Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis
Abstract Background Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated t...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12890-020-1156-4 |
| _version_ | 1818142985478471680 |
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| author | James F. Donohue Edward Kerwin Chris N. Barnes Edmund J. Moran Brett Haumann Glenn D. Crater |
| author_facet | James F. Donohue Edward Kerwin Chris N. Barnes Edmund J. Moran Brett Haumann Glenn D. Crater |
| author_sort | James F. Donohue |
| collection | DOAJ |
| description | Abstract Background Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (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 ; prospectively registered 22 May 2015] and 0127 [ NCT02512510 ; prospectively registered 28 July 2015]). |
| first_indexed | 2024-12-11T11:24:28Z |
| format | Article |
| id | doaj.art-a02dc5fee0344cab954ec9e187b55225 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-12-11T11:24:28Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-a02dc5fee0344cab954ec9e187b552252022-12-22T01:09:03ZengBMCBMC Pulmonary Medicine1471-24662020-05-0120111010.1186/s12890-020-1156-4Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysisJames F. Donohue0Edward Kerwin1Chris N. Barnes2Edmund J. Moran3Brett Haumann4Glenn D. Crater5Pulmonary Medicine, UNC School of MedicineClinical Research Institute of Southern Oregon, LLCTheravance Biopharma US, Inc.Theravance Biopharma US, Inc.Theravance Biopharma US, Inc.Theravance Biopharma US, Inc.Abstract Background Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (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 ; prospectively registered 22 May 2015] and 0127 [ NCT02512510 ; prospectively registered 28 July 2015]).http://link.springer.com/article/10.1186/s12890-020-1156-4COPDEfficacyLong-acting muscarinic antagonistNebulized therapyRevefenacin |
| spellingShingle | James F. Donohue Edward Kerwin Chris N. Barnes Edmund J. Moran Brett Haumann Glenn D. Crater Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis BMC Pulmonary Medicine COPD Efficacy Long-acting muscarinic antagonist Nebulized therapy Revefenacin |
| title | Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis |
| title_full | Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis |
| title_fullStr | Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis |
| title_full_unstemmed | Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis |
| title_short | Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis |
| title_sort | efficacy of revefenacin a long acting muscarinic antagonist for nebulized therapy in patients with markers of more severe copd a post hoc subgroup analysis |
| topic | COPD Efficacy Long-acting muscarinic antagonist Nebulized therapy Revefenacin |
| url | http://link.springer.com/article/10.1186/s12890-020-1156-4 |
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