{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:50Z","timestamp":1790402510931,"version":"4.1.0"},"reference-count":26,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Verona Pharma plc"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Chron Respir Dis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The efficacy and safety of ensifentrine, a novel PDE3\/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible patients had moderate to severe COPD, were aged 40\u201380\u00a0years, and were symptomatic at randomization. Patients were randomized 5:3, receiving twice-daily ensifentrine 3\u00a0mg or placebo via standard jet nebulizer over 24\u00a0weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The pooled post-hoc analysis included 485 LAMA patients and 272 LABA + ICS patients. Ensifentrine showed lung function improvement over placebo at week 12, including average FEV\n                      <jats:sub>1<\/jats:sub>\n                      AUC\n                      <jats:sub>0\u201312\u00a0h<\/jats:sub>\n                      in the LAMA (placebo-corrected least squares mean change from baseline [LSMC], 92\u00a0mL; 95% CI, 54, 131; p &lt; 0.001) and LABA + ICS subgroups (LSMC, 74\u00a0mL; 95% CI, 27, 121; p = 0.002). Ensifentrine reduced the rate and risk of exacerbations in both LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively) subgroups. Ensifentrine-treated patients reported improvement in symptoms and quality of life over 24\u00a0weeks. The safety profile of ensifentrine in each subgroup was similar to the profile in the pooled modified intention-to-treat population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nebulized ensifentrine offers a novel non-steroidal anti-inflammatory and bronchodilator treatment added to existing LAMA or LABA + ICS treatment options in patients with moderate to severe, symptomatic COPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/14799731251314874","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T11:44:04Z","timestamp":1737805444000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1\/2 studies"],"prefix":"10.1177","volume":"22","author":[{"given":"Mark","family":"Dransfield","sequence":"first","affiliation":[{"name":"Medicine\/Pulmonary, Allergy and Critical Care, University of Alabama at Birmingham and the Birmingham VA Medical Center, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Kalhan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Reyner","sequence":"additional","affiliation":[{"name":"Verona Pharma plc, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L","family":"Dixon","sequence":"additional","affiliation":[{"name":"Verona Pharma plc, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Rheault","sequence":"additional","affiliation":[{"name":"Verona Pharma plc, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen Ann","family":"Rickard","sequence":"additional","affiliation":[{"name":"Verona Pharma plc, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-588X","authenticated-orcid":false,"given":"Antonio","family":"Anzueto","sequence":"additional","affiliation":[{"name":"South Texas Veterans Health Care System, University of Texas Health, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"bibr1-14799731251314874","unstructured":"Global health estimates. 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