The Experts below are selected from a list of 1926 Experts worldwide ranked by ideXlab platform
Gaetano Filice - One of the best experts on this subject based on the ideXlab platform.
-
Area-under-the-curve for Peginterferon Alpha-2a and Peginterferon Alpha-2b is not related to body weight in treatment-naive patients with chronic hepatitis C.
Antiviral therapy, 2005Co-Authors: Raffaele Bruno, Valentina Ciappina, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Cristina Zocchetti, Gaetano FiliceAbstract:One reason for dosing a drug by body weight is to reduce interpatient variability in clinical response. This study evaluated the relationship between body weight and drug exposure for Peginterferon Alpha-2a and Peginterferon Alpha-2b used in combination with ribavirin for treating patients with chronic hepatitis C. These two products are dosed differently: Peginterferon Alpha-2a is flat-dosed at 180 μg regardless of body weight, whereas Peginterferon Alpha-2b is dosed by body weight at 0.5-1.5 μg/kg. Body-weight dosing of Peginterferon Alpha-2b is purported to overcome the adverse effect of increased body weight on sustained virological response. To test this hypothesis, we measured the area-under-the-curve (AUC) for both drugs as part of a previously reported pharmacokinetics study. In total, 22 interferon-naive patients with chronic hepatitis C were treated for 12 weeks. Patients were randomly assigned in a 1:1 ratio to receive once-weekly Peginterferon Alpha-2a 180 μg (n=10) or Peginterferon Alpha-2b 1.0 μg/kg (n=12). Ribavirin was dosed by body weight at 1000 mg/day (≤75 kg) or 1200 mg/day (>75 kg). We found no correlation between body weight and AUC for either Peginterferon Alpha-2a or Peginterferon Alpha-2b. Considerable interpatient variability in AUC occurred for Peginterferon Alpha-2a [coefficient of variation (CV): 37.5%] and, despite dosing by body weight, for Peginterferon Alpha-2b (CV: 36.8%). Thus, there appears to be no rationale for a body-weight dosing regimen for Peginterferon Alpha-2a, and such dosing does not achieve more consistent AUC measurements in patients receiving Peginterferon Alpha-2b.
-
Viral dynamics and pharmacokinetics of Peginterferon Alpha-2a and Peginterferon Alpha-2b in naive patients with chronic hepatitis c: a randomized, controlled study.
Antiviral Therapy, 2004Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano FiliceAbstract:The two available pegylated interferon formulations, Peginterferon Alpha-2a and Peginterferon Alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving Peginterferon Alpha-2b either once or twice weekly suggests that once-weekly administration of Peginterferon Alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between Peginterferon Alpha-2a and Peginterferon Alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive Peginterferon Alpha2a 180 µg (n=10) or Peginterferon Alpha-2b 1.0 µg/kg (n=12) once weekly. Serum Peginterferon concentrations were measured at baseline, 24, 48, 120 and 168 h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon Alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received Peginterferon Alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, Peginterferon Alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the Peginterferon Alpha-2a group versus the Peginterferon Alpha-2b group (2.8126 vs 3.8726; P
-
viral dynamics and pharmacokinetics of Peginterferon Alpha 2a and Peginterferon Alpha 2b in naive patients with chronic hepatitis c a randomized controlled study
Antiviral Therapy, 2004Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano FiliceAbstract:The two available pegylated interferon formulations, Peginterferon Alpha-2a and Peginterferon Alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving Peginterferon Alpha-2b either once or twice weekly suggests that once-weekly administration of Peginterferon Alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between Peginterferon Alpha-2a and Peginterferon Alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive Peginterferon Alpha-2a 180 microg (n=10) or Peginterferon Alpha-2b 1.0 microg/kg (n=12) once weekly. Serum Peginterferon concentrations were measured at baseline, 24, 48, 120 and 168h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon Alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received Peginterferon Alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, Peginterferon Alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the Peginterferon Alpha-2a group versus the Peginterferon Alpha-2b group (2.8126 vs 3.8726; P<0.01). The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs. In conclusion, once-weekly administration of Peginterferon Alpha-2b (1.0 microg/kg/wk) may be insufficient for continuous interferon exposure; twice-weekly administration may help avoid increases in viral replication as interferon levels decline. Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations.
Peter Ferenci - One of the best experts on this subject based on the ideXlab platform.
-
dauphine a randomized phase ii study of danoprevir ritonavir plus Peginterferon Alpha 2a ribavirin in hcv genotypes 1 or 4
Liver International, 2015Co-Authors: Gregory T. Everson, Curtis Cooper, Peter Ferenci, Pietro Andreone, Mitchell L Shiffman, Christophe Hézode, Eric M. Yoshida, Savino Bruno, Teresita Beltranjaramillo, Stefan ZeuzemAbstract:Background & Aims Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus Peginterferon Alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection. Methods Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA <15 IU/ml during Weeks 2–10) stopped all therapy at Week 12; non-eRVR2 patients continued all treatment to Week 24. The primary efficacy endpoint was sustained the virological response (SVR24: HCV RNA <15 IU/ml after 24 weeks of untreated follow-up). Results SVR24 rates in Arms A, B, C, D and E were 89.1%, 78.5%, 66.0%, 69.1% and 36.4%, respectively, in the overall population; 83.6%, 69.6%, 60.3%, 59.2% and 38.5% in G1a-infected patients, 96.6%, 93.1%, 73.1%, 78.4% and 28.6% in G1b-infected patients and 100%, 87.5%, 100%, 100% and 66.7% in G4-infected patients. Danoprevir/r plus P/R was generally well tolerated compared with P/R alone. There was a higher incidence of serious adverse events in danoprevir-treatment arms, but most were associated with P/R. Conclusions The combination of danoprevir/r plus P/R is efficacious in treatment-naive patients with HCV genotype 1 or 4 infection.
-
DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus Peginterferon Alpha-2a/ribavirin in HCV genotypes 1 or 4.
Liver international : official journal of the International Association for the Study of the Liver, 2014Co-Authors: Gregory T. Everson, Curtis Cooper, Peter Ferenci, Pietro Andreone, Mitchell L Shiffman, Christophe Hézode, Eric M. Yoshida, Teresita Beltran-jaramillo, Savino Bruno, Stefan ZeuzemAbstract:Background & Aims Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus Peginterferon Alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection. Methods Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA
-
twice weekly administration of Peginterferon Alpha 2b improves viral kinetics in patients with chronic hepatitis c genotype 1
Journal of Viral Hepatitis, 2003Co-Authors: Elisabeth Formann, Wolfgang Jessner, L. Bennett, Peter FerenciAbstract:The decline in hepatitis C viral load on treatment with Peginterferon-Alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of Peginterferon-Alpha-2b may improve viral kinetics. Ten interferon-naive patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg Peginterferon-Alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of Peginterferon-Alpha-2b were measured. Peginterferon-Alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, Peginterferon-Alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) Peginterferon-Alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of Peginterferon-Alpha-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, Peginterferon-Alpha-2b has to be given at least two times weekly.
-
Twice-weekly administration of Peginterferon-Alpha-2b improves viral kinetics in patients with chronic hepatitis C genotype 1.
Journal of viral hepatitis, 2003Co-Authors: Elisabeth Formann, Wolfgang Jessner, L. Bennett, Peter FerenciAbstract:The decline in hepatitis C viral load on treatment with Peginterferon-Alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of Peginterferon-Alpha-2b may improve viral kinetics. Ten interferon-naive patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg Peginterferon-Alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of Peginterferon-Alpha-2b were measured. Peginterferon-Alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, Peginterferon-Alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) Peginterferon-Alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and
Stefan Zeuzem - One of the best experts on this subject based on the ideXlab platform.
-
dauphine a randomized phase ii study of danoprevir ritonavir plus Peginterferon Alpha 2a ribavirin in hcv genotypes 1 or 4
Liver International, 2015Co-Authors: Gregory T. Everson, Curtis Cooper, Peter Ferenci, Pietro Andreone, Mitchell L Shiffman, Christophe Hézode, Eric M. Yoshida, Savino Bruno, Teresita Beltranjaramillo, Stefan ZeuzemAbstract:Background & Aims Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus Peginterferon Alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection. Methods Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA <15 IU/ml during Weeks 2–10) stopped all therapy at Week 12; non-eRVR2 patients continued all treatment to Week 24. The primary efficacy endpoint was sustained the virological response (SVR24: HCV RNA <15 IU/ml after 24 weeks of untreated follow-up). Results SVR24 rates in Arms A, B, C, D and E were 89.1%, 78.5%, 66.0%, 69.1% and 36.4%, respectively, in the overall population; 83.6%, 69.6%, 60.3%, 59.2% and 38.5% in G1a-infected patients, 96.6%, 93.1%, 73.1%, 78.4% and 28.6% in G1b-infected patients and 100%, 87.5%, 100%, 100% and 66.7% in G4-infected patients. Danoprevir/r plus P/R was generally well tolerated compared with P/R alone. There was a higher incidence of serious adverse events in danoprevir-treatment arms, but most were associated with P/R. Conclusions The combination of danoprevir/r plus P/R is efficacious in treatment-naive patients with HCV genotype 1 or 4 infection.
-
DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus Peginterferon Alpha-2a/ribavirin in HCV genotypes 1 or 4.
Liver international : official journal of the International Association for the Study of the Liver, 2014Co-Authors: Gregory T. Everson, Curtis Cooper, Peter Ferenci, Pietro Andreone, Mitchell L Shiffman, Christophe Hézode, Eric M. Yoshida, Teresita Beltran-jaramillo, Savino Bruno, Stefan ZeuzemAbstract:Background & Aims Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus Peginterferon Alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection. Methods Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA
-
clinical trial individualized treatment duration for hepatitis c virus genotype 1 with Peginterferon Alpha 2a plus ribavirin
Alimentary Pharmacology & Therapeutics, 2008Co-Authors: Kwok H. Tang, Stefan Zeuzem, Eva Herrmann, I. Pachiadakis, Emma Paulon, N. Tatman, Nikolai V. NaoumovAbstract:Summary Background Individualized treatment regimens, taking into account the heterogeneity of patients with chronic hepatitis C, are needed to improve treatment outcomes. Aim To investigate prospectively the period of undetectable viraemia required for a high rate of sustained virological response in patients with chronic hepatitis C genotype 1 and the relationship to early viral kinetics. Methods Forty-five chronic hepatitis C genotype 1 patients were given Peginterferon-Alpha 2a plus ribavirin. Viraemia and hepatocyte HCV-RNA levels were quantified using a TaqMan assay. Beyond the first time point of undetectable viraemia (<20 IU/mL) between baseline and treatment week 12, 32 of 45 (71%) patients were randomized to additional 12 weeks (G12); 24 weeks (G24) or 36 weeks therapy (G36). The remaining 13 patients received 48 weeks’ treatment (G48). Results The sustained virological response rates were: G12 – five of 11 (45%); G24 – eight of 10 (80%); G36 – eight of 11 (73%); G48 – four of 13 (31%). The anti-viral efficacy (e) and treatment-induced loss of infected hepatocytes (Mδ), were significantly higher in patients with early viral clearance. In G12, patients with sustained virological response had lower baseline viraemia than those who relapsed. Conclusions Early viraemia clearance is a better marker than baseline viral load and differentiates chronic hepatitis C genotype 1 with high or low probability of sustained virological response. In patients with viraemia clearance within 12 weeks of starting peg-interferon/ribavirin therapy, an additional period of undetectable viraemia of minimum 24 weeks is required for high sustained virological response.
-
comparing the safety tolerability and quality of life in patients with chronic hepatitis b vs chronic hepatitis c treated with Peginterferon Alpha 2a
Liver International, 2008Co-Authors: Patrick Marcellin, Teerha Piratvisuth, Rajender K Reddy, George K K Lau, Stefan Zeuzem, Jenny E Heathcote, Paul J Pockros, Patrizia Farci, Wan Cheng Chow, Jidong JiaAbstract:Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of Peginterferon Alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg Peginterferon Alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of Peginterferon Alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression.
-
Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with Peginterferon Alpha-2a.
Liver international : official journal of the International Association for the Study of the Liver, 2008Co-Authors: Patrick Marcellin, Teerha Piratvisuth, K. Rajender Reddy, E. Jenny Heathcote, George K K Lau, Stefan Zeuzem, Paul J Pockros, Patrizia Farci, Wan Cheng Chow, Jidong JiaAbstract:Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of Peginterferon Alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg Peginterferon Alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P
Christian Gluud - One of the best experts on this subject based on the ideXlab platform.
-
Peginterferon Alpha 2a versus Peginterferon Alpha 2b for chronic hepatitis c
Cochrane Database of Systematic Reviews, 2014Co-Authors: Goran Hauser, Tahany Awad, Kristian Thorlund, Davor Stimac, Mahasani Mabrouk, Christian GluudAbstract:Abstract BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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 ; I2 = 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 ; I2= 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. AUTHORS' CONCLUSIONS: 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.
-
The Cochrane Library - Peginterferon Alpha‐2a versus Peginterferon Alpha‐2b for chronic hepatitis C
The Cochrane database of systematic reviews, 2014Co-Authors: Goran Hauser, Tahany Awad, Kristian Thorlund, Davor Stimac, Mahasani Mabrouk, Christian GluudAbstract:Abstract BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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 ; I2 = 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 ; I2= 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. AUTHORS' CONCLUSIONS: 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.
-
"Real-Life" Comparison of Pegylated-Interferon 2a Versus 2b Combination Therapy of Chronic Hepatitis C Virus Reply
Hepatology, 2011Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Mabrouk, Christian GluudAbstract:A combination of weekly pegylated interferon (Peginterferon) Alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (Peginterferon Alpha-2a or Peginterferon alfa-2b) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5, 008 patients, that compared Peginterferon Alpha-2a plus ribavirin versus Peginterferon alfa-26 plus ribavirin. Overall, Peginterferon Alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus Peginterferon alfa-26 (47% versus 41% ; risk ratio 1.11, 95% confidence interval 1.04-1.19 ; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two Peginterferons. Conclusion: Current evidence suggests that Peginterferon Alpha-2a is associated with higher SVR than Peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one Peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010 ; 51:1176-1184.)
-
Proceed with Caution Peginterferon Alpha-2a versus Peginterferon Alfa-2b in Chronic Hepatitis C. A Systematic Review of Randomized Trials Reply
Hepatology, 2010Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Marbrouk, Christian GluudAbstract:A combination of weekly pegylated interferon (Peginterferon) Alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (Peginterferon Alpha-2a or Peginterferon alfa-2b) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5, 008 patients, that compared Peginterferon Alpha-2a plus ribavirin versus Peginterferon alfa-26 plus ribavirin. Overall, Peginterferon Alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus Peginterferon alfa-26 (47% versus 41% ; risk ratio 1.11, 95% confidence interval 1.04-1.19 ; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two Peginterferons. Conclusion: Current evidence suggests that Peginterferon Alpha-2a is associated with higher SVR than Peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one Peginterferon over the other, because any potential benefit must outweigh the risk of harm.
-
Peginterferon Alpha-2a is associated with higher sustained virological response than Peginterferon alfa-2b in chronic hepatitis C: Systematic review of randomized trials†‡
Hepatology (Baltimore Md.), 2009Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Mabrouk, Christian GluudAbstract:A combination of weekly pegylated interferon (Peginterferon) Alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (Peginterferon Alpha-2a or Peginterferon alfa-2b) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared Peginterferon Alpha-2a plus ribavirin versus Peginterferon alfa-2b plus ribavirin. Overall, Peginterferon Alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus Peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04–1.19; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two Peginterferons. Conclusion: Current evidence suggests that Peginterferon Alpha-2a is associated with higher SVR than Peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one Peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010.)
Raffaele Bruno - One of the best experts on this subject based on the ideXlab platform.
-
Area-under-the-curve for Peginterferon Alpha-2a and Peginterferon Alpha-2b is not related to body weight in treatment-naive patients with chronic hepatitis C.
Antiviral therapy, 2005Co-Authors: Raffaele Bruno, Valentina Ciappina, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Cristina Zocchetti, Gaetano FiliceAbstract:One reason for dosing a drug by body weight is to reduce interpatient variability in clinical response. This study evaluated the relationship between body weight and drug exposure for Peginterferon Alpha-2a and Peginterferon Alpha-2b used in combination with ribavirin for treating patients with chronic hepatitis C. These two products are dosed differently: Peginterferon Alpha-2a is flat-dosed at 180 μg regardless of body weight, whereas Peginterferon Alpha-2b is dosed by body weight at 0.5-1.5 μg/kg. Body-weight dosing of Peginterferon Alpha-2b is purported to overcome the adverse effect of increased body weight on sustained virological response. To test this hypothesis, we measured the area-under-the-curve (AUC) for both drugs as part of a previously reported pharmacokinetics study. In total, 22 interferon-naive patients with chronic hepatitis C were treated for 12 weeks. Patients were randomly assigned in a 1:1 ratio to receive once-weekly Peginterferon Alpha-2a 180 μg (n=10) or Peginterferon Alpha-2b 1.0 μg/kg (n=12). Ribavirin was dosed by body weight at 1000 mg/day (≤75 kg) or 1200 mg/day (>75 kg). We found no correlation between body weight and AUC for either Peginterferon Alpha-2a or Peginterferon Alpha-2b. Considerable interpatient variability in AUC occurred for Peginterferon Alpha-2a [coefficient of variation (CV): 37.5%] and, despite dosing by body weight, for Peginterferon Alpha-2b (CV: 36.8%). Thus, there appears to be no rationale for a body-weight dosing regimen for Peginterferon Alpha-2a, and such dosing does not achieve more consistent AUC measurements in patients receiving Peginterferon Alpha-2b.
-
Viral dynamics and pharmacokinetics of Peginterferon Alpha-2a and Peginterferon Alpha-2b in naive patients with chronic hepatitis c: a randomized, controlled study.
Antiviral Therapy, 2004Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano FiliceAbstract:The two available pegylated interferon formulations, Peginterferon Alpha-2a and Peginterferon Alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving Peginterferon Alpha-2b either once or twice weekly suggests that once-weekly administration of Peginterferon Alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between Peginterferon Alpha-2a and Peginterferon Alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive Peginterferon Alpha2a 180 µg (n=10) or Peginterferon Alpha-2b 1.0 µg/kg (n=12) once weekly. Serum Peginterferon concentrations were measured at baseline, 24, 48, 120 and 168 h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon Alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received Peginterferon Alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, Peginterferon Alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the Peginterferon Alpha-2a group versus the Peginterferon Alpha-2b group (2.8126 vs 3.8726; P
-
viral dynamics and pharmacokinetics of Peginterferon Alpha 2a and Peginterferon Alpha 2b in naive patients with chronic hepatitis c a randomized controlled study
Antiviral Therapy, 2004Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano FiliceAbstract:The two available pegylated interferon formulations, Peginterferon Alpha-2a and Peginterferon Alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving Peginterferon Alpha-2b either once or twice weekly suggests that once-weekly administration of Peginterferon Alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between Peginterferon Alpha-2a and Peginterferon Alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive Peginterferon Alpha-2a 180 microg (n=10) or Peginterferon Alpha-2b 1.0 microg/kg (n=12) once weekly. Serum Peginterferon concentrations were measured at baseline, 24, 48, 120 and 168h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon Alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received Peginterferon Alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, Peginterferon Alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the Peginterferon Alpha-2a group versus the Peginterferon Alpha-2b group (2.8126 vs 3.8726; P<0.01). The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs. In conclusion, once-weekly administration of Peginterferon Alpha-2b (1.0 microg/kg/wk) may be insufficient for continuous interferon exposure; twice-weekly administration may help avoid increases in viral replication as interferon levels decline. Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations.