Chronic Hepatitis C Treatment in Patients with Drug Injection History: Findings of the INTEGRATE Prospective, Observational Study.

INTRODUCTION: People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population. METHODS: INTEGRATE was a prospective, observational study investigating the effectiveness, safety, and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin (Peg-IFN/RBV) in patients with history of injecting drug use chronically infected with genotype 1 HCV. RESULTS: A total of 46 patients were enrolled and included in the intent-to-treat (ITT) population. Among heroin and/or cocaine users (n = 37; 80%), 22% reported use in the past month; 74% (34/46) of patients were on opioid substitution therapy in the pre-treatment phase, and 43% (20/46) discontinued HCV treatment prematurely. Sustained virologic response rate was 54% (25/46) in the ITT population and 74% (25/34) in the per protocol (evaluable-for-effectiveness) population. The main reason for failure in the ITT analysis was loss to follow-up (n = 8; 17%). Adverse events occurred in 91% (42/46) of patients. Mean patient-reported adherence to study drugs was >89% at Week 4, Week 12 and end of treatment. CONCLUSION: Despite a high rate of treatment discontinuation (including loss to follow-up), self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts. Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection, and highlight the need for improvements in patient support to boost retention in care and, in turn, help to prevent reinfection and transmission. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01980290. FUNDING: Janssen Pharmaceuticals

Final results of the telaprevir access program: Fibroscan values predict safety and efficacy in hepatitis c patients with advanced fibrosis or cirrhosis

Background: Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods: 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results: Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intentionto- treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions: FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. © 2015 Lepida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Safety and efficacy of telaprevir in treatment of a chronic hepatitis C in patients of the Russian population included in early access program study

Aim of investigation. HEP3002 is the international early access program of efficacy and safety estimation of telaprevir in combination to peginterferon alpha and ribavirin for patients with severe fibrosis or liver cirrhosis caused by hepatitis C virus (HCV) genotype 1. Efficacy and safety of this therapeutic mode were evaluated in intermediate analysis on 16-th week of treatment in 153 patients from Russia who have already reached the 16-th week of treatment or potentially can do so.Material and methods. The study has prospectively included 153 HCV infected patients (genotype 1), with bridging fibrosis or compensated liver cirrhosis who received treatment by telaprevir in combination to peginterferon-alpha and ribavirin for 12 wks with subsequent 12-or 36-week rate of antiviral therapy (AVT) by peginterferon alpha and ribavirin in relation to virologic response and fibrosis severity. Analysis has been carried out for intention to treat (ITT) populations with application of 16-th week AVT data.Results. Total of 153 patients have completed 12-week course of triple therapy and 4-week course of peginterferon-alpha and ribavirin treatment (48% cirrhotic patients, 97% – HCV-1b). The level of HCV RNA was undetectable both at the 4-th week, and at the 12-th week (extended rapid virologic response) in 42 (75%) of 56 previously untreated patients, in 34 (89%) of 38 with relapses after previous treatment, in 4 (57%) of 7 with previous incomplete response, in 22 (52%) of 42 with the previous zero response and in 7 (70%) of 10 with previous virologic breakthrough. Sustained virologic response was achieved in 73 (80%) of patients available for analysis (n=91). Most frequent adverse events of the 2-4 degrees, related to telaprevir, were anemia (63 patients, 41%), thrombocytopenia (15 patients, 10%) and skin rash (7 patients, 5%). For anemia treatment in 50 (33%) patients the doze of ribavirin has been reduced, erythropoietin was prescribed to 12 (8%) to patients and no blood transfusion was required; 10 (7%) patients have ahead of schedule stopped course of treatment by telaprevir in connection with development of anemia (6), thrombocytopenia (2) and occurrence of skin rash (2).Conclusion. In 153 patients with severe liver fibrosis caused by hepatitis C virus (genotype 1), on background of triple AVT with telaprevir high level of immediate virologic response and low level of the preterm treatment discontinuation was marked

Insulin resistance and response to telaprevir plus peginterferon alpha and ribavirin in treatment-naive patients infected with HCV genotype 1

Item does not contain fulltextOBJECTIVE: Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured by homoeostatic model assessment (HOMA), on virological response to telaprevir in Study C208. DESIGN: Overall, 161 HCV genotype 1-infected, treatment-naive patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36 weeks of peginterferon/ribavirin depending on on-treatment response criteria. The prognostic significance of several factors, including HOMA-insulin resistance (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24 weeks after treatment was explored by multiple regression analysis. RESULTS: Baseline HOMA-IR data were available for 147 patients; baseline characteristics were consistent with the overall population. Baseline HOMA-IR 4 was seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any time point) nor week 4 viral load decline were significantly influenced by baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density lipoprotein cholesterol level were predictive of sustained virological response (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was significantly lower in patients with sustained virological response than in those without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05). CONCLUSION: In this study, baseline HOMA-IR was not predictive of virological response to telaprevir in HCV genotype 1-infected, treatment-naive patients, while sustained virological response was associated with improved HOMA-IR. These results suggest that metabolic factors and insulin resistance do not have a significant effect on telaprevir-based treatment efficacy

Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C

Background and aim: Severe adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme to evaluate safety and efficacy of telaprevir (TVR) plus pegylated-interferon-\u3b1 (PEG-IFN\u3b1) and ribavirin (RBV) in patients with advanced liver fibrosis caused by HCV genotype 1 (HCV-1). Methods: 1782 patients with HCV-1 and bridging fibrosis or compensated cirrhosis were prospectively recruited from 16 countries worldwide, and treated with 12 weeks of TVR plus PEG-IFN/RBV, followed by 12 or 36 weeks of PEG-IFN and RBV (PR) alone dependent on virological response to treatment and previous response type. Results: 1587 patients completed 12 weeks of triple therapy and 4 weeks of PR tail (53% cirrhosis, 22% HCV-1a). By week 12, HCV RNA was undetectable in 85% of naives, 88% of relapsers, 80% of partial responders and 72% of null responders. Overall, 931 patients (59%) developed grade 1-4 anaemia (grade 3/4 in 31%), 630 (40%) dose reduced RBV, 332 (21%) received erythropoietin and 157 (10%) were transfused. Age and female gender were the strongest predictors of anaemia. 64 patients (4%) developed a grade 3/4 rash. Discontinuation of TVR due to AEs was necessary in 193 patients (12%). Seven patients died (0.4%, six had cirrhosis). Conclusions: In compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs

Low-density lipoprotein and other predictors of response with telaprevir-based therapy in treatment-experienced HCV genotype 1 patients: REALIZE study

BACKGROUND & AIMS: Predictors of response to treatment with peginterferon plus ribavirin are well established. In these post-hoc analyses of the REALIZE study, we sought to identify predictors of response for telaprevir-based triple therapy. METHODS: Patients from the REALIZE study with baseline data for all predictors evaluated (including baseline disease characteristics and demographics, prior treatment response and baseline laboratory assessments) were included in the post-hoc analyses (n = 465). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes. RESULTS: Sustained viral response (SVR) rates were 86% in prior relapsers, 63% in prior partial responders and 32% in prior null-responders. In the final multivariate analysis, baseline factors predicting SVR were prior response to treatment [Odds ratio (OR) = 2.80; 95% confidence interval (CI), 2.13-3.69], low-density lipoprotein (LDL) ( 652.6 mmol/L) (OR = 2.11; 95% CI, 1.52-2.93), HCV genotype (OR = 0.58; 95% CI, 0.36-0.93), and maximum alanine amino transferase and aspartate amino transferase (OR = 0.62; 95% CI, 0.40-0.97). CONCLUSIONS: Prior response to peginterferon plus ribavirin treatment and LDL levels are the main independent predictive markers of response with telaprevir-based triple therapy

Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1b and advanced liver disease

BACKGROUND & AIMS: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naive patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. METHODS: This phase II, open-label, single-arm, multicentre study included patients aged >/=18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. RESULTS: A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had >/=1 adverse event during treatment, including six (6%) patients with >/=1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. CONCLUSIONS: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory