{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T01:28:32Z","timestamp":1722907712490},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Ribavirin exposure after the first dose (D<jats:sub>0<\/jats:sub>AUC<jats:sub>0\u20134h<\/jats:sub>) &gt;1755 mcg\u00b7h<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup> is predictive of sustained virological response (SVR) in patients with hepatitis C treated with peginterferon and ribavirin. The aim of this study was to test the benefit of ribavirin early dose adjustment based on this target in na\u00efve patients infected with genotype 1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>A multicenter randomized controlled trial with two parallel groups; fixed-dose (FD) group: standard of care in 2010\u20132011, ie, peginterferon-\u03b12a 180 mcg\u00b7wk<jats:sup>\u22121<\/jats:sup> and weight-based ribavirin 1000\u20131200 mg\/d during 48 weeks; adapted-dose (AD) group: increase of ribavirin dose if D<jats:sub>0<\/jats:sub>AUC<jats:sub>0\u20134h<\/jats:sub> &lt;1755 mcg\u00b7h<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>A total of 221 patients were included, 110 in the AD group and 111 in the FD group with similar baseline characteristics. In the perprotocol analysis, SVR was higher in the AD group (55.1% versus 40.4%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.042), especially in patients with D<jats:sub>0<\/jats:sub>AUC<jats:sub>0\u20134h<\/jats:sub> &lt;1755 mcg\u00b7h<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup> (54.3% versus 31.9%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.029). In the intention-to-treat analysis, the difference was not significant (50% versus 41%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.197). Ribavirin trough concentrations (C0s) at week 4 of treatment (intention-to-treat analysis) were higher in patients achieving SVR (2.06 versus 1.72 mg\/L, <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.003). In the subgroup of patients with AUC<jats:sub>0\u20134h<\/jats:sub> &lt;1755 mcg\u00b7h<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup>, 46% of patients with AD achieved a C0 &gt;2.0 mg\/L versus 22% of patients with FD (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.013). Grade 1 anemia (but not other grades) was more frequent in the AD group (70% versus 48%, <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.001). The number of dose reductions or discontinuation of ribavirin was similar in both groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Early ribavirin dose adjustment increases SVR in patients underexposed to ribavirin without increasing grade II-IV anemia. Such a strategy could be useful in patients with no access to new antiviral drugs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000332","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T12:30:25Z","timestamp":1472041825000},"page":"684-692","source":"Crossref","is-referenced-by-count":2,"title":["Efficiency and Safety of an Early Dose Adjustment of Ribavirin in Patients Infected With Hepatitis C Underexposed to the Drug and Treated With Peginterferon Ribavirin"],"prefix":"10.1097","volume":"38","author":[{"given":"V\u00e9ronique","family":"Loustaud-Ratti","sequence":"first","affiliation":[{"name":"Service d'H\u00e9patogastroent\u00e9rologie, H\u00f4pital Dupuytren, Limoges;"},{"name":"INSERM, U850, Universit\u00e9 de Limoges, F-87000 Limoges;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Maynard","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patologie, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Thevenon","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patologie, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Pradat","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patologie, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Rousseau","sequence":"additional","affiliation":[{"name":"INSERM, U850, Universit\u00e9 de Limoges, F-87000 Limoges;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Alain","sequence":"additional","affiliation":[{"name":"INSERM, U1092, Universit\u00e9 de Limoges, F-87000 Limoges;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Deny","sequence":"additional","affiliation":[{"name":"U1052, INSERM, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Claude","family":"Gagnieu","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie Sp\u00e9cialis\u00e9e, H\u00f4pital E. Herriot, Hospices Civils de Lyon, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Tran","sequence":"additional","affiliation":[{"name":"P\u00f4le de R\u00e9f\u00e9rence H\u00e9patite C, H\u00f4pital Archet 2, Nice;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Th\u00f4ng","family":"Dao","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9pato-gastro-ent\u00e9rologie et nutrition, H\u00f4pital de la C\u00f4te de Nacre, CAEN;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Silvain","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9pato-gastro-ent\u00e9rologie, Centre Hospitalier Universitaire de Poitiers;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Lunel-Fabiani","sequence":"additional","affiliation":[{"name":"D\u00e9partement Biologie des agents infectieux et pharmacotoxicologie-Virologie, Centre Hospitalier Universitaire d'Angers, Angers;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Picard","sequence":"additional","affiliation":[{"name":"INSERM, U850, Universit\u00e9 de Limoges, F-87000 Limoges;"},{"name":"Laboratoire de Pharmacologie M\u00e9dicale, Universit\u00e9 de Limoges."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ir\u00e8ne","family":"Zublena","sequence":"additional","affiliation":[{"name":"Direction de la Recherche Clinique et de l'Innovation, Hospices Civils de Lyon, Lyon, France; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Marquet","sequence":"additional","affiliation":[{"name":"INSERM, U850, Universit\u00e9 de Limoges, F-87000 Limoges;"},{"name":"Laboratoire de Pharmacologie M\u00e9dicale, Universit\u00e9 de Limoges."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Trepo","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patologie, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, Lyon;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the RIBAJUSTE Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMe1401508","article-title":"Therapy for hepatitis C\u2014the costs of success","volume":"370","author":"Hoofnagle","year":"2014","journal-title":"N Engl J Med."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3851\/IMP2127","article-title":"New antiviral therapies in the management of HCV infection","volume":"17","author":"Farnik","year":"2012","journal-title":"Antivir Ther."},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S1473-3099(12)70060-9","article-title":"Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care","volume":"12","author":"Pearlman","year":"2012","journal-title":"Lancet Infect Dis."},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1056\/NEJMoa020047","article-title":"Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection","volume":"347","author":"Fried","year":"2002","journal-title":"N Engl J Med."},{"key":"R5-20230814","doi-asserted-by":"crossref","first-page":"346","DOI":"10.7326\/0003-4819-140-5-200403020-00010","article-title":"Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose","volume":"140","author":"Hadziyannis","year":"2004","journal-title":"Ann Intern Med."},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S0140-6736(01)06102-5","article-title":"Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial","volume":"358","author":"Manns","year":"2001","journal-title":"Lancet"},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1053\/j.gastro.2006.07.022","article-title":"Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin","volume":"131","author":"Bronowicki","year":"2006","journal-title":"Gastroenterology"},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1097\/FTD.0000000000000210","article-title":"High-dose ribavirin enhances early virological response in hepatitis C genotype 1-infected patients","volume":"37","author":"Lindahl","year":"2015","journal-title":"Ther Drug Monit."},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/hep.20563","article-title":"High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C","volume":"41","author":"Lindahl","year":"2005","journal-title":"Hepatology"},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1067\/mcp.2002.127112","article-title":"Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models","volume":"72","author":"Jen","year":"2002","journal-title":"Clin Pharmacol Ther."},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1128\/AAC.47.1.124-129.2003","article-title":"Ribavirin quantification in combination treatment of chronic hepatitis C","volume":"47","author":"Larrat","year":"2003","journal-title":"Antimicrob Agents Chemother."},{"key":"R12-20230814","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1002\/hep.22217","article-title":"Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C","volume":"47","author":"Loustaud-Ratti","year":"2008","journal-title":"Hepatology"},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1177\/135965350801300401","article-title":"Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients","volume":"13","author":"Maynard","year":"2008","journal-title":"Antivir Ther."},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1128\/AAC.01399-09","article-title":"Plasma ribavirin trough concentrations at week 4 predict hepatitis C virus (HCV) relapse in HIV-HCV-coinfected patients treated for chronic hepatitis C","volume":"54","author":"Morello","year":"2010","journal-title":"Antimicrob Agents Chemother."},{"key":"R15-20230814","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1159\/000081741","article-title":"Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C","volume":"48","author":"Arase","year":"2005","journal-title":"Intervirology"},{"key":"R16-20230814","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.dld.2011.04.002","article-title":"Pharmacological exposure to ribavirin: a key player in the complex network of factors implicated in virological response and anaemia in hepatitis C treatment","volume":"43","author":"Loustaud-Ratti","year":"2011","journal-title":"Dig Liver Dis."},{"key":"R17-20230814","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/FTD.0b013e3181a665e3","article-title":"Feasibility of ribavirin therapeutic drug monitoring in hepatitis C","volume":"31","author":"Sauvage","year":"2009","journal-title":"Ther Drug Monit."},{"key":"R18-20230814","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1089\/jir.2015.0131","article-title":"Does epoetin beta still have a place in peginterferon alpha-2a plus ribavirin treatment strategies for chronic hepatitis C?","volume":"36","author":"Veillon","year":"2016","journal-title":"J Interferon Cytokine Res."},{"key":"R19-20230814","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/ajg.2012.48","article-title":"Update on the management and treatment of hepatitis C virus infection: recommendations from the Department of Veterans Affairs hepatitis C resource center Program and the national hepatitis C Program Office","volume":"107","author":"Yee","year":"2012","journal-title":"Am J Gastroenterol."},{"key":"R20-20230814","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000090942","article-title":"Ribavirin levels and haemoglobin decline in early virological responders and non-responders to hepatitis C virus combination therapy","volume":"76","author":"Donnerer","year":"2006","journal-title":"Pharmacology"},{"key":"R21-20230814","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1177\/135965350701200815","article-title":"Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients","volume":"12","author":"Crespo","year":"2007","journal-title":"Antivir Ther."},{"key":"R22-20230814","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1046\/j.1365-2036.2002.01331.x","article-title":"Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in \u201creal world\u201d patients with chronic hepatitis C","volume":"16","author":"Gaeta","year":"2002","journal-title":"Aliment Pharmacol Ther."},{"key":"R23-20230814","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1097\/MEG.0b013e32833e784d","article-title":"Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment","volume":"22","author":"Van","year":"2010","journal-title":"Eur J Gastroenterol Hepatol."},{"key":"R24-20230814","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nature08825","article-title":"ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C","volume":"464","author":"Fellay","year":"2010","journal-title":"Nature"},{"key":"R25-20230814","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1053\/j.gastro.2010.06.016","article-title":"Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction","volume":"139","author":"Thompson","year":"2010","journal-title":"Gastroenterology"},{"key":"R27-20230814","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1093\/jac\/dkv122","article-title":"Serum and cellular ribavirin pharmacokinetic and concentration-effect analysis in HCV patients receiving sofosbuvir plus ribavirin","volume":"70","author":"Rower","year":"2015","journal-title":"J Antimicrob Chemother."},{"issue":"suppl l","key":"R28-20230814","first-page":"1160A","article-title":"Characteristics of HCV-Infected patients with cirrhosis requiring ribavirin dose reduction during treatment with direct-acting antivirals. 65th Annual Meeting of the AASLD","volume":"60","author":"Jacobson","year":"2014","journal-title":"Hepatology"}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201612000-00006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T18:09:53Z","timestamp":1692036593000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201612000-00006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000332","relation":{},"ISSN":["0163-4356"],"issn-type":[{"type":"print","value":"0163-4356"}],"subject":[],"published":{"date-parts":[[2016,12]]}}}