{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:48:19Z","timestamp":1787791699008,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA054268"],"award-info":[{"award-number":["R01 DA054268"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["U10\/UG1 DA013035"],"award-info":[{"award-number":["U10\/UG1 DA013035"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["K01 DA054328"],"award-info":[{"award-number":["K01 DA054328"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>It is unclear if findings from randomized controlled trials (RCT) of medications for opioid use disorder apply to real\u2010world settings. We estimated the effectiveness of buprenorphine\u2010naloxone (BUP\u2010NX) versus extended\u2010release naltrexone (XR\u2010NTX) on treatment interruption in a RCT and an observational study based on real\u2010world data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Target trial emulation to harmonize the protocol and statistical analyses of X:BOT (target trial) and the observational study (observational emulation). Baseline was randomization in the target trial and medically managed opioid withdrawal (MMOW) discharge in the observational emulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Settings<\/jats:title><jats:p>X:BOT trial and Massachusetts Public Health Data Warehouse observational data (United States).<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>The target trial included all X:BOT participants. The observational emulation trial included MMOW discharges from January 2014 to May 2016.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Treatment strategies were BUP\u2010NX versus XR\u2010NTX initiation within 28\u2009days of baseline. The outcome was treatment interruption (earliest of treatment discontinuation, incarceration, MMOW readmission, death). We estimated the 24\u2010week risk and risk difference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>In the target trial, 94% (269\/287) and 66% (187\/283) of participants randomized to BUP\u2010NX or XR\u2010NTX initiated their assigned treatment within 28\u2009days, respectively. In the observational emulation, BUP\u2010NX and XR\u2010NTX were initiated within 28\u2009days in 9% (5209\/59 076) and 3% (1813\/59 076) of MMOW discharges, respectively. The adjusted 24\u2010week treatment interruption risks (95% confidence interval) for BUP\u2010NX and XR\u2010NTX were 68% (60%,77%) and 72% (60%,83%) in the target trial [risk difference, \u22124 percentage points (pp; \u221217\u2009pp,11\u2009pp)] and 82% (81%,83%) and 93% (92%,95%) in the observational emulation [risk difference,\u201011\u2009pp (\u221213\u2009pp,\u201010\u00a0pp)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Buprenorphine\u2010naloxone might be superior to extended\u2010release naltrexone in real\u2010world settings where the majority of people struggle to remain on medications for opioid use disorder. Buprenorphine\u2010naloxone initiators had a lower risk of treatment interruption than extended\u2010release naltrexone initiators in an observational emulation, but similar risks in a randomized controlled trial, although confidence intervals were wide. Trial participation, study size and residual confounding may explain these differences.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.70040","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T08:55:30Z","timestamp":1742374530000},"page":"1634-1645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative effectiveness of extended\u2010release naltrexone versus buprenorphine\u2010naloxone on treatment interruption: Comparing findings from a reanalysis of the X:BOT RCT and harmonized target trial emulation using population\u2010based observational data"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-7830","authenticated-orcid":false,"given":"Sara","family":"Lodi","sequence":"first","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shapei","family":"Yan","sequence":"additional","affiliation":[{"name":"Section of General Internal Medicine, Department of Medicine Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bovell\u2010Ammon","sequence":"additional","affiliation":[{"name":"Section of General Internal Medicine, Department of Medicine Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-0761","authenticated-orcid":false,"given":"Paul J.","family":"Christine","sequence":"additional","affiliation":[{"name":"Section of General Internal Medicine, Department of Medicine Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather E.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Bernson","sequence":"additional","affiliation":[{"name":"Massachusetts Department of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Novo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry New York University Grossman School of Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Population Health New York University Grossman School of Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Rotrosen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry New York University Grossman School of Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Liebschutz","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Center for Research on Health Care, Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Y.","family":"Walley","sequence":"additional","affiliation":[{"name":"Section of General Internal Medicine, Department of Medicine Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R.","family":"Larochelle","sequence":"additional","affiliation":[{"name":"Section of General Internal Medicine, Department of Medicine Boston Medical Center and Boston University School of Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Provisional drug overdose death counts. 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