Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis

HCV-TARGET Study Group

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10 Scopus citations

Abstract

Background & Aims: We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). Methods: We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. Results: The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46–6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59–7.00) were associated with SVR12. Conclusions: In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.

Original languageEnglish (US)
Pages (from-to)1811-1819.e4
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number11
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
Funding HCV-TARGET is an investigator-initiated study jointly sponsored by the University of Florida, Gainesville, FL (PI: Nelson) and the University of North Carolina at Chapel Hill, Chapel Hill, NC (PI: Fried). It was funded in part by AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, and Vertex and funded in part by CTSA UF UL1TR000064. Dr Fried was funded in part by NIH Mid-Career Mentoring Award K24 DK066144.

Funding Information:
Conflicts of interest These authors disclose the following: J.K.L. received grant funding from BMS, Conatus, Genfit, Gilead, Hologic, and Intercept (all to institution) and was a consultant to AbbVie, BMS, and Gilead. A.M.L. received grant funding from BMS, Genfit, Gilead, Hologic, Intercept, and Prometheus (all to institution) and was consultant to AbbVie, BMS, and Gilead. M.S. received grant funding from AbbVie, BMS, Conatus, CymaBay, Exalenz, Galectin, Genfit, Gilead, Intercept, Immuron, Merck, NGMBio, Novartis, and Shire; was a consultant to Optum Rx; received sponsored lectures/honoraria from AbbVie, BMS, Gilead, Intercept, and Merck; and was on Expert Testimony/Advisory Board to AbbVie, BMS, Gilead, Intercept, and Merck. A.S.L. received grant funding from BMS, Gilead, and Target Pharma. S.Z. was a consultant for AbbVie, BMS, Gilead, Intercept, Janssen, and Merck; and received sponsored lectures/honoraria from AbbVie, BMS, Gilead, and Merck. N.A.T. received grant funding from Gilead, BMS, AbbVie, and Merck; was a consultant to Gilead and Merck; received sponsored lectures/honoraria to CCO Hepatitis, Practice Point Communications, Focus Medical Communications, Annenberg Center for Health Sciences, PRIME Education Inc; and received other support from research grants from HIH. J.S.P. was a consultant to Gilead and AbbVie; and received sponsored lectures/honoraria from Gilead, AbbVie, and Merck. C.S.L. received grant funding from AbbVie and Gilead. J.G. received grant funding from AbbVie, BMS, Gilead, Janssen, Merck, Sangamo, Theratechnologies, and ViiV/GlaxoSmithKline; and was on expert testimony/advisory board to BMS, Gilead, Merck, Theratechonologies, and ViiV Healthcare. A.K. received grant funding from Gilead and received sponsored lectures/honoraria from Gilead. P.J.P. received grant funding from Gilead, AbbVie, Merck, Intercept, and Genfit; was a consultant to Gilead, AbbVie, Merck, Intercept, and Genfit; and received sponsored lectures/honoraria to Gilead, AbbVie, Merck, and Intercept. M.W.F. received grant funding from AbbVie, BMS, Gilead, and Merck; was a consultant for AbbVie, BMS, Gilead, Merck, and TARGET Pharmasolutions; is a Stockholder with TARGET Pharmasolutions; and received other research grants from NIH. D.R.N. received grant funding from AbbVie, Gilead, BMS, Janssen, and Merck; and is a stockholder of TARGET Pharmasolutions. Z.B.A. was a consultant to AbbVie, Gilead, Merck, Janssen, and BMS; and received sponsored lectures/honoraria to AbbVie, Gilead, Merck, Janssen, and BMS. The remaining authors disclose no conflicts.

Publisher Copyright:
© 2018 AGA Institute

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • HCV-TARGET
  • Liver Disease
  • Real World
  • Therapy
  • Viral Hepatitis

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