Effectiveness of Simeprevir Plus Sofosbuvir, with or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

Mark S. Sulkowski, Hugo E. Vargas, Adrian M. Di Bisceglie, Alexander Kuo, K. Rajender Reddy, Joseph K. Lim, Giuseppe Morelli, Jama M. Darling, Jordan J. Feld, Robert S. Brown, Lynn M. Frazier, Thomas G. Stewart, Michael W. Fried, David R. Nelson, Ira M. Jacobson, N. Afdhal, I. Alam, Z. Ben-Ari, J. Bredfeldt, R. S. BrownR. T. Chung, J. Darling, W. Harlan, A. M. Di Bisceglie, R. C. Dickson, H. A. Elbeshbeshy, G. Everson, J. Feld, J. M. Fenkel, M. W. Fried, J. Galati, S. C. Gordon, M. Hassan, T. N. Hawkins, F. Hinestrosa, I. M. Jacobson, C. A. Kerr, A. Kuo, P. Y. Kwo, J. Levitsky, J. Lim, A. S. Lok, M. Mailliard, M. P. Manns, G. Morelli, A. J. Muir, D. Nelson, J. G. O'Leary, B. L. Pearlman, P. Pockros, HCV-TARGET Study Group

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET - a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment - a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalGastroenterology
Volume150
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
HCV-TARGET is an investigator-initiated study jointly sponsored by the University of Florida (Gainesville, FL) (principal investigator: Nelson), and the University of North Carolina (UNC) at Chapel Hill (Chapel Hill, NC) (principal investigator: Fried). It was funded in part by AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, and Vertex; funded in part by CTSA (Clinical and Translational Science Award) UF UL1TR000064 and the University of North Carolina 1UL1TR001111, funded in part by the National Institutes of Health Mid-Career Mentoring Award (K24 DK066144 to M.W.F.), and funded in part by the National Institutes of Health (K24DA034621 to M.S.S.).

Funding Information:
Conflicts of interest These authors disclose the following: Mark Sulkowski has received grants and personal fees from Gilead and Janssen; and has received personal fees from Achillion, and grants and personal fees from AbbVie, Merck, and BMS outside the submitted work; Dr Vargas has received grant funding from AbbVie, Gilead, Merck, and BMS; Adrian Di Bisceglie has received grant funding from Gilead, AbbVie, and Janssen during the conduct of the study, and consultant funds from Gilead and AbbVie outside the submitted work; Dr Kuo has received grant funding from Gilead; Dr Reddy has received grant funding from AbbVie, Merck, Gilead, Janssen, and Vertex; Dr Lim has received grant funding from AbbVie, Achillion, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, Glaxo-Smith Kline, Janssen, and Vertex, and consultant funds from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, and Merck; Dr Morelli has received grant funding from AbbVie, BMS, Gilead, Merck, Janssen, Vertex, Idenix, Conatus, and Salix; Dr Darling has received grant funding from Bristol-Myers Squibb; Dr Feld has received grant funding from AbbVie, Boehringer-Ingelheim, Gilead, Janssen, Merck, and Santaris; Dr Brown has received grant and consultant funding from Gilead and Janssen; Lynn Frazier has received grant and consultant funding from AbbVie, Gilead, Janssen, and Merck; Dr Fried has received grant funding from AbbVie, Bristol-Myers Squibb, Gilead, Glaxo, Merck, Vertex, and Genentech/Roche, and has received consultant funding from Genentech/Roche, Tibotec/Janssen, Vertex, Merck, Glaxo, Novartis, AbbVie, Gilead, and Bristol-Myers Squibb, in addition to funding from the National Institutes of Health for research; Dr Nelson has received grant funding from AbbVie, Gilead, BMS, Janssen, Merck, Vertex, and GSK; and Dr Jacobson has received grant funding from AbbVie, BMS, Gilead, Janssen, Merck, and Tobira, has received consultant and advisor funding from AbbVie, Achillion, Alnylam, BMS, Enanta, Gilead, Janssen, and Merck, and also has received funding from AbbVie, BMS, Gilead, and Janssen for serving on the speakers bureau. The remaining author discloses no conflicts.

Funding Information:
Funding HCV-TARGET is an investigator-initiated study jointly sponsored by the University of Florida (Gainesville, FL) (principal investigator: Nelson), and the University of North Carolina (UNC) at Chapel Hill (Chapel Hill, NC) (principal investigator: Fried). It was funded in part by AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, and Vertex; funded in part by CTSA (Clinical and Translational Science Award) UF UL1TR000064 and the University of North Carolina 1UL1TR001111, funded in part by the National Institutes of Health Mid-Career Mentoring Award (K24 DK066144 to M.W.F.), and funded in part by the National Institutes of Health (K24DA034621 to M.S.S.).

Publisher Copyright:
© 2016 AGA Institute.

Keywords

  • Chronic Hepatitis
  • Direct-Acting Agent
  • NS3/4A Protease Inhibitor
  • NS5B

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