Dataset Information

Safety and efficacy of two-step peginterferon ?-2a treatment in patients of chronic hepatitis B with acute exacerbation.

ABSTRACT: The focus of this study was to evaluate the safety and efficacy of sequential peginterferon ?-2a (Pegasys) therapy for chronic hepatitis B with acute exacerbation [ALT > 10 × upper limit of normal (ULN), bilirubin <2.0 mg/dL]. Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007. Nineteen HBeAg-positive patients (Group 1) had received entecavir ?pretreatment ?(when ALT > 10 × ULN) plus Pegasys (180 ?g/kg/week, when ALT was 5-10 × ULN) for 24 weeks. Thirteen HBeAg-negative patients (Group 2) had the same protocol for 48 weeks. In both groups, entecavir was then discontinued 14 days after the initiation of Pegasys. The results were compared, respectively, to 35 HBeAg-positive patients (Group 3) and 24 HBeAg-negative patients (Group 4), all with ALT > 5 × ULN, under continual entecavir monotherapy. The ALT levels of patients in Group 1 and 2 who had received entecavir pretreatment for a duration of 19.63 ± 3.34 days were below four times of ULN following 4 weeks of Pegasys treatment. At week 96, the rates of sustained virological response were 69.2% (9/13) and 80% (8/10), and the relapse rates were 23.1% (3/13) and 11.2% (1/9) for HBeAg-positive and HBeAg-negative patients with two-step Pegasys treatment, respectively. The HBeAg seroconversion rates were 46.2% in Group 1, and 42.1% in Group 3; HBsAg loss rates were 15.4% (2/13) in Group 1, and 30% (3/10) in Group 2, whereas none achieved HBsAg loss with entecavir monotherapy (Group 3 and 4). The two-step Pegasys treatment offers an alternative, other than the nucleos(t)ides, for treating chronic hepatitis B with acute exacerbation and provides a safe, efficacious, short-term and finite strategy.

SUBMITTER: Chen CC

PROVIDER: S-EPMC3489065 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Safety and efficacy of two-step peginterferon α-2a treatment in patients of chronic hepatitis B with acute exacerbation.

Chen C-C CC Wang P-C PC Chang H-W HW Chen C-F CF

Journal of viral hepatitis 20110704 3

The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α-2a (Pegasys) therapy for chronic hepatitis B with acute exacerbation [ALT > 10 × upper limit of normal (ULN), bilirubin <2.0 mg/dL]. Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007. Nineteen HBeAg-positive patients (Group 1) had received entecavir pretreatment (when ALT > 10 × ULN) plus Pegasys (180 μg/kg/week, when ALT was 5-10 × ULN) for 24 week ...[more]

PMID: 22329370

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Project description:This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-?-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-?-2b) plus ribavirin.In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-?-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-?-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D)???8 and anxiety scores (HADS-A)???8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined.During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p?=?0.048; Group 2: p?=?0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p?<?0.001) and week 24 (p?<?0.001), and a poor virological response to treatment was associated with depression at week 24 (p?=?0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p?=?0.038).This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-?-2a plus ribavirin and those who underwent a regiment with PegIFN-?-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study.This clinical study has been registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

Project description:To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection.Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group?I?included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493).Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well.Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Project description:BackgroundThis Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients.MethodsPatients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12).ResultsPhase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies.ConclusionsThe majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted.Trial registrationNCT01323244 . (date of registration: March 24, 2011).

Dataset Information

Safety and efficacy of two-step peginterferon ?-2a treatment in patients of chronic hepatitis B with acute exacerbation.

Publications

Safety and efficacy of two-step peginterferon α-2a treatment in patients of chronic hepatitis B with acute exacerbation.

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