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

• Published in: BMC pulmonary medicine 2020-05, Vol.20 (1), p.134-10, Article 134
• Main Authors: Donohue, James F, Kerwin, Edward, Barnes, Chris N, Moran, Edmund J, Haumann, Brett, Crater, Glenn D
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Administration, Inhalation; Aged; Aged, 80 and over; Benzamides - administration & dosage; Bronchodilator Agents - administration & dosage; Bronchodilators; Carbamates - administration & dosage; Cardiovascular disease; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Clinical trials; Confidence intervals; COPD; Corticosteroids; Diabetes; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Drug therapy; Dyspnea; Efficacy; FDA approval; Female; Forced Expiratory Volume; Humans; Inhalers; Long-acting muscarinic antagonist; Lung - physiopathology; Lung diseases; Male; Middle Aged; Muscarinic Antagonists - administration & dosage; Nebulized therapy; Obstructive lung disease; Patient outcomes; Patients; Population; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonology; Respiration; Revefenacin; Risk factors; Severity of Illness Index; Studies; Time Factors
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-020-1156-4

Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV ) 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. 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 , 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 30%- 75 years), and comorbidity risk factors. Revefenacin demonstrated significant improvements in FEV 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. Revefenacin showed significantly greater improvements in FEV 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. Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2