Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active chronic hepatitis: a pilot study.
ABSTRACT The efficacy and tolerability of Peg-Interferon alpha-2a (Peg-IFNalpha-2a) versus Peg-Interferon alpha-2b (Peg-IFNalpha-2b) were compared in a patient cohort with hepatitis C virus (HCV)-related active chronic hepatitis, unresponsive to previous antiviral treatment with standard IFN (6 MU three times/week) plus ribavirin (10.6 mg/kg/day) for a period of at least 3 months.
A total of 143 patients were enrolled and randomized into two treatment groups (A-B). Group A (71 patients) received one vial of Peg-IFNalpha-2a weekly (180 microg) subcutaneously whereas Group B (72 patients) received 1.5 microg/kg of Peg-IFNalpha-2b weekly subcutaneously. Interferon was combined with ribavirin (15 mg/kg/day) in both groups and all patients who demonstrated nondetectable HCV-RNA or a >or=2(log) reduction in viral load at week 12, were treated for 48 weeks, with a 24-week follow up.
Group A (10/71) and Group B (8/72) patients discontinued treatment due to severe side effects. At the end of therapy, HCV-RNA was undetectable in 17/71 (23.9%) Group A and in 19/72 (26.4%) of Group B patients. When terminating follow up, a sustained virological response was observed in 14/71 in Group A (19.7%) and 13/72 in Group B (18.0%).
Within the limits of the relatively small sample size, Peg-IFNalpha-2a and Peg-IFNalpha-2b demonstrated nonstatistically significant differences in effectiveness in patients nonresponsive to previous antiviral treatment.
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ABSTRACT: A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. However, it is not established which of the two licensed peginterferon products, peginterferon alpha-2a or peginterferon alpha-2b, is the most effective and has a better safety profile. To systematically evaluate the benefits and harms of peginterferon alpha-2a versus peginterferon alpha-2b in head-to-head randomised clinical trials in patients with chronic hepatitis C. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until October 2013. We also searched conference abstracts, journals, and grey literature. We included randomised clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b given with or without co-intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi-randomised studies and observational studies as identified by the searches were also considered for assessment of harms. Our primary outcomes were all-cause mortality, liver-related morbidity, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. The secondary outcome was sustained virological response in the blood serum. Two authors independently used a standardised data collection form. We meta-analysed data with both the fixed-effect and the random-effects models. For each outcome we calculated the relative risk (RR) with 95% confidence interval (CI) based on intention-to-treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risks of random errors (play of chance). Intervention effects on the outcomes were assessed according to GRADE. We included 17 randomised clinical trials which compared peginterferon alpha-2a plus ribavirin versus peginterferon alpha-2b plus ribavirin in 5847 patients. All trials had a high risk of bias. Very few trials reported data on very few patients for the patient-relevant outcomes all-cause mortality, liver-related morbidity, serious adverse events, and quality of life. Accordingly, we were unable to conduct meta-analyses on all-cause mortality, liver-related morbidity, and quality of life. Twelve trials reported on adverse events leading to discontinuation of treatment without clear evidence of a difference between the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI 0.57 to 1.22; I(2) = 44%; low quality evidence). A trial sequential analysis showed that we could exclude a relative risk reduction of 20% or more on this outcome. Peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response in the blood serum compared with peginterferon alpha-2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I(2)= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype, and treatment history yielded similar results. Trial sequential analyses supported the results in patients with genotypes 1 and 4, but not in patients with genotypes 2 and 3. There is lack of evidence on patient-important outcomes and paucity of evidence on adverse events. Moderate quality evidence suggests that peginterferon alpha-2a is associated with a higher sustained virological response in serum than with peginterferon alpha-2b. This finding may be affected by the high risk of bias of the included studies . The clinical consequences of peginterferon alpha-2a versus peginterferon alpha-2b are unknown, and we cannot translate an effect on sustained virological response into comparable clinical effects because sustained virological response is still an unvalidated surrogate outcome for patient-important outcomes. The lack of evidence on patient-important outcomes and the paucity of evidence on adverse events means that we are unable to draw any conclusions about the effects of one peginterferon over the other.Cochrane database of systematic reviews (Online) 02/2014; 2(2):CD005642. DOI:10.1002/14651858.CD005642.pub3
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ABSTRACT: The hepatitis C virus may lead to cirrhosis, liver cancer, liver transplant, and increased mortality. With standard treatment peginterferon-alpha and ribavirin (PR), sustained viral response (SVR) was less than 50 %. SVR rates improve greatly when PR is combined with telaprevir or boceprevir.Applied Health Economics and Health Policy 08/2014; DOI:10.1007/s40258-014-0120-y
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ABSTRACT: We aimed to compare the rates of sustained virologic response (SVR) achieved with peginterferon (PEG-IFN) alfa-2a and alfa-2b in combination with ribavinin (RBV) for chronic hepatitis C, using a large database of hepatitis cases to improve the generalizability of these results. We identified patients with chronic hepatitis C who were treated with PEG-IFN alfa-2a or alfa-2b and RBV, from the Japanese Interferon Database, between December 2009 and April 2013. This database contains the medical records of IFN treatment collected from 36 prefectures in Japan. Multivariable logistic regression analysis was used to compare SVR rates obtained with PEG-IFN alfa-2a and alfa-2b, in combination with RBV. A total of 16,349 patients were recorded in the Japanese Interferon Database. After application of the exclusion criteria, 12,706 patients (3,578 [1,710 males, 1,868 females] on PEG-IFN alfa-2a; and 9,128 [4,652 males, 4,476 females] on PEG-IFN alfa-2b) were included in this analysis. The SVR rate in the PEG-IFN alfa-2b group was 62.0%, as compared with a rate of 55.1% in the PEG-IFN alfa-2a group (crude odds ratio =1.31; 95% confidence interval [CI]: 1.23 to 1.44). There was no significant difference in the adjusted SVR rates between the two groups (adjusted odds ratio =0.96; 95% CI: 0.88 to 1.05). Similar proportions of adverse events were observed in the two groups, with the exception of thrombocytopenia, retinopathy, and anemia. There was no significant difference in the SVR rates and safety profile between chronic hepatitis C patients treated with the PEG-IFN alfa-2a and alfa-2b.Drug Design, Development and Therapy 01/2015; 9:283-90. DOI:10.2147/DDDT.S72245