{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:19:54Z","timestamp":1788265194397,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pegylated\u2010interferon\u2010\u03b1 (Peg\u2010IFN\u03b1) is a treatment option for chronic hepatitis B virus (HBV) infection. To quantify treatment response variability, we conducted a model\u2010based meta\u2010analysis (MBMA) of hepatitis B surface antigen (HBsAg) loss, defined as a binary outcome based on HBsAg levels falling below the limit of detection, with Peg\u2010IFN\u03b1\u2010based regimens at end\u2010of\u2010treatment (EOT) and 24\u2009weeks post\u2010treatment. A systematic review of HBsAg loss in chronic HBV infection was performed, searching Embase, MEDLINE, and Cochrane (January 2000\u2013July 2022). Studies reporting only per\u2010protocol results were excluded; intent\u2010to\u2010treat (ITT) or modified ITT results were prioritized. Models described the proportion achieving HBsAg loss with respect to treatment regimens, exploring baseline clinical and demographic covariates. For the EOT model, 83 study\u2010strata\u2010arms (11,493 participants) were included; for the 24\u2010week model, 58 study\u2010strata\u2010arms (4267 participants) were included. In both models, Peg\u2010IFN\u03b1 duration and baseline HBsAg significantly predicted HBsAg loss (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001); baseline hepatitis B e\u2010antigen (HBeAg) was an additional predictor at EOT (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007). These covariates reduced between\u2010trial variance by 58.1% (EOT) and 77.6% (24\u2010week), highlighting their role in explaining heterogeneity. This MBMA supports clinical trial design by simulating outcomes with Peg\u2010IFN\u03b1 across diverse populations, optimizing trial parameters, estimating sample sizes, and informing enrichment strategies. Notably, these findings have been applied to calibrate and validate in silico trials, demonstrating utility in advancing computational approaches for HBV drug development. This approach enhances precision in predicting treatment outcomes and sets a precedent for leveraging MBMA in chronic hepatitis B research, paving the way for more effective strategies.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70164","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:39:03Z","timestamp":1765820343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Systematic Review and Model\u2010Based Meta\u2010Analysis of Pegylated\u2010Interferon\u2010\u03b1\u2010Induced\n                    <scp>HBsAg<\/scp>\n                    Loss in Chronic Hepatitis B Virus Infection"],"prefix":"10.1002","volume":"15","author":[{"given":"Nathan J.","family":"Hanan","sequence":"first","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9157","authenticated-orcid":false,"given":"Matthew L.","family":"Zierhut","sequence":"additional","affiliation":[{"name":"Certara  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Nader","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anadi","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Bridge Medical Consulting  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Bridge Medical Consulting  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Kumar","sequence":"additional","affiliation":[{"name":"Bridge Medical Consulting  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Dixon","sequence":"additional","affiliation":[{"name":"GSK  Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyeta","family":"Das","sequence":"additional","affiliation":[{"name":"GSK  Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy","family":"Magee","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[{"name":"GSK  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Gielen","sequence":"additional","affiliation":[{"name":"GSK  Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00124-8"},{"issue":"2","key":"e_1_2_9_3_1","first-page":"S191","article-title":"Health\u2010Related Quality of Life and Stigma Related to Chronic Hepatitis B: A Systematic Literature Review","volume":"75","author":"Gielen V.","year":"2021","journal-title":"Journal of Hepatology"},{"key":"e_1_2_9_4_1","volume-title":"Global Progress Report on HIV, Viral Hepatitis and Sexually Transmitted Infections, 2021. 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