Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection

Fried, Michael; Shiffman, Mitchell L.; Reddy, K. Rajender; Smith, Coleman I.; Marinos, George; Gonçales, Fernando Lopes; Häussinger, Dieter; Diago, M.; Carosi, Giampiero; Dhumeaux, Daniel; Craxı̀, Antonio; Lin, Amy; Hoffman, Joseph H.; Yu, Jianhua

doi:10.1056/nejmoa020047

Cited by 5,831 publications

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“…15 Consistent with other studies, EVR was the most reliable predictor of nonresponse with a negative predictive value of 98% in the standard therapy group. 1,20,21 Interestingly, the data also suggested that induction dosing, although associated with higher EVR, did not significantly change the predictive value of virological response parameters at week 4 or 12 for achieving an SVR.…”

Section: Discussionmentioning

confidence: 87%

“…The relationships between interferon dose and early phase HCV kinetics, including phase I and II slope and time to undetectable HCV RNA, 12,13 and early virological responses and SVR support such a rationale. 1,[14][15][16] Studies utilizing induction therapy with (peg)interferon in patients with genotype 1 CHC have yielded mixed results, with some patients demonstrating an enhanced SVR 4,5 and others not. [6][7][8][9][10][11] However, there has been no published randomized trial of high-dose induction therapy with peginterferon alfa-2a/b (PEG-IFN␣-2a/b) in a large population of treatment-naïve patients with genotype 1 CHC.…”

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confidence: 99%

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Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial

Roberts¹,

Weltman²,

Crawford³

et al. 2009

Hepatology

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This study tested the hypothesis that high-dose peginterferon alfa-2a (PEG-IFN␣-2a) for the first 12 weeks would increase early and sustained virological response (SVR) rates in patients with chronic hepatitis C genotype 1. Eight hundred ninety-six patients were randomized 1:1 to 360 g (n ‫؍‬ 448) or 180 g (n ‫؍‬ 448) PEG-IFN␣-2a weekly plus ribavirin at 1000-1200 mg/day for 12 weeks, followed by 36 weeks of 180 g PEG-IFN␣-2a weekly plus ribavirin at 1000-1200 mg/day with 871 patients evaluable for the intention-to-treat analysis. Virological responses were assessed by TaqMan (limit of detection 15 IU/mL) at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (SVR). Undetectable hepatitis C virus RNA rates were significantly higher among patients receiving high-dose induction therapy at week 4 (36% versus 26%, P < 0.005), week 8 (61% versus 50%, P < 0.005), and week 12 (74% versus 62%, P < 0.005). However, SVR was not significantly different between patients receiving high-dose (53%) and standard (50%) therapy. Significant baseline prognostic factors for SVR included age, sex, race, histological stage, and viral load. SVR was considerably higher among patients with no or minimal fibrosis (64% and 60%, respectively) compared to those with severe fibrosis/cirrhosis (28% and 24%, respectively). The frequency of serious adverse events and drug discontinuations were similar in both groups, whereas PEG-IFN dose modification, weight and appetite reduction, and grade IV neutropenia were significantly higher in the induction arm.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial

Roberts¹,

Weltman²,

Crawford³

et al. 2009

Hepatology

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“…Newer regimens such as pegylated interferon-a in combination with ribavirin result in viral eradication in approximately 50% of individuals with genotype-1 infections and 70% of those with non-1 type infections. 13,14 In addition to viral (ie, viral genotypes) and environmental/behavioural factors (ie, coinfections or excessive alcohol intake), host genetic factors are believed to exert an impact on the outcome of HCV infection. Studies among monozygotic twins suggest that host genetic factors may account for 50% or more of the variability in the major outcomes in infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Host genetic determinants in hepatitis C virus infection

2004

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In addition to viral and environmental/behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in hepatitis C virus (HCV) infection. This paper reviews the literature with respect to studies of host genetic determinants of HCV outcome and attempts to highlight trends and synthesise findings. With respect to the susceptibility to HCV infection, several studies have replicated associations of the HLA class II alleles DQB1*0301 and DRB1*11 with selflimiting infection predominantly in Caucasian populations. Meta-analyses yielded summary estimates of 3.0 (95% CI: 1.8-4.8) and 2.5 (95% CI: 1.7-3.7) for the effects of DQB1*0301 and DRB1*11 on self-limiting HCV, respectively. Studies of genetics and the response to interferon-based therapies have largely concerned single-nucleotide polymorphisms and have been inconsistent. Regarding studies of genetics and the progression of HCV-related disease, there is a trend with DRB1*11 alleles and less severe disease. Studies of extrahepatic manifestations of chronic HCV have shown an association between DQB1*11 and DR3 with the formation of cryoglobulins. Some important initial observations have been made with respect to genetic determinants of HCV outcome. Replication studies are needed for many of these associations, as well as biological data on the function of many of these polymorphisms.

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“…Across six phase 3 studies of OBV/PTV/r + DSV + RBV, RBV dose reductions were required in only 6.5% of patients, compared with approximately 20% of patients receiving pegIFN/RBV therapy in past studies 1, 2. Head‐to‐head studies have recently reported RBV dose reductions to be lower in patients receiving OBV/PTV/r + DSV + RBV compared with those receiving the first‐generation protease inhibitor, telaprevir, in combination with pegIFN/RBV 17…”

Section: Discussionmentioning

confidence: 99%

“…In combination with standard interferon and pegylated interferon (pegIFN), ribavirin (RBV) has been shown to significantly decrease the risk of post‐treatment viral relapse and increase rates of sustained virological response (SVR) in patients with hepatitis C virus (HCV) infection 1, 2. Despite improving the efficacy of IFN‐based therapy, RBV is associated with haemolytic anaemia,3, 4 a phenomenon driven by accumulation of RBV in erythrocytes and oxidative damage within the red blood cells 5.…”

Section: Introductionmentioning

confidence: 99%

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Feld

Bernstein

Younes

et al. 2018

Liver International

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Background & AimsSome individuals with hepatitis C virus infection treated with direct‐acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus‐infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.MethodsWe performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.ResultsOf 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post‐treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).ConclusionsRibavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post‐treatment. Patients with low baseline haemoglobin should be monitored for on‐treatment anaemia.

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Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection

Cited by 5,831 publications

References 19 publications

Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial

Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial

Host genetic determinants in hepatitis C virus infection

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

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