Dataset Information

Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.

ABSTRACT: BACKGROUND & AIMS:The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. METHODS:Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 microg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. RESULTS:During the lead-in, >or=4-log(10) decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by >or=4 log(10) during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. CONCLUSIONS:Viral suppression by >or=4 log(10) with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

SUBMITTER: Shiffman ML

PROVIDER: S-EPMC3774149 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.

Shiffman Mitchell L ML Morishima Chihiro C Dienstag Jules L JL Lindsay Karen L KL Hoefs John C JC Lee William M WM Wright Elizabeth C EC Naishadham Deepa D Everson Gregory T GT Lok Anna S AS Di Bisceglie Adrian M AM Bonkovsky Herbert L HL Ghany Marc G MG

Gastroenterology 20090910 6

<h4>Background & aims</h4>The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated ...[more]

PMID: 19747918

Similar Datasets

Project description:Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device.In trial 1, 50 healthy adult subjects received one 180 ?g dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 ?g peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment.In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0-168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin.These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.

Dataset Information

Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.

Publications

Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets