonstrated a significantly higher ACT score than P (25.0 vs 15.7 respectively, p<0.01). ACT score differed significantly between M and P groups (24.5 vs 18.1 respectively, p<0.01), overall, but not for any other clinical or laboratory parameters assessed. There were no significant interactions between treatment group and weight subgroup for any parameters of interest. CONCLUSIONS: Montelukast is a more effective controller medication among obese atopic early-onset compared to normal weight asthmatics. These data underscore the need to elucidate the underlying mechanism and individualize the management of obesity-associated asthma.
684
Once-Daily Tiotropium RespimatÒ Add-on to at Least Ics Maintenance Therapy Demonstrates Improved Asthma Control in Patients with Symptomatic Asthma, Independent of Serum IgE or Blood Eosinophil Levels
MONDAY
Mark L. Vandewalker, MD1, Johann Christian Virchow, MD2, Thomas B. Casale, MD, FAAAAI3, Michael Engel, MD4, Petra MoroniZentgraf, MD4, Reinhold L€uhmann, PhD5, Ronald Dahl, MD6; 1Clinical Research of the Ozarks, Columbia, MO, 2University Clinic Rostock, Rostock, Germany, 3University of South Florida Morsani College of Medicine, Tampa, FL, 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, 5Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, 6Odense University Hospital, Odense, Denmark. RATIONALE: Once-daily tiotropium RespimatÒ (tioR) add-on to at least ICS maintenance therapy has demonstrated asthma symptom control improvements in adults with moderate or severe symptomatic asthma, _ or >430mg/L (equivalent to 179.2 IU/L) and independent of serum IgE < _ or >0.63109/L (equivalent to 600/mL), in blood eosinophils < conventional subgroup analyses. We assessed whether improvements in asthma control were observed in modeling estimates across a continuous range of IgE and eosinophil values following tioR add-on therapy. METHODS: Four Phase III double-blind, placebo-controlled, parallel-group trials: PrimoTinA-asthmaÒ (23 48-week trials; NCT00776984/NCT00772538; n5912) tioR 5mg or placebo RespimatÒ _800mg budesonide or equivalent) + LABA; add-on to ICS (> (23 24-week trials; NCT01172808/ MezzoTinA-asthmaÒ
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
NCT01172821; n52100) tioR 5mg or 2.5mg or placebo add-on to ICS (400-800mg budesonide or equivalent). Patients had symptomatic asthma _4 weeks before screening; COPD was requiring at least ICS therapy for > excluded. Seven-question Asthma Control Questionnaire (ACQ-7) score is the mean of questions scored using a Likert scale. Post hoc logistic regression modeling analyses of ACQ-7 responder rate (percentage of _0.5) were performed patients with minimally important reduction of > across continuous ranges of IgE 2-2000mg/L and eosinophils 0.05-2.003109/L following tioR therapy. RESULTS: TioR consistently improved ACQ-7 responder rate, compared with placebo, across all IgE and eosinophil ranges (odds ratio >1), except tioR 2.5mg at the very lowest IgE and eosinophil values (MezzoTinA-asthmaÒ). CONCLUSIONS: Once-daily tiotropium RespimatÒ add-on to at least ICS improved asthma symptom control in patients with moderate or severe symptomatic asthma, across the range of IgE and eosinophil values, supporting findings from conventional subgroup analyses.
685
Feasibility of Using Treatment Response Thresholds for Lung Function and Asthma Symptom Variables As Indicators of Asthma Control in Patients with Moderate to Severe Asthma
David J. Slade1, Michael DePietro1, John Horton1, Donald P. Tashkin2, Bradley E. Chipps, MD3; 1AstraZeneca LP, Wilmington, DE, 2University of California, Los Angeles, CA, 3Capital Allergy & Respiratory Disease Center, Sacramento, CA. RATIONALE: Simple tools are needed in clinical practice for monitoring asthma control. METHODS: This post hoc analysis (12-week study; NCT00652002) in moderate-to-severe asthma patients assessed the relationship between loss of asthma control (defined as withdrawal due to predefined asthma event during the treatment period) and response thresholds for lung function and symptoms. Response thresholds were based on mean changes from _100-mL improvement in forced baseline during treatment period: > _30-L/min improvement in evening expiratory volume in 1 second (FEV1), > _0.5-point decrease in asthma symptom peak expiratory flow (PEF), and > score (4-point scale). Data were evaluated overall and by treatment (twice-daily budesonide [BUD]/formoterol [FM] pMDI 320/9mg [n5107], BUD pMDI 320mg [n593], FM DPI 9mg [n598], or placebo [n591]). RESULTS: Overall, loss of asthma control was considerably more likely among non-responders (threshold not achieved) versus responders (threshold achieved) based on FEV1 (32.7% [n572/220] vs 11.8% [20/ 169]), evening PEF (29.6% [89/301] vs 3.4% [3/87]), and asthma symptom score (27.9% [88/315] vs 5.4% [4/74]). These findings were consistent across treatments; however, loss of asthma control was less common with BUD/FM (nonresponders vs responders: FEV1 [15.4% vs 4.4%], PEF [14.0% vs 2.0%], symptoms [11.7% vs 0.0%]) and BUD (FEV1 [21.6% vs 11.9%]; PEF [19.4% vs 6.3%]; symptoms [18.2% vs 12.5%]) versus FM (FEV1 [43.3% vs 18.4%]; PEF [38.6% vs 6.7%]; symptoms [41.0% vs 5.0%] and placebo (FEV1 [41.4% vs 23.8%]; PEF [40.5% vs 0%]; symptoms [39.8% vs 12.5%]). CONCLUSIONS: Findings confirm the feasibility of using specific response thresholds in monitoring asthma control during initiation of treatment. Supported by AstraZeneca, LP.