scholarly journals Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis

2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  

Abstract Background : Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV 1 ) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV 1 , St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included ​ patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV 1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% and ≥200 mL increase in FEV 1 ) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV 1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV 1 versus placebo in the ITT population and all subgroups. There were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Revefenacin could be a therapeutic option among patients with markers of more severe COPD.

2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  

Abstract Background: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV 1 ) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials (revefenacin 175 µg [n = 395] and placebo [n = 417]) was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV 1 , St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. We included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV 1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% in FEV 1 ) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV 1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. There was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV 1 versus placebo in the ITT population and all subgroups. There were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Revefenacin could be a therapeutic option among patients with markers of more severe COPD.


2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  

Abstract Background: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% and ≥200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.


2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  

Abstract Background: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% and ≥200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years.Conclusions: Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.Trial registration: Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; 22 May 2015] and 0127 [NCT02512510; 28 July 2015]).


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kenneth R. Chapman ◽  
Robert A. Wise ◽  
Benjamin M. Scirica ◽  
Deepak L. Bhatt ◽  
Sami Z. Daoud ◽  
...  

Abstract Background Beta-blocker therapies for cardiovascular comorbidities are often withheld in patients with chronic obstructive pulmonary disease (COPD) due to potential adverse effects on airway obstruction. We carried out a post hoc analysis to determine the efficacy and safety of aclidinium in patients with moderate-to-very severe COPD and increased cardiovascular risk receiving beta-blockers at baseline versus non-users. Methods ASCENT-COPD was a Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients were randomized 1:1 to aclidinium or placebo twice-daily for up to 3 years. Outcomes included risk of (time to first) major adverse cardiovascular events (MACE), all-cause mortality, and lung function over 3 years, and exacerbations over 1 year. Results Of 3589 patients, 1269 (35.4%) used beta-blockers and 2320 (64.6%) were non-users at baseline. Aclidinium did not statistically increase the risk of MACE (beta-blocker user: hazard ratio 1.01 [95% CI 0.62–1.64]; non-user: 0.80 [0.51–1.24]; interaction P = 0.48) or all-cause mortality (beta-blocker user: 1.13 [0.78–1.64]; non-user: 0.89 [0.62–1.26]; interaction P = 0.35), in patients using beta-blockers. Aclidinium reduced annualized rate of moderate-to-severe COPD exacerbation (beta-blocker user: rate ratio 0.75 [95% CI 0.60–0.94, P = 0.013]; non-user: 0.79 [0.67–0.93, P = 0.005]), delayed time to first exacerbation, and improved lung function versus placebo. There was greater trough FEV1 benefit in beta-blocker users versus non-users (least squares mean difference at 52 weeks: 111 mL [95% CI 74 mL–147 mL] versus 69 mL [42 mL–97 mL]; interaction P = 0.041). Conclusions This post hoc analysis supports long-acting anti-muscarinic use with concomitant beta-blockers in patients with moderate-to-very severe COPD and cardiovascular comorbidity. Trial registration: ClinicalTrials.gov, NCT01966107, Registered 16 October 2013, https://clinicaltrials.gov/ct2/show/NCT01966107.


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