SVR12 Rates In Patients Research Articles

Peg-interferon plus ribavirin with or without boceprevir or telaprevir for HCV genotype 1: a meta-analysis on the role of response predictors.

Background & aimTo compare the efficacy of pegylated-interferon (Peg-IFN) α-2a or α-2b and ribavirin given as dual therapy versus triple therapy (Peg-IFN and ribavirin plus boceprevir or telaprevir) in patients with HCV-1 chronic hepatitis naïve for anti-HCV therapy or relapsers to dual therapy in relation to the presence of constitutional, clinical and virological predictors of treatment response.MethodsIncluded in the meta-analysis were studies meeting these criteria: original data from randomized trials on the efficacy of dual versus triple therapy in therapy-naïve patients or relapsers; at least one primary outcome clearly defined: sustained virological response in patients with or without rapid virological response (RVR), with genotype 1a or 1b, low or high HCV load, IL28-B CC or non-CC genotype, mild or severe fibrosis; odds ratio estimates of relative risk (RR) and 95% confidence intervals; English language; and published up to the end of June 2013.ResultsSeven original studies met the inclusion criteria, allowing a meta-analysis on 3,652 patients. Triple therapy was more effective than dual, regardless of IL-28B genotype, HCV sub-genotype, liver fibrosis, and baseline HCV load. In 1,045 patients who achieved RVR, SVR was more frequently achieved with dual therapy (RR = 1.11; p = 0.002) than triple. The same results were achieved when only the therapy-naïve patients were considered.ConclusionsTriple therapy provides a significantly higher SVR rate than dual therapy, but dual therapy obtains a significantly higher SVR rate in patients with RVR. The data stress the clinical importance of a 4-week lead-in phase in direct-acting antiviral-based treatment.

Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor

The new standard of care for treatment-naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients. Treatment-naïve, noncirrhosis patients infected with genotype-1 HCV and a low viral load at baseline were considered for inclusion (n = 233). After 4 weeks of lead-in therapy with peginterferon α-2b and ribavirin, 101 patients (48%) had a rapid virologic response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and were eligible to participate. Patients were randomized 1:1 to 20 weeks of additional therapy with peginterferon α-2b and ribavirin (double therapy) or to 24 weeks of peginterferon α-2b, ribavirin, and boceprevir (triple therapy). There was no significant difference in rates of SVR-12 in patients treated with double versus triple therapy. This similarity persisted regardless of viral subtype (genotype 1a or 1b), interleukin (IL)-28b genotype (CC or non-CC), or ethnicity (African American versus non-Hispanic white). Protease inhibitor therapy could be obviated in genotype 1-infected treatment-naïve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin.

Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection

The combination of peginterferon and ribavirin with telaprevir or boceprevir is the standard treatment of hepatitis C virus (HCV) genotype 1 infection. However, these drugs are not well tolerated because of their side effects and suboptimal virologic responses. In a phase 2a, open-label study, we examined the safety and efficacy of an interferon-free, ribavirin-free regimen of direct-acting antivirals, comprising daclatasvir (an NS5A replication complex inhibitor), asunaprevir (an NS3 protease inhibitor), and BMS-791325 (a non-nucleoside NS5B inhibitor), in patients with chronic HCV infection. We analyzed data from 66 treatment-naive patients with HCV genotype 1 infection without cirrhosis who were assigned randomly to groups given daclatasvir (60 mg, once daily), asunaprevir (200 mg, twice daily), and BMS-791325 (75 or 150 mg, twice daily) for 12 or 24 weeks. The primary end point was an HCV-RNA level less than 25 IU/mL at 12 weeks after treatment (sustained virologic response at 12 weeks [SVR12]). In 64 patients, HCV-RNA levels were less than 25 IU/mL by week 4 of treatment (including 48 of 49 patients with HCV genotype 1a infection and 45 of 46 patients with the non-CC interleukin 28B genotype). Sixty-one patients (92%) achieved SVR12, based on a modified intention-to-treat analysis. Virologic responses were similar between 12 and 24 weeks of treatment. During the study, 2 patients experienced viral breakthrough and 1 patient relapsed. There were no grade 3-4 increases in levels of alanine or aspartate aminotransferases or bilirubin; there were no deaths or discontinuations resulting from serious adverse events or adverse events related to the treatment regimen. The most common adverse events were headache, asthenia, and gastrointestinal symptoms. In a phase 2a study, the all-oral, interferon-free, and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 was well tolerated and achieved high rates of SVR12 in patients with HCV genotype 1 infection. Further studies of this regimen are warranted. ClinicalTrials.gov, number NCT01455090.

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (Rbv) is associated with higher SVR rates in patients with HCV Genotype 1 (G1) infection due to improved early virologic response at week 4 and week 12

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (Rbv) is associated with higher SVR rates in patients with HCV Genotype 1 (G1) infection due to improved early virologic response at week 4 and week 12

Analysis of boceprevir resistance associated amino acid variants (RAVs) in two phase 3 boceprevir clinical studies

BackgroundWe investigated the frequency of RAVs among patients failing to achieve SVR in two clinical trials. We also investigated the impact of interferon responsiveness on RAVs and specific baseline RAVs relationship with boceprevir treatment failure. MethodsData are from 1020 patients enrolled into either SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving boceprevir or placebo. RAVs were analyzed via population-based sequence analysis of the NS3 protease gene (success rate of >90% at a virus level of ≥10,000IU/mL) ResultsThe high SVR rate in patients who received boceprevir resulted in a low rate of RAVs; 7% was detected at baseline in all patients, which rose to 15% after treatment. However, RAVs were detected in 53% of patients that failed to achieve SVR, which declined to 22.8% 6–14 months following cessation of boceprevir therapy. Baseline RAVs alone were not predictive of virologic outcome; poor interferon responsiveness was highly predictive of non-SVR. RAVs were more frequently detected in poor interferon responders. ConclusionsWe detected no association between the presence of baseline amino acid variants at boceprevir resistance-associated loci and outcome in the context of good IFN response.

Efficacy and safety of boceprevir plus peginterferon–ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis

We assessed the safety and efficacy of boceprevir (BOC) plus peginterferon-ribavirin (PR) in patients with HCV-G1 infection and advanced fibrosis/cirrhosis (Metavir F3/F4). In two randomized controlled studies of previously untreated and previous treatment failures, patients received a 4-week lead-in of PR followed by PR plus placebo for 44 weeks (PR48); PR plus BOC using response guided therapy (BOC/RGT); or PR plus BOC for 44 weeks (BOC/PR48). The trials enrolled 178 patients with F3/4. HCV RNA levels at week 4 and 8 were highly predictive of response. No patient with F3/4 in the PR48 arm with a <1 log(10) decline in HCV RNA at week 4 achieved SVR, whereas those randomized to BOC/RGT or BOC/PR48 had SVR rates of 11-33% (F3) and 10-14% (F4). In these latter groups, patients with high baseline viral load (>2 × 10(6)IU/ml) had an overall SVR rate of 6% (2/33). For patients with a ≥1 log(10) decline at week 4, SVR rates in the BOC/PR48 arm of SPRINT-2 and RESPOND-2, respectively, were 77% and 87% vs. 18% and 50% for PR48; SVR rates in early responders (undetectable HCV RNA at week 8) were 90-93% in the BOC/PR48 arm. Neutropenia and thrombocytopenia were more common in cirrhotics than non-cirrhotics. BOC improves SVR rates in patients with F3/4, and longer treatment duration provides the most benefit. With triple therapy, SVR rates are modest in F4 patients with a <1 log(10) decline at week 4, thus the 4-week PR lead-in aids in the assessment of early futility.

Treatment of HCV genotype 1-infection with PEG-IFNα-2b and ribavirin: high SVR rate in patients who are dually infected with either genotype 2 or 3

Treatment of HCV genotype 1-infection with PEG-IFNα-2b and ribavirin: high SVR rate in patients who are dually infected with either genotype 2 or 3

High SVR-Rates in Patients With HCV Genotype 1-Infection, Who Are Dually Infected With Either Genotype 2 or 3 and Treated With PEG-IFNα-2B and Ribavirin

High SVR-Rates in Patients With HCV Genotype 1-Infection, Who Are Dually Infected With Either Genotype 2 or 3 and Treated With PEG-IFNα-2B and Ribavirin

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G A A b st ra ct s therapy. Thus, 48 week-therapy had a tendency to increase the SVR rate in patients with late virological response (p=0.067). Two relapsers in super rapid virological response group showed genotype 2b and one of relapsers was obliged to receive reduced dose of ribavirin due to anemia. The therapy was discontinued in 6.1% (4/65) of the subjects due to depression, nausea, fatigue, or ileus. There were no significant differences of the severity and incidence of side effect due to the therapy among 12-week therapy group, 24-week therapy group and 48-week therapy group. Conclusions: The SVR rate for 12-week therapy in super rapid virological response group was comparable to the overall SVR rate for the standard 24-week therapy in patients with genotype 2 and a high viral road. The 48 week-therapy had a tendency to increase the SVR rate in late virological response group and showed the safety comparable to the standard 24-week therapy. Response-guided therapy based on week 2 and 4 after peginterferon alfa-2b plus ribavirin therapy was very useful for optimizing the therapy duration.

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G A A b st ra ct s therapy. Thus, 48 week-therapy had a tendency to increase the SVR rate in patients with late virological response (p=0.067). Two relapsers in super rapid virological response group showed genotype 2b and one of relapsers was obliged to receive reduced dose of ribavirin due to anemia. The therapy was discontinued in 6.1% (4/65) of the subjects due to depression, nausea, fatigue, or ileus. There were no significant differences of the severity and incidence of side effect due to the therapy among 12-week therapy group, 24-week therapy group and 48-week therapy group. Conclusions: The SVR rate for 12-week therapy in super rapid virological response group was comparable to the overall SVR rate for the standard 24-week therapy in patients with genotype 2 and a high viral road. The 48 week-therapy had a tendency to increase the SVR rate in late virological response group and showed the safety comparable to the standard 24-week therapy. Response-guided therapy based on week 2 and 4 after peginterferon alfa-2b plus ribavirin therapy was very useful for optimizing the therapy duration.

Interferon monotherapy of chronic hepatitis C in dialysis patients: meta‐analysis of clinical trials

The efficacy of monotherapy with interferon (IFN) (conventional or pegylated IFN) in dialysis patients with chronic hepatitis C remains unclear, although a number of clinical trials have been published addressing this issue. The aim of the study was to evaluate the efficacy and safety of monotherapy by conventional or pegylated IFN in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR; as a measure of efficacy), and the secondary outcome was drop-out rate (as a measure of tolerability). We used the random-effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 28 clinical trials (645 unique patients), of which six (21.4%) had a controlled design. In the group of trials based on conventional IFN, the summary estimate for SVR and drop-out rate was 39% [95% confidence interval (CI) 32-46] and 19% (95% CI 13-26) respectively. The summary estimate for SVR rate in patients with the hepatitis C virus genotype 1 was 33% (95% CI 19-47). In the subset of trials using pegylated IFN, the summary estimate for SVR and drop-out rate was 31% (95% CI 7-55) and 27% (95% CI 1-52) respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms, and gastrointestinal and haematological changes. A relationship between age and drop-out rate was found, even if no statistical significance was reached (P = 0.064). The studies were heterogeneous with regard to SVR and drop-out rate. No publication bias was observed. One-third of dialysis patients with chronic hepatitis C were successfully treated with conventional or pegylated IFN monotherapy. Preliminary evidence does not support additional benefit due to monotherapy with pegylated IFN on the viral response in the chronic kidney disease (CKD) population. Tolerance to IFN monotherapy was unsatisfactory, particularly to pegylated IFN. The optimal antiviral treatment of chronic hepatitis C in dialysis populations is currently under active investigation.