Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection

McHutchison, John G.; Lawitz, Eric; Shiffman, Mitchell L.; Muir, Andrew J.; Galler, Greg; McCone, Jonathan; Nyberg, Lisa M.; Lee, William M.; Ghalib, Reem; Schiff, Eugene R.; Galati, Joseph; Bacon, Bruce R.; Davis, Mitchell; Mukhopadhyay, Pabak; Koury, Kenneth; Noviello, Stephanie; Pedicone, Lisa D.; Brass, Clifford A.; Albrecht, Janice K.; Sulkowski, Mark S.

doi:10.1056/nejmoa0808010

Cited by 1,078 publications

(968 citation statements)

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“…Treatment was discontinued because of treatment failure in patients with detectable HCV RNA and a <2-log 10 decrease in HCV RNA from the baseline at week 12 and in patients with detectable HCV RNA at week 24. 26,27 Laboratory Assessments. Fasting LDL and HDL levels were measured at screening visit 2 (baseline), in treatment weeks 12, 24, 36, and 48, and in follow-up week 24.…”

Section: Methodsmentioning

confidence: 99%

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

et al. 2010

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Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response. To determine whether baseline LDL or HDL levels and statin use affect SVR rates, we retrospectively evaluated the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial, in which 3070 treatment-naive, hepatitis C virus (HCV) genotype 1-infected patients were treated for up to 48 weeks in one of the following arms: (1) peginterferon (PEG-IFN) alfa-2b at 1.5 lg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa2b at 1.0 lg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 lg/week with RBV at 1000 to 1200 mg/day. Virological responses were assessed by pretreatment statin use and baseline elevated LDL levels (!130 mg/dL) or low HDL levels (<40 mg/dL for men and <50 mg/dL for women). In 1464 patients with baseline elevated LDL levels or low HDL levels, the SVR rate was significantly higher than that in patients with normal levels (44.9% versus 34.0%, P < 0.001). In 66 patients receiving a statin pretreatment, the SVR rate was higher than the rate of those not receiving it (53.0% versus 39.3%, P 5 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) 5 1.6, 95% confidence interval (CI) 5 1.4-1.8, P < 0.001], a low HDL level (OR 5 0.5, 95% CI 5 0.3-0.8, P 5 0.004), and statin use (OR 5 2.0, 95% CI 5 1.1-3.7, P 5 0.02) were independently associated with SVR. Conclusion: Baseline elevated LDL levels or low HDL levels and preemptive statin usage were associated with higher SVR rates. Prospective studies may be considered to explore the biological impact of these factors on HCV RNA replication and treatment response. (HEPATOLOGY 2010;52:864-874)

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Section: Methodsmentioning

confidence: 99%

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

et al. 2010

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“…Moreover, reducing RBV dose prior to achieve HCV RNA below the LLOQ had no negative impact on achieving SVR12. Previous studies evaluating pegIFN/RBV therapy also concluded that mild to moderate RBV dose reductions do not adversely affect SVR rates 18, 19…”

Section: Discussionmentioning

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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“…Our results for genotype 1 are similar to those reported in registration clinical trials, however, SVR for genotypes 2 and 3 were lower than those demonstrated in pharmaceutical trials. [8][9][10][11] Previous multi-centre, open-label community trials in the United States and Canada had much lower outcomes across all genotypes, when compared to the drug registration trials. 26,27 These lower results have been suggested to be due to the large number of patients included in the analysis who were lost to follow-up.…”

Section: Side Effects and Treatment Cessationmentioning

confidence: 99%

“…37 Our study also addressed side effects experienced from the PEG-IFN and RBV combination treatment, a factor not significantly analyzed in similar studies. [8][9][10]13,21,23 While 81.6% of the treated patients in this study experienced some side effects, only 8.4% ceased treatment prematurely. These discontinuation rates are better than those reported in some registration clinical trials, which range from 14 to 21%, 8,10,11 and are similar to other cohort studies in clinical practice.…”

Section: Side Effects and Treatment Cessationmentioning

confidence: 99%

“…7 Published clinical trials of the treatment of HCV tend to have more favorable outcomes and are largely multicenter prospective pharmaceutical registration trials, which assess treatment response in treatment-na € õve patients with strict exclusion criteria and differences in treatment conditions. [8][9][10][11][12] To date, there have only been 2 single-centered retrospective audits of HCV treatment in Australia, 13,14 and one multi-centre study, 15 of 'real-world' patients treated in normal clinical practice. Often single hospitals have limited nursing and medical resources compared to large multinational clinical trials, which may affect patient retention in HCV therapy.…”

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confidence: 99%

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Hepatitis C Virus Treatment in the ‘Real-World’: How Well Do ‘Real’ Patients Respond?

Friedman

Green

Weber

et al. 2014

Journal of Clinical and Experimental Hepatology

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Background: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. Objectives: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. Methods: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. Results: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). Conclusions: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials. ( J CLIN EXP HEPATOL 2014;4:214-220)

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Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection

Abstract: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.gov number, NCT00081770.)

Cited by 1,078 publications

References 18 publications

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

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

Hepatitis C Virus Treatment in the ‘Real-World’: How Well Do ‘Real’ Patients Respond?

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