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

HCV-TARGET Study Group

Research output: Contribution to journalArticle

120 Citations (Scopus)

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

Fingerprint

Ribavirin
Hepacivirus
Genotype
Infection
Therapeutics
Observational Studies
Fibrosis
Cohort Studies
Logistic Models
Simeprevir
Sofosbuvir
Selection Bias
Sleep Initiation and Maintenance Disorders
North America
Exanthema
Protease Inhibitors
Nausea
Interferons
Fatigue
Headache

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Effectiveness of Simeprevir Plus Sofosbuvir, with or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection. / HCV-TARGET Study Group.

In: Gastroenterology, Vol. 150, No. 2, 01.02.2016, p. 419-429.

Research output: Contribution to journalArticle

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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.",
keywords = "Chronic Hepatitis, Direct-Acting Agent, NS3/4A Protease Inhibitor, NS5B",
author = "{HCV-TARGET Study Group} and Sulkowski, {Mark S.} and Vargas, {Hugo E.} and {Di Bisceglie}, {Adrian M.} and Alexander Kuo and Reddy, {K. Rajender} and Lim, {Joseph K.} and Giuseppe Morelli and Darling, {Jama M.} and Feld, {Jordan J.} and Brown, {Robert S.} and Frazier, {Lynn M.} and Stewart, {Thomas G.} and Fried, {Michael W.} and Nelson, {David R.} and Jacobson, {Ira M.} and N. Afdhal and I. Alam and Z. Ben-Ari and J. Bredfeldt and Brown, {R. S.} and Chung, {R. T.} and J. Darling and W. Harlan and {Di Bisceglie}, {A. M.} and Dickson, {R. C.} and Elbeshbeshy, {H. A.} and G. Everson and J. Feld and Fenkel, {J. M.} and Fried, {M. W.} and J. Galati and Gordon, {S. C.} and M. Hassan and Hawkins, {T. N.} and F. Hinestrosa and Jacobson, {I. M.} and Kerr, {C. A.} and A. Kuo and Kwo, {P. Y.} and J. Levitsky and J. Lim and Lok, {A. S.} and Mailliard, {Mark E} and Manns, {M. P.} and G. Morelli and Muir, {A. J.} and D. Nelson and O'Leary, {J. G.} and Pearlman, {B. L.} and P. Pockros",
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TY - JOUR

T1 - Effectiveness of Simeprevir Plus Sofosbuvir, with or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

AU - HCV-TARGET Study Group

AU - Sulkowski, Mark S.

AU - Vargas, Hugo E.

AU - Di Bisceglie, Adrian M.

AU - Kuo, Alexander

AU - Reddy, K. Rajender

AU - Lim, Joseph K.

AU - Morelli, Giuseppe

AU - Darling, Jama M.

AU - Feld, Jordan J.

AU - Brown, Robert S.

AU - Frazier, Lynn M.

AU - Stewart, Thomas G.

AU - Fried, Michael W.

AU - Nelson, David R.

AU - Jacobson, Ira M.

AU - Afdhal, N.

AU - Alam, I.

AU - Ben-Ari, Z.

AU - Bredfeldt, J.

AU - Brown, R. S.

AU - Chung, R. T.

AU - Darling, J.

AU - Harlan, W.

AU - Di Bisceglie, A. M.

AU - Dickson, R. C.

AU - Elbeshbeshy, H. A.

AU - Everson, G.

AU - Feld, J.

AU - Fenkel, J. M.

AU - Fried, M. W.

AU - Galati, J.

AU - Gordon, S. C.

AU - Hassan, M.

AU - Hawkins, T. N.

AU - Hinestrosa, F.

AU - Jacobson, I. M.

AU - Kerr, C. A.

AU - Kuo, A.

AU - Kwo, P. Y.

AU - Levitsky, J.

AU - Lim, J.

AU - Lok, A. S.

AU - Mailliard, Mark E

AU - Manns, M. P.

AU - Morelli, G.

AU - Muir, A. J.

AU - Nelson, D.

AU - O'Leary, J. G.

AU - Pearlman, B. L.

AU - Pockros, P.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - Chronic Hepatitis

KW - Direct-Acting Agent

KW - NS3/4A Protease Inhibitor

KW - NS5B

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DO - 10.1053/j.gastro.2015.10.013

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