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Jadwiga A. Wedzicha - One of the best experts on this subject based on the ideXlab platform.
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effect of erdosteine on copd Exacerbations in copd patients with moderate airflow limitation
International Journal of Chronic Obstructive Pulmonary Disease, 2019Co-Authors: Peter M A Calverley, Roberto Dal W Negro, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Mario Cazzola, Jadwiga A. WedzichaAbstract:Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of Exacerbations in moderate and severe COPD with a history of Exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear. Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined Exacerbation rate and duration, time to first Exacerbation, and Exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U-tests, or log rank tests. Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 Exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an Exacerbation. There was a 47% reduction in the mean Exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 Exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild Exacerbation rate (0.23 vs 0.53 mild Exacerbations per-patient per-year, P=0.001). Mean duration of Exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe Exacerbations. Mean time to first Exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean Exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001). Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, Exacerbations in patients with moderate COPD and a history of Exacerbations.
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S102 Eosinophil counts as a predictor of future COPD Exacerbations in the DYNAGITO trial
COPD: inflammation smoking and exacerbations, 2019Co-Authors: Peter M A Calverley, Jadwiga A. Wedzicha, Christine Jenkins, A. De La Hoz, Florian Voß, K. F. Rabe, Antonio AnzuetoAbstract:Background There is conflicting evidence from previous studies as to whether eosinophil counts predict the risk of future Exacerbations in COPD. Aims In this post hoc analysis, we investigated the link between baseline eosinophil count and moderate/severe Exacerbation rates during the DYNAGITO trial. Methods DYNAGITO was a 52-week, double-blind, randomised trial in patients with COPD with FEV1 Results At baseline, 81% of patients had an eosinophil count ≤300 cells/µL and 49% had an eosinophil count ≤150 cells/µL. 65–76% of patients were receiving ICS across eosinophil subgroups. Similar rates of moderate/severe Exacerbations were observed across eosinophil subgroups (figure). Rates were similar across eosinophil counts in patient subgroups with low or high Exacerbation history. Conclusions Relatively few patients had an eosinophil count >300 cells/µL, and there was no increase in Exacerbation rates with increasing baseline eosinophil count in the total population, or in patients with low or high Exacerbation history. In this population, many of whom were receiving ICS, Exacerbation history, but not blood eosinophil count, was an important determinant of Exacerbation risk.
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Eosinophil counts as a predictor of future COPD Exacerbations in the DYNAGITO trial
Monitoring airway disease, 2019Co-Authors: Peter M A Calverley, Jadwiga A. Wedzicha, Klaus F Rabe, Christine Jenkins, A. De La Hoz, Florian Voß, Antonio AnzuetoAbstract:Background: There is conflicting evidence from previous studies as to whether eosinophil counts predict the risk of future Exacerbations in COPD. Aims: In this post hoc analysis, we investigated the link between baseline eosinophil count and moderate/severe Exacerbation rates during the DYNAGITO trial. Methods: DYNAGITO was a 52-week, double-blind, randomised trial in patients with COPD with FEV1 Results: At baseline, 81% of patients had an eosinophil count ≤300 cells/µL and 49% had an eosinophil count ≤150 cells/µL. 65–76% of patients were receiving ICS across eosinophil subgroups. Similar rates of moderate/severe Exacerbations were observed across eosinophil subgroups (Figure). Rates were similar across eosinophil counts in patient subgroups with low or high Exacerbation history. Conclusions: Relatively few patients had an eosinophil count >300 cells/µL, and there was no increase in Exacerbation rates with increasing baseline eosinophil count in the total population, or in patients with low or high Exacerbation history. In this population, many of whom were receiving ICS, Exacerbation history, but not blood eosinophil count, was an important determinant of Exacerbation risk.
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effect of erdosteine in moderately severe copd patients
European Respiratory Journal, 2018Co-Authors: Peter M A Calverley, Roberto Dal W Negro, Martin Iversen, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Jadwiga A. WedzichaAbstract:Background: In RESTORE study (528 pts, GOLD II-III) erdosteine 300 mg bid added to usual COPD therapy reduced Exacerbation rate by 17.1% (p=0.01) and lowered duration by 24.6% (p=0.02). Aim and Objective: To assess the effect of erdosteine on Exacerbation rate and time to first Exacerbation in moderately severe COPD spirometrically defined patients. Methods: Exacerbations were defined as a symptomatic worsening requiring change in regular medication or health care resources utilization. In this post-hoc analysis we consider 254 GOLD II (2011 definition) patients. The frequency of Exacerbations per patient/year (12 months treatment) were analyzed non-parametrically (Wilcoxon rank sum test), the time free from first Exacerbation using the log-rank test (Kaplan–Meier). Results: Compared to more severe patients, GOLD II patients had similar baseline characteristics but higher FEV1 and FVC values. After 1-year treatment in GOLD II subgroup, 74 Exacerbations (57.8%) have been registered in the placebo vs. 53 (42.1%) in the erdosteine group. Erdosteine reduced the Exacerbation rate by 47% (OR: 0.530, 95% CI 0.322-0.872, p= 0.017). This result was independent from individual variables or background treatment including ICS use. Additionally erdosteine increased the time to first Exacerbation (Median time: 183 vs. 167 days Δ% +7.1 vs placebo P>0.001). Conclusions: Erdosteine significantly reduced the Exacerbation rate and increase the time to first Exacerbation. Although the time to first event was a less sensitive marker in the total study population it improved significantly in this subgroup with a large benefit on Exacerbation rate, suggesting a potential role of erdosteine in moderately severe COPD.
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effect of erdosteine on the rate and duration of copd Exacerbations the restore study
European Respiratory Journal, 2017Co-Authors: Roberto Dal W Negro, Martin Iversen, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Jadwiga A. Wedzicha, Peter M A CalverleyAbstract:Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) Exacerbations and antioxidants can decrease Exacerbation rates, although we lack data about the effect of such drugs on Exacerbation duration. The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40–80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute Exacerbations during the study. In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the Exacerbation rate by 19.4% (0.91 versus . 1.13 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild Exacerbations was 57.1% (0.23 versus 0.54 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe Exacerbations (0.68 versus 0.59 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the Exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p In patients with COPD, erdosteine can reduce both the rate and duration of Exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.
Peter M A Calverley - One of the best experts on this subject based on the ideXlab platform.
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effect of erdosteine on copd Exacerbations in copd patients with moderate airflow limitation
International Journal of Chronic Obstructive Pulmonary Disease, 2019Co-Authors: Peter M A Calverley, Roberto Dal W Negro, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Mario Cazzola, Jadwiga A. WedzichaAbstract:Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of Exacerbations in moderate and severe COPD with a history of Exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear. Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined Exacerbation rate and duration, time to first Exacerbation, and Exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U-tests, or log rank tests. Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 Exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an Exacerbation. There was a 47% reduction in the mean Exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 Exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild Exacerbation rate (0.23 vs 0.53 mild Exacerbations per-patient per-year, P=0.001). Mean duration of Exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe Exacerbations. Mean time to first Exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean Exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001). Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, Exacerbations in patients with moderate COPD and a history of Exacerbations.
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S102 Eosinophil counts as a predictor of future COPD Exacerbations in the DYNAGITO trial
COPD: inflammation smoking and exacerbations, 2019Co-Authors: Peter M A Calverley, Jadwiga A. Wedzicha, Christine Jenkins, A. De La Hoz, Florian Voß, K. F. Rabe, Antonio AnzuetoAbstract:Background There is conflicting evidence from previous studies as to whether eosinophil counts predict the risk of future Exacerbations in COPD. Aims In this post hoc analysis, we investigated the link between baseline eosinophil count and moderate/severe Exacerbation rates during the DYNAGITO trial. Methods DYNAGITO was a 52-week, double-blind, randomised trial in patients with COPD with FEV1 Results At baseline, 81% of patients had an eosinophil count ≤300 cells/µL and 49% had an eosinophil count ≤150 cells/µL. 65–76% of patients were receiving ICS across eosinophil subgroups. Similar rates of moderate/severe Exacerbations were observed across eosinophil subgroups (figure). Rates were similar across eosinophil counts in patient subgroups with low or high Exacerbation history. Conclusions Relatively few patients had an eosinophil count >300 cells/µL, and there was no increase in Exacerbation rates with increasing baseline eosinophil count in the total population, or in patients with low or high Exacerbation history. In this population, many of whom were receiving ICS, Exacerbation history, but not blood eosinophil count, was an important determinant of Exacerbation risk.
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Eosinophil counts as a predictor of future COPD Exacerbations in the DYNAGITO trial
Monitoring airway disease, 2019Co-Authors: Peter M A Calverley, Jadwiga A. Wedzicha, Klaus F Rabe, Christine Jenkins, A. De La Hoz, Florian Voß, Antonio AnzuetoAbstract:Background: There is conflicting evidence from previous studies as to whether eosinophil counts predict the risk of future Exacerbations in COPD. Aims: In this post hoc analysis, we investigated the link between baseline eosinophil count and moderate/severe Exacerbation rates during the DYNAGITO trial. Methods: DYNAGITO was a 52-week, double-blind, randomised trial in patients with COPD with FEV1 Results: At baseline, 81% of patients had an eosinophil count ≤300 cells/µL and 49% had an eosinophil count ≤150 cells/µL. 65–76% of patients were receiving ICS across eosinophil subgroups. Similar rates of moderate/severe Exacerbations were observed across eosinophil subgroups (Figure). Rates were similar across eosinophil counts in patient subgroups with low or high Exacerbation history. Conclusions: Relatively few patients had an eosinophil count >300 cells/µL, and there was no increase in Exacerbation rates with increasing baseline eosinophil count in the total population, or in patients with low or high Exacerbation history. In this population, many of whom were receiving ICS, Exacerbation history, but not blood eosinophil count, was an important determinant of Exacerbation risk.
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effect of erdosteine in moderately severe copd patients
European Respiratory Journal, 2018Co-Authors: Peter M A Calverley, Roberto Dal W Negro, Martin Iversen, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Jadwiga A. WedzichaAbstract:Background: In RESTORE study (528 pts, GOLD II-III) erdosteine 300 mg bid added to usual COPD therapy reduced Exacerbation rate by 17.1% (p=0.01) and lowered duration by 24.6% (p=0.02). Aim and Objective: To assess the effect of erdosteine on Exacerbation rate and time to first Exacerbation in moderately severe COPD spirometrically defined patients. Methods: Exacerbations were defined as a symptomatic worsening requiring change in regular medication or health care resources utilization. In this post-hoc analysis we consider 254 GOLD II (2011 definition) patients. The frequency of Exacerbations per patient/year (12 months treatment) were analyzed non-parametrically (Wilcoxon rank sum test), the time free from first Exacerbation using the log-rank test (Kaplan–Meier). Results: Compared to more severe patients, GOLD II patients had similar baseline characteristics but higher FEV1 and FVC values. After 1-year treatment in GOLD II subgroup, 74 Exacerbations (57.8%) have been registered in the placebo vs. 53 (42.1%) in the erdosteine group. Erdosteine reduced the Exacerbation rate by 47% (OR: 0.530, 95% CI 0.322-0.872, p= 0.017). This result was independent from individual variables or background treatment including ICS use. Additionally erdosteine increased the time to first Exacerbation (Median time: 183 vs. 167 days Δ% +7.1 vs placebo P>0.001). Conclusions: Erdosteine significantly reduced the Exacerbation rate and increase the time to first Exacerbation. Although the time to first event was a less sensitive marker in the total study population it improved significantly in this subgroup with a large benefit on Exacerbation rate, suggesting a potential role of erdosteine in moderately severe COPD.
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effect of erdosteine on the rate and duration of copd Exacerbations the restore study
European Respiratory Journal, 2017Co-Authors: Roberto Dal W Negro, Martin Iversen, Giovanni A Fontana, Arrigo F G Cicero, Edoardo Pozzi, Clive P Page, Jadwiga A. Wedzicha, Peter M A CalverleyAbstract:Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) Exacerbations and antioxidants can decrease Exacerbation rates, although we lack data about the effect of such drugs on Exacerbation duration. The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40–80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute Exacerbations during the study. In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the Exacerbation rate by 19.4% (0.91 versus . 1.13 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild Exacerbations was 57.1% (0.23 versus 0.54 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe Exacerbations (0.68 versus 0.59 Exacerbations·patient −1 ·year −1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the Exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p In patients with COPD, erdosteine can reduce both the rate and duration of Exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.
Donald Banerji - One of the best experts on this subject based on the ideXlab platform.
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late breaking abstract indacaterol glycopyrronium ind gly reduces the risk of Exacerbations versus salmeterol fluticasone sfc in moderate to very severe copd patients irrespective of prior ics laba lama therapy the flame study
European Respiratory Journal, 2016Co-Authors: Jadwiga A. Wedzicha, Karen Mezzi, Tim Ayers, Francesco Patalano, Chau Thach, Robert Fogel, Donald BanerjiAbstract:Introduction FLAME was the first study to show superiority of IND/GLY (LABA/LAMA) in reducing risk of Exacerbations vs. SFC (LABA/ICS) in COPD patients (pts) with history of Exacerbations. We report results regarding effect of IND/GLY vs. SFC on COPD Exacerbations in pts with or without prior ICS/LABA/LAMA triple therapy. Methods FLAME, a 52-week, randomised, double-blind study, compared once-daily IND/GLY 110/50µg vs. twice-daily SFC 50/500μg in pts with moderate-to-very severe COPD with ≥1 Exacerbation in previous year. In this post-hoc analysis, time to first COPD Exacerbation (mild, moderate or severe) and moderate/severe COPD Exacerbation with IND/GLY vs. SFC were analysed. Additionally, treatment effects on rates of Exacerbations were assessed in these pts. Results Of 3354 pts included in this analysis, 1148 (34.2%) were on prior triple therapy. IND/GLY significantly reduced the risk of any Exacerbation and moderate/severe Exacerbation vs. SFC in pts, irrespective of prior triple therapy (table). IND/GLY numerically reduced the rate of any and moderate/severe COPD Exacerbations vs. SFC in pts with/without prior triple therapy (table). Conclusion IND/GLY significantly reduces risk of Exacerbations versus SFC, irrespective of prior triple therapy in exacerbating patients with moderate-to-very severe COPD.
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indacaterol glycopyrronium ind gly reduces Exacerbations compared with salmeterol fluticasone sfc in various sub groups from the flame study
European Respiratory Journal, 2016Co-Authors: Jadwiga A. Wedzicha, Tim Ayers, Francesco Patalano, Chau Thach, Robert Fogel, Kenneth R Chapman, Angel Fowlertaylor, Petter Olsson, Donald BanerjiAbstract:Introduction LABA/ICS combination and/or LAMA have been the first choice of treatment for COPD patients with high risk of Exacerbation. FLAME is the first study which compared rate and risk of Exacerbations with IND/GLY to SFC in patients with at least one Exacerbation in the previous year. Methods Patients with post-bronchodilator FEV 1 ≥25%- Results In total, 3362 patients were randomised. The rate of all Exacerbations was lower with IND/GLY compared with SFC (Figure 1A) in subgroups defined by age, smoking status, Exacerbation history, and disease severity. IND/GLY also reduced rate of moderate or severe Exacerbations in all subgroups except for <55 years age and GOLD 4, however; the patient number in these subgroups were small (Figure 1B). Similar results were observed for all and moderate or severe Exacerbations for other subgroups. Conclusions IND/GLY significantly reduced all and moderate or severe Exacerbations, compared with SFC in many subgroups, demonstrating a consistent trend to the overall population.
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qva149 compared with salmeterol fluticasone sfc on Exacerbations and its correlation with baseline blood eosinophils a pooled analysis of lantern and illuminate
European Respiratory Journal, 2015Co-Authors: Jadwiga A. Wedzicha, Karen Mezzi, Robert Fogel, D Price, Donald BanerjiAbstract:Introduction: This pooled analysis compared the incidence of moderate or severe COPD Exacerbations with QVA149 vs SFC. We also investigated if baseline blood eosinophil (EOS) count was a predictor of Exacerbation risk, and magnitude of treatment effect on this risk. Methods: All patients (pts) from two 26-week double-blind studies were included in this analysis. 1263 moderate-to-severe COPD pts with ≤1 Exacerbation in the previous year were randomised (1:1) to QVA149 or SFC. Results: In the overall pool, the rate of moderate or severe Exacerbations was significantly lower with QVA149 vs SFC (RR [95% CI]: 0.67 [0.48-0.94]; p=0.021). There was a trend (p=0.08) towards increased Exacerbation rate with increased baseline blood EOS count. In pts with baseline blood EOS count of 3 and 150-300/mm 3 , QVA149 showed 45% and 43% reduction in the risk of Exacerbations, respectively compared to SFC (Figure 1). In pts with >300/mm 3 blood EOS at baseline (12% of study population), risk of Exacerbations was lower with SFC. Conclusion: QVA 149 was more effective in reducing Exacerbation risk in pts with baseline blood eosinophil 3 (88% of pool) and SFC in pts with >300/mm 3 (12% of pool). These data suggest that baseline blood eosinophil count may be a useful biomarker in assessing potential benefit of QVA149 over SFC in reducing Exacerbations in COPD patients.
Michiaki Mishima - One of the best experts on this subject based on the ideXlab platform.
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Tiotropium/olodaterol versus tiotropium in Japanese patients with COPD: results from the DYNAGITO study.
International Journal of Chronic Obstructive Pulmonary Disease, 2018Co-Authors: Masakazu Ichinose, Masaharu Nishimura, Manabu Akimoto, Yasuhiro Kurotori, Yihua Zhao, Michiaki MishimaAbstract:Background: The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe Exacerbations of COPD. This is a prespecified analysis of the DYNAGITO data in Japanese patients. Patients and methods: Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe Exacerbation in the previous 12 months. Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese. The primary endpoint was the annualized rate of moderate-to-severe COPD Exacerbations. The key secondary endpoint was the time to first moderate-to-severe COPD Exacerbation, and other secondary endpoints included the annualized rate of Exacerbations leading to hospitalization, time to first COPD Exacerbation leading to hospitalization, and all-cause mortality. Safety data were analyzed descriptively. Results: Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD Exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434). The risk of a first moderate-to-severe COPD Exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant. The annualized rate of COPD Exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654). The adverse event incidence was balanced between treatment arms. Conclusion: In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing Exacerbations. Both treatments were well tolerated.
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tiotropium olodaterol versus tiotropium in japanese patients with copd results from the dynagito study
International Journal of Chronic Obstructive Pulmonary Disease, 2018Co-Authors: Masakazu Ichinose, Masaharu Nishimura, Manabu Akimoto, Yasuhiro Kurotori, Yihua Zhao, Michiaki MishimaAbstract:Background: The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe Exacerbations of COPD. This is a prespecified analysis of the DYNAGITO data in Japanese patients. Patients and methods: Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe Exacerbation in the previous 12 months. Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese. The primary endpoint was the annualized rate of moderate-to-severe COPD Exacerbations. The key secondary endpoint was the time to first moderate-to-severe COPD Exacerbation, and other secondary endpoints included the annualized rate of Exacerbations leading to hospitalization, time to first COPD Exacerbation leading to hospitalization, and all-cause mortality. Safety data were analyzed descriptively. Results: Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD Exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434). The risk of a first moderate-to-severe COPD Exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant. The annualized rate of COPD Exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654). The adverse event incidence was balanced between treatment arms. Conclusion: In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing Exacerbations. Both treatments were well tolerated.
R Buhl - One of the best experts on this subject based on the ideXlab platform.
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p296 effect of tiotropium olodaterol therapy on copd Exacerbations in the tonado studies
Thorax, 2016Co-Authors: Eric Derom, Fle M Zcaron, L Gronke, R BuhlAbstract:Rationale The lung-function efficacy, symptomatic benefits and safety of combined tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD, was established in the year-long TONADO ® studies (NCT01431274; NCT01431287). It is unknown if these benefits of T/O translate into a reduction in COPD Exacerbation rate. Methods Two replicate, randomised, double-blind, parallel-group trials assessed T/O 2.5/5 μg and T/O 5/5 μg compared to the monocomponents T 5 μg, T 2.5 μg and O 5 µg (all delivered via Respimat ® inhaler) in patients with moderate to very severe COPD. Primary end points included lung function (forced expiratory volume in 1 second [FEV 1 ] area under the curve from 0–3 hours response, trough FEV 1 response) and quality of life (SGRQ). Analysis of the number of Exacerbations and time to Exacerbation was pre-specified using data from the combined TONADO ® studies. We present data from the T/O and T treatment arms. Results 4124 patients were evaluable for the T/O and T treatment arms. Moderate or severe Exacerbations occurred in 27.7% of patients with T/O 5/5 μg, 25.8% of patients with T/O 2.5/5 μg, 28.8% with T 5 μg and 29.6% with T 2.5 μg. Severe Exacerbations occurred in 5.9% of patients receiving T/O 5/5 μg, 4.5% receiving T/O 2.5/5 μg, 4.5% receiving T 5 μg and 5.2% receiving T 2.5 μg. The treatment comparisons for any Exacerbation and moderate/severe Exacerbations were generally consistent between the two studies, except for a higher number of severe Exacerbations with T/O 5/5 μg in TONADO ® 1 only (Table). Conclusions Although there were fewer Exacerbations overall with T/O 2.5/5 µg or 5/5 µg compared to T 2.5 µg or 5 µg, and a numerically longer time to first moderate/severe Exacerbation, the TONADO ® studies did not show a significant difference in the hazard ratios for time to Exacerbation end points. These findings are partially attributable to a higher number of severe Exacerbations with T/O 5/5 µg in TONADO ® 1. TONADO ® was not designed for formal comparison of Exacerbations with T/O versus T; however, a study powered to assess this is ongoing. Funding Boehringer Ingelheim. Please refer to page A273 for declarations of interest in relation to abstract P296.
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P296 Effect of tiotropium/olodaterol therapy on copd Exacerbations in the tonado® studies
Thorax, 2016Co-Authors: Eric Derom, Florian Voß, L Gronke, M Fle Zcaron, R BuhlAbstract:Rationale The lung-function efficacy, symptomatic benefits and safety of combined tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD, was established in the year-long TONADO ® studies (NCT01431274; NCT01431287). It is unknown if these benefits of T/O translate into a reduction in COPD Exacerbation rate. Methods Two replicate, randomised, double-blind, parallel-group trials assessed T/O 2.5/5 μg and T/O 5/5 μg compared to the monocomponents T 5 μg, T 2.5 μg and O 5 µg (all delivered via Respimat ® inhaler) in patients with moderate to very severe COPD. Primary end points included lung function (forced expiratory volume in 1 second [FEV 1 ] area under the curve from 0–3 hours response, trough FEV 1 response) and quality of life (SGRQ). Analysis of the number of Exacerbations and time to Exacerbation was pre-specified using data from the combined TONADO ® studies. We present data from the T/O and T treatment arms. Results 4124 patients were evaluable for the T/O and T treatment arms. Moderate or severe Exacerbations occurred in 27.7% of patients with T/O 5/5 μg, 25.8% of patients with T/O 2.5/5 μg, 28.8% with T 5 μg and 29.6% with T 2.5 μg. Severe Exacerbations occurred in 5.9% of patients receiving T/O 5/5 μg, 4.5% receiving T/O 2.5/5 μg, 4.5% receiving T 5 μg and 5.2% receiving T 2.5 μg. The treatment comparisons for any Exacerbation and moderate/severe Exacerbations were generally consistent between the two studies, except for a higher number of severe Exacerbations with T/O 5/5 μg in TONADO ® 1 only (Table). Conclusions Although there were fewer Exacerbations overall with T/O 2.5/5 µg or 5/5 µg compared to T 2.5 µg or 5 µg, and a numerically longer time to first moderate/severe Exacerbation, the TONADO ® studies did not show a significant difference in the hazard ratios for time to Exacerbation end points. These findings are partially attributable to a higher number of severe Exacerbations with T/O 5/5 µg in TONADO ® 1. TONADO ® was not designed for formal comparison of Exacerbations with T/O versus T; however, a study powered to assess this is ongoing. Funding Boehringer Ingelheim. Please refer to page A273 for declarations of interest in relation to abstract P296.
