{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:12:00Z","timestamp":1780337520418,"version":"3.54.1"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>In phase III studies, treatment with the once\u2010daily fixed\u2010dose combination tablet of ledipasvir\/sofosbuvir (LDV\/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV\u2010SOF with and without RBV. We analyzed treatment\u2010emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV\/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV\/SOF with RBV and 1,080 received LDV\/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index \u226530 kg\/m<jats:sup>2<\/jats:sup>, and 440 (23%) were treatment experienced. Treatment\u2010related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash\/pruritus. Patients receiving RBV with LDV\/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV\/SOF alone. Rates of treatment\u2010related serious AEs and discontinuations resulting from AEs were similarly low (&lt;1%) in both groups. The rate of SVR in those receiving RBV and those not receiving RBV was the same (97%). <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: LDV\/SOF plus RBV was associated with a greater incidence of AEs as well as concomitant medication use than LDV\/SOF alone. Use of RBV did not impact the efficacy of LDV\/SOF regimens in the ION phase III studies. (H<jats:sc>epatology<\/jats:sc> 2015;62:25\u201030)<\/jats:p>","DOI":"10.1002\/hep.27890","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T21:15:41Z","timestamp":1431378941000},"page":"25-30","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":79,"title":["Safety and tolerability of ledipasvir\/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials"],"prefix":"10.1097","volume":"62","author":[{"given":"Saleh A.","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Medicine,Johns Hopkins Hospital,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezam","family":"Afdhal","sequence":"additional","affiliation":[{"name":"Hepatology,Beth Israel Deaconess Medical Center,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Department of Medicine,Johann Wolfgang Goethe University,Frankfurt,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart C.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Gastroenterology,Henry Ford Health System,Detroit,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mangia","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Casa Sollievo della Sofferenza Hospital,San Giovanni Rotondo,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kwo","sequence":"additional","affiliation":[{"name":"Gastroenterology\u2010Hepatology,Indiana University School of Medicine,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fried","sequence":"additional","affiliation":[{"name":"Liver Center,University of North Carolina Health Care,Chapel Hill,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny C.","family":"Yang","sequence":"additional","affiliation":[{"name":"Liver Diseases,Gilead Sciences, Inc,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ding","sequence":"additional","affiliation":[{"name":"Liver Diseases,Gilead Sciences, Inc,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip S.","family":"Pang","sequence":"additional","affiliation":[{"name":"Liver Diseases,Gilead Sciences, Inc,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"McHutchison","sequence":"additional","affiliation":[{"name":"Liver Diseases,Gilead Sciences, Inc,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pound","sequence":"additional","affiliation":[{"name":"Indianapolis Gastroenterology Research Foundation,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Rajender","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Hospital of the University of Pennsylvania,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Marcellin","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Centre Hospitalier Universitaire Beaujon,Clichy\u2010sous\u2010Bois,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Care Network and Organ Care Research,Swedish Medical Center,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sulkowski","sequence":"additional","affiliation":[{"name":"Department of Medicine,Johns Hopkins Hospital,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"hep27890-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1517\/14740338.2011.559161","article-title":"Pegylated\u2010interferon\u2010alpha(2a) in clinical practice: how to manage patients suffering from side effects","volume":"10","year":"2011","journal-title":"Expert Opin Drug Saf"},{"key":"hep27890-bib-0004-20241017","first-page":"897","article-title":"Ribavirin as therapy for chronic hepatitis C. A randomized, double\u2010blind, placebo\u2010controlled trial","volume":"15","year":"1995","journal-title":"Ann Intern Med"},{"key":"hep27890-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jhep.2011.12.029","article-title":"A phase 1, randomized, placebo\u2010controlled, 3\u2010day, dose\u2010ranging study of GS\u20105885, an NS5A inhibitor, in patients with genotype 1 hepatitis C","volume":"57","year":"2012","journal-title":"J Hepatol"},{"key":"hep27890-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1053\/j.gastro.2013.11.007","article-title":"Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non\u2010nucleoside inhibitor GS\u20109669 against HCV genotype 1 infection","volume":"146","year":"2014","journal-title":"Gastroenterology"},{"key":"hep27890-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0140-6736(13)62121-2","article-title":"Sofosbuvir and ledipasvir fixed\u2010dose combination with and without ribavirin in treatment\u2010naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open\u2010label, randomised, phase 2 trial","volume":"383","year":"2014","journal-title":"Lancet"},{"key":"hep27890-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1056\/NEJMoa1316366","article-title":"Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1056\/NEJMoa1402454","article-title":"Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1056\/NEJMoa1402355","article-title":"Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1056\/NEJMoa1402338","article-title":"ABT\u2010450\/r\u2010ombitasvir and dasabuvir with or without ribavirin for HCV","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1056\/NEJMoa1306227","article-title":"Phase 2b trial of interferon\u2010free therapy for hepatitis C virus genotype 1","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1056\/NEJMoa1306218","article-title":"Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection","volume":"370","year":"2014","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S0140-6736(01)06102-5","article-title":"Peginterferon alfa\u20102b plus ribavirin compared with interferon alfa\u20102b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial","volume":"358","year":"2001","journal-title":"Lancet"},{"key":"hep27890-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1056\/NEJM199811193392101","article-title":"Interferon alfa\u20102b alone or in combination with ribavirin as initial treatment for chronic hepatitis C","volume":"339","year":"1998","journal-title":"N Engl J Med"},{"key":"hep27890-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/jvh.12158","article-title":"Ribavirin suppresses erythroid differentiation and proliferation in chronic hepatitis C patients","volume":"21","year":"2014","journal-title":"J Viral Hepat"},{"key":"hep27890-bib-0018-20241017","article-title":"Ledipasvir and sofosbuvir plus ribavirin for chronic hepatitis C virus infection in patients with advanced liver disease (SOLAR\u20101) before and after liver transplantation: a multicenter, randomized, open\u2010label, phase 2 study","year":"2015","journal-title":"Gastroenterology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27890","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.27890","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.27890","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201507000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:30:44Z","timestamp":1729211444000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201507000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,1]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27890","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,1]]},"assertion":[{"value":"2015-03-02","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-07","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}