{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:36Z","timestamp":1772160756845,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007110","name":"Schering-Plough","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007110","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,5]]},"abstract":"Abstract<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Triple therapy with peginterferon\/ribavirin (\n PR<\/jats:styled-content>\n ) plus an\n NS<\/jats:styled-content>\n 3 protease inhibitor has emerged as the standard\u2010of\u2010care for patients with chronic hepatitis C genotype\u20101. We provide a detailed safety analysis comparing\n PR<\/jats:styled-content>\n to boceprevir plus\n PR<\/jats:styled-content>\n (\n BOC<\/jats:styled-content>\n \/\n PR<\/jats:styled-content>\n ) across three phase 2\/3 studies.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n SPRINT<\/jats:styled-content>\n \u20101 was an open\u2010label phase 2 study in 595 treatment\u2010naive patients. In the two phase 3 studies, 1500 patients (1097 treatment\u2010naive,\n SPRINT<\/jats:styled-content>\n \u20102; 403 treatment\u2010failure,\n RESPOND<\/jats:styled-content>\n \u20102) were randomized to receive\n PR<\/jats:styled-content>\n alone, or one of two regimens where\n BOC<\/jats:styled-content>\n was added to\n PR<\/jats:styled-content>\n after a 4\u2010wk\n PR<\/jats:styled-content>\n lead\u2010in. In this analysis, the respective\n BOC<\/jats:styled-content>\n \/\n PR<\/jats:styled-content>\n and\n PR<\/jats:styled-content>\n arms were combined for all three trials. The benefit of shortened duration of treatment using response\u2010guided therapy (\n RGT<\/jats:styled-content>\n ) was also explored in the\n SPRINT<\/jats:styled-content>\n \u20102 trial.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the\n BOC<\/jats:styled-content>\n \u2010containing regimens compared with\n PR<\/jats:styled-content>\n . Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when\n BOC<\/jats:styled-content>\n was added to the\n PR<\/jats:styled-content>\n backbone. The proportions of patients reporting serious adverse events (AE), life\u2010threatening\n AE<\/jats:styled-content>\n s, and study drug discontinuation because of an\n AE<\/jats:styled-content>\n were similar in the\n PR<\/jats:styled-content>\n and\n BOC<\/jats:styled-content>\n \/\n PR<\/jats:styled-content>\n arms. In treatment\u2010naive patients,\n RGT<\/jats:styled-content>\n generally did not result in a lower frequency of common\n AE<\/jats:styled-content>\n s; however,\n RGT<\/jats:styled-content>\n led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant\n AE<\/jats:styled-content>\n s such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The safety profile of\n BOC<\/jats:styled-content>\n combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with\n RGT<\/jats:styled-content>\n significantly reduced the duration of\n AE<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.12300","type":"journal-article","created":{"date-parts":[[2013,8,2]],"date-time":"2013-08-02T10:10:04Z","timestamp":1375438204000},"page":"707-719","source":"Crossref","is-referenced-by-count":13,"title":["Overall safety profile of boceprevir plus peginterferon alfa\u20102b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2\/3 clinical trials"],"prefix":"10.1111","volume":"34","author":[{"given":"Michael P.","family":"Manns","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School (MHH) Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Jonathan","family":"McCone","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Mount Vernon Endoscopy Center Alexandria VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell N.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology South Florida Center of Gastroenterology Wellington FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Rossaro","sequence":"additional","affiliation":[{"name":"Department of Internal medicine and Gastroenterology University of California Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Schiff","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchel L.","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liver Institute of Virginia Bon Secours Health System Richmond and Newport News VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Bacon","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Saint Louis University School of Medicine St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Bourliere","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Gastroenterology Saint\u2010Joseph Hospital Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Sulkowski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savino","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine A.O. Fatebenefratelli e Oftalmico Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Balart","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Pierre","family":"Bronowicki","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010gastroenterology INSERM 954 Centre Hospitalier Universitaire de Nancy Universit\u00e9 de Lorraine Vandoeuvre les Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kwo","sequence":"additional","affiliation":[{"name":"Department of Medical Research Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Poordad","sequence":"additional","affiliation":[{"name":"Department of Medicine Texas Liver Institute\/University of Texas Health Science Center previously at Cedars\u2010Sinai Medical Center Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Felizarta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Private Practice Bakersfield CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Rajender","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans A.","family":"Helmond","sequence":"additional","affiliation":[{"name":"Department of Late Stage Development Hepatology Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather L.","family":"Sings","sequence":"additional","affiliation":[{"name":"Department of Global Scientific and Medical Publications, Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa D.","family":"Pedicone","sequence":"additional","affiliation":[{"name":"Former employee of Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Burroughs","sequence":"additional","affiliation":[{"name":"Department of Drug Safety Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford A.","family":"Brass","sequence":"additional","affiliation":[{"name":"Former employee of Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice K.","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Former employee of Merck Sharp & Dohme Corp. Whitehouse Station NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Vierling","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Surgery Baylor College of Medicine Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010494"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009482"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013086"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012912"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02707.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60934-8"},{"key":"e_1_2_6_8_1","unstructured":"Victrelis prescribing information. Availabe athttp:\/\/www.merck.com\/product\/usa\/pi_circulars\/v\/victrelis\/victrelis_pi.pdf. Accessed July 20 2012."},{"key":"e_1_2_6_9_1","volume-title":"I. FDA Antiviral Drugs Advisory Committee Meeting: Boceprevir Capsules (NDA 202\u2010258) 29\u2010March\u20102011 Briefing Document","author":"Merck and Co","year":"2012"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)61430-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197903000-00002"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811193392101"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_2_6_15_1","first-page":"323","article-title":"Skin rash during chronic hepatitis C therapy","volume":"6","author":"Veluru C","year":"2010","journal-title":"Gastroenterol Hepatol"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)60022-1"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12300","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12300","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T09:54:31Z","timestamp":1696240471000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,9]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1111\/liv.12300"],"URL":"https:\/\/doi.org\/10.1111\/liv.12300","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718367975.793494877","asserted-by":"object"}]},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,9]]}}}