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Safety of Bronchial Thermoplasty in High Risk Patients with Severe Asthma
AB10 Abstracts
SATURDAY
31
Patient-Reported Outcomes and Quality of Improved with Fluticasone Propionate Fluticasone Propionate/Salmeterol Multidose Powder Inhalers Versus Placebo in Patients Persistent Asthma
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
Life and Dry with
Gordon Raphael, MD1, Gloria Yiu, MS2, Anat Sakov, PhD3, Siyu Liu, MD, PhD2, and Cynthia Caracta, MD, FCCP2; 1Bethesda Allergy, Asthma and Research Center, Bethesda, MD, 2Teva Pharmaceuticals, Frazer, PA, 3Teva Pharmaceuticals, Netanya, Israel. RATIONALE: Patient-reported outcomes, including quality of life, were evaluated in patients receiving fluticasone propionate (Fp) and fluticasone propionate/salmeterol (FS) via a novel multidose dry powder inhaler (MDPI). METHODS: This phase 3, double-blind, parallel-group study (FSS-AS_12 years) using 301; NCT02139644) evaluated asthmatic patients (ages > inhaled corticosteroids (ICS) or ICS/long-acting beta2-agonists. After a 14to 21-day run-in during which patients received albuterol metered-dose inhaler for rescue, beclomethasone dipropionate metered-dose inhaler, 40 mcg twice daily (BID), and placebo MDPI BID, patients randomly received Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo BID for 12 weeks. Efficacy and safety outcomes were previously reported. Patient-reported outcomes including asthma symptoms, rescue medication use, Asthma Quality of Life _18 years), and adverse events Questionnaire (AQLQ) scores (patients > are reported. RESULTS: The full analysis and safety populations included 640 and 641 patients, respectively. All active treatments significantly improved asthma symptom scores (p<0.05) and significantly decreased rescue medication use (p<0.05) versus placebo over 12 weeks. Improvements in AQLQ from baseline to endpoint for active treatment groups were significantly greater versus placebo (p<0.05). AQLQ improvements from baseline _0.5) for all active treatment achieved the minimal important difference (> groups. Comparisons between Fp MDPI and FS MDPI were not significant for any assessed outcome except AQLQ for Fp MDPI 100 mcg versus FS MDPI 100/12.5 mcg (p<0.05). Adverse events were similar across groups. CONCLUSIONS: Low- and mid-dose Fp MDPI and FS MDPI significantly improved patient-reported outcomes and quality of life versus placebo. Funding: Teva Pharmaceuticals.
32
Benralizumab Reduces Exacerbations in Japanese Patients with Severe, Uncontrolled Asthma: Subgroup Analysis of the Calima Trial
J Mark FitzGerald1, Ken Ohta2, Mitsuru Adachi3, Yuji Tohda4, Tadashi Kamei5, Motokazu Kato6, Masayuki Takanuma7, Tadahiro Kakuno7, Nobuyuki Imai7, Yanping Wu8, Magnus Aurivillius9, and Mitchell Goldman8; 1Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, Canada, 2National Hospital Organization Tokyo National Hospital, Tokyo, Japan, 3International University of Health and Welfare Sanno Hospital, Tokyo, Japan, 4Kindai University Faculty of Medicine, Osaka, Japan, 5Kamei Respiratory Clinic, Takamatsu, Japan, 6 Kishiwada City Hospital, Osaka, Japan, 7Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan, 8AstraZeneca, Gaithersburg, MD, 9AstraZeneca, M€ olndal, Sweden. RATIONALE: In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, improved lung function, and alleviated symptoms for patients with severe, uncontrolled, eosinophilic asthma. This subanalysis evaluated benralizumab’s efficacy and safety for Japanese patients who participated in CALIMA. METHODS: CALIMA (NCT01914757) was a randomized controlled trial of 1,306 patients (aged 12–75 years) with severe asthma uncontrolled by medium- to high-dosage inhaled corticosteroids (ICS) and long-acting b2-agonists. Patients received 56 weeks benralizumab 30 mg SC either every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W), or
placebo SC Q4W. Primary analysis population was 728 patients receiving _300 cells/mL. This subhigh-dosage ICS with baseline blood eosinophils > analysis covered Japanese patients from this group. RESULTS: Of 83 patients randomized in Japan, 46 were receiving high_300 cells/mL. dosage ICS and had baseline blood eosinophils > Benralizumab reduced the annual rate of asthma exacerbations by 66% (Q4W; rate 0.83, rate ratio 0.34 [95% CI 0.11–0.99], n515) and 83% (Q8W; rate 0.42, rate ratio 0.17 [0.05–0.60], n515), vs. placebo (rate 2.45, n516); increased pre-bronchodilator FEV1by 0.334 L (Q4W; 95% CI 0.020–0.647) and 0.198 L (Q8W; 95% CI –0.118 to 0.514), vs. placebo; and decreased total asthma symptom score by –0.17 (Q4W; 95% CI (–0.82 to 0.48) and –0.24 (Q8W; 95% CI –0.87 to 0.40), vs. placebo. Incidence of adverse events was consistent with the overall CALIMA group. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased FEV1, decreased symptoms, and was generally well-tolerated for Japanese patients with severe, uncontrolled, eosinophilic asthma.
33
Safety of Bronchial Thermoplasty in High Risk Patients with Severe Asthma
Rana Kanaan1, Charlie Strange1, Douglas Kyle Hogarth2, Walter Mark Boomer3, Lisa M. Kopas, MD4, Shanaya Suchak5, Michelle Cornacchia6, Julia Behrend2, Nicholas J. Pastis1, and John B. Cox, MD1; 1Pulmonary,Critical Care, Allergy and Sleep division, Medical University of South Carolina, Charleston, SC, 2University of Chicago, Chicago, 3Pulmonary Medicine Associates, Tulsa, OK, 4Pulmonary Critical Care and Sleep Medicine Co, Houston, TX, 5Oklahoma State University, Tulsa, OK, 6 Baylor College of Medicine, Houston, TX. RATIONALE: The AIR2 study that established FDA approval for bronchial thermoplasty (BT) has excluded high risk asthma patients for safety concerns. Individuals excluded from the study have more disease burden, fewer effective treatment options, and more hospitalizations. METHODS: We pool and describe the consecutive case treatment experience from 4 centers for individuals who failed to meet the inclusion criteria for the AIR2 study. RESULTS: 94 consecutive patients had BT performed during general anesthesia (n551), or conscious sedation (n540). Patient characteristics _ 20 packincluded age 52.6 +13.9 (range 18-84), female sex 72%, smoker > years 20%, mean prebronchodilator FEV1 % predicted 56.9 6 18.6% (range 24-101%), baseline prednisone dose 11 6 16 mg (range 0-60), and omalizumab use (n520). AIR2 exclusions included age >65 (n518, 19%), FEV1 <60% (n549, 54%), systemic corticosteroid dose > 10 mg daily (n528, 31%), frequent exacerbations (n553, 61%), immunosuppressive therapy (n52) or life threating asthma (n528, 39%). Procedural complications occurred in 4 individuals. Two cases of hypoxemia during conscious sedation prompted abortion of the procedure. Both were rescheduled. Post-extubation bronchospasm occurred in one patient. One case of hemoptysis was seen in the week after the procedure. 15% of patients stayed for overnight observation. There were no cases of postoperative respiratory failure. Over the following 6 weeks, complications were recorded in 28% (n581). These included 21 hospitalizations for asthma in 18 individuals. In those without hospitalizations, ED visits occurred in 4 individuals, and antibiotic use in 6 individuals. CONCLUSIONS: Bronchial thermoplasty can safely be performed in high risk individuals with severe asthma.
SATURDAY
31
Patient-Reported Outcomes and Quality of Improved with Fluticasone Propionate Fluticasone Propionate/Salmeterol Multidose Powder Inhalers Versus Placebo in Patients Persistent Asthma
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
Life and Dry with
Gordon Raphael, MD1, Gloria Yiu, MS2, Anat Sakov, PhD3, Siyu Liu, MD, PhD2, and Cynthia Caracta, MD, FCCP2; 1Bethesda Allergy, Asthma and Research Center, Bethesda, MD, 2Teva Pharmaceuticals, Frazer, PA, 3Teva Pharmaceuticals, Netanya, Israel. RATIONALE: Patient-reported outcomes, including quality of life, were evaluated in patients receiving fluticasone propionate (Fp) and fluticasone propionate/salmeterol (FS) via a novel multidose dry powder inhaler (MDPI). METHODS: This phase 3, double-blind, parallel-group study (FSS-AS_12 years) using 301; NCT02139644) evaluated asthmatic patients (ages > inhaled corticosteroids (ICS) or ICS/long-acting beta2-agonists. After a 14to 21-day run-in during which patients received albuterol metered-dose inhaler for rescue, beclomethasone dipropionate metered-dose inhaler, 40 mcg twice daily (BID), and placebo MDPI BID, patients randomly received Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo BID for 12 weeks. Efficacy and safety outcomes were previously reported. Patient-reported outcomes including asthma symptoms, rescue medication use, Asthma Quality of Life _18 years), and adverse events Questionnaire (AQLQ) scores (patients > are reported. RESULTS: The full analysis and safety populations included 640 and 641 patients, respectively. All active treatments significantly improved asthma symptom scores (p<0.05) and significantly decreased rescue medication use (p<0.05) versus placebo over 12 weeks. Improvements in AQLQ from baseline to endpoint for active treatment groups were significantly greater versus placebo (p<0.05). AQLQ improvements from baseline _0.5) for all active treatment achieved the minimal important difference (> groups. Comparisons between Fp MDPI and FS MDPI were not significant for any assessed outcome except AQLQ for Fp MDPI 100 mcg versus FS MDPI 100/12.5 mcg (p<0.05). Adverse events were similar across groups. CONCLUSIONS: Low- and mid-dose Fp MDPI and FS MDPI significantly improved patient-reported outcomes and quality of life versus placebo. Funding: Teva Pharmaceuticals.
32
Benralizumab Reduces Exacerbations in Japanese Patients with Severe, Uncontrolled Asthma: Subgroup Analysis of the Calima Trial
J Mark FitzGerald1, Ken Ohta2, Mitsuru Adachi3, Yuji Tohda4, Tadashi Kamei5, Motokazu Kato6, Masayuki Takanuma7, Tadahiro Kakuno7, Nobuyuki Imai7, Yanping Wu8, Magnus Aurivillius9, and Mitchell Goldman8; 1Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, Canada, 2National Hospital Organization Tokyo National Hospital, Tokyo, Japan, 3International University of Health and Welfare Sanno Hospital, Tokyo, Japan, 4Kindai University Faculty of Medicine, Osaka, Japan, 5Kamei Respiratory Clinic, Takamatsu, Japan, 6 Kishiwada City Hospital, Osaka, Japan, 7Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan, 8AstraZeneca, Gaithersburg, MD, 9AstraZeneca, M€ olndal, Sweden. RATIONALE: In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, improved lung function, and alleviated symptoms for patients with severe, uncontrolled, eosinophilic asthma. This subanalysis evaluated benralizumab’s efficacy and safety for Japanese patients who participated in CALIMA. METHODS: CALIMA (NCT01914757) was a randomized controlled trial of 1,306 patients (aged 12–75 years) with severe asthma uncontrolled by medium- to high-dosage inhaled corticosteroids (ICS) and long-acting b2-agonists. Patients received 56 weeks benralizumab 30 mg SC either every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W), or
placebo SC Q4W. Primary analysis population was 728 patients receiving _300 cells/mL. This subhigh-dosage ICS with baseline blood eosinophils > analysis covered Japanese patients from this group. RESULTS: Of 83 patients randomized in Japan, 46 were receiving high_300 cells/mL. dosage ICS and had baseline blood eosinophils > Benralizumab reduced the annual rate of asthma exacerbations by 66% (Q4W; rate 0.83, rate ratio 0.34 [95% CI 0.11–0.99], n515) and 83% (Q8W; rate 0.42, rate ratio 0.17 [0.05–0.60], n515), vs. placebo (rate 2.45, n516); increased pre-bronchodilator FEV1by 0.334 L (Q4W; 95% CI 0.020–0.647) and 0.198 L (Q8W; 95% CI –0.118 to 0.514), vs. placebo; and decreased total asthma symptom score by –0.17 (Q4W; 95% CI (–0.82 to 0.48) and –0.24 (Q8W; 95% CI –0.87 to 0.40), vs. placebo. Incidence of adverse events was consistent with the overall CALIMA group. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased FEV1, decreased symptoms, and was generally well-tolerated for Japanese patients with severe, uncontrolled, eosinophilic asthma.
33
Safety of Bronchial Thermoplasty in High Risk Patients with Severe Asthma
Rana Kanaan1, Charlie Strange1, Douglas Kyle Hogarth2, Walter Mark Boomer3, Lisa M. Kopas, MD4, Shanaya Suchak5, Michelle Cornacchia6, Julia Behrend2, Nicholas J. Pastis1, and John B. Cox, MD1; 1Pulmonary,Critical Care, Allergy and Sleep division, Medical University of South Carolina, Charleston, SC, 2University of Chicago, Chicago, 3Pulmonary Medicine Associates, Tulsa, OK, 4Pulmonary Critical Care and Sleep Medicine Co, Houston, TX, 5Oklahoma State University, Tulsa, OK, 6 Baylor College of Medicine, Houston, TX. RATIONALE: The AIR2 study that established FDA approval for bronchial thermoplasty (BT) has excluded high risk asthma patients for safety concerns. Individuals excluded from the study have more disease burden, fewer effective treatment options, and more hospitalizations. METHODS: We pool and describe the consecutive case treatment experience from 4 centers for individuals who failed to meet the inclusion criteria for the AIR2 study. RESULTS: 94 consecutive patients had BT performed during general anesthesia (n551), or conscious sedation (n540). Patient characteristics _ 20 packincluded age 52.6 +13.9 (range 18-84), female sex 72%, smoker > years 20%, mean prebronchodilator FEV1 % predicted 56.9 6 18.6% (range 24-101%), baseline prednisone dose 11 6 16 mg (range 0-60), and omalizumab use (n520). AIR2 exclusions included age >65 (n518, 19%), FEV1 <60% (n549, 54%), systemic corticosteroid dose > 10 mg daily (n528, 31%), frequent exacerbations (n553, 61%), immunosuppressive therapy (n52) or life threating asthma (n528, 39%). Procedural complications occurred in 4 individuals. Two cases of hypoxemia during conscious sedation prompted abortion of the procedure. Both were rescheduled. Post-extubation bronchospasm occurred in one patient. One case of hemoptysis was seen in the week after the procedure. 15% of patients stayed for overnight observation. There were no cases of postoperative respiratory failure. Over the following 6 weeks, complications were recorded in 28% (n581). These included 21 hospitalizations for asthma in 18 individuals. In those without hospitalizations, ED visits occurred in 4 individuals, and antibiotic use in 6 individuals. CONCLUSIONS: Bronchial thermoplasty can safely be performed in high risk individuals with severe asthma.