Peginterferon

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Mitchell L. Shiffman - One of the best experts on this subject based on the ideXlab platform.

  • Peginterferon alfa 2b or alfa 2a with ribavirin for treatment of hepatitis c infection
    The New England Journal of Medicine, 2009
    Co-Authors: John G. Mchutchison, Eric Lawitz, Reem Ghalib, L. Nyberg, Andrew J. Muir, Mitchell L. Shiffman, Eugene R Schiff, Greg Galler, Jonathan Mccone, Joseph S Galati
    Abstract:

    Background Treatment guidelines recommend the use of Peginterferon alfa-2b or Peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: Peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or Peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the Peginterferon alfa-2b regimens and between the standard-dose Peginterferon alfa2b regimen and the Peginterferon alfa-2a regimen. Results Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose Peginterferon alfa-2b, 38.0% with low-dose Peginterferon alfa-2b, and 40.9% with Peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose Peginterferon alfa-2b; P = 0.57 for standard-dose Peginterferon alfa-2b vs. Peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peg interferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose Peginterferon alfa-2b and Peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose Peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose Peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for Peginterferon alfa2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available Peginterferon– ribavirin regimens or between the two doses of Peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.)

  • R1626 plus Peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin.
    Hepatology, 2008
    Co-Authors: Paul J Pockros, Maribel Rodriguez-torres, E. Godofsky, Reem Ghalib, Stephen A. Harrison, L. Nyberg, Michael W. Fried, Gregory T. Everson, David R. Nelson, Mitchell L. Shiffman
    Abstract:

    R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with Peginterferon alfa-2a ± ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + Peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + Peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + Peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (Peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (

  • r1626 plus Peginterferon alfa 2a provides potent suppression of hepatitis c virus rna and significant antiviral synergy in combination with ribavirin
    Hepatology, 2008
    Co-Authors: Paul J Pockros, E. Godofsky, Reem Ghalib, Stephen A. Harrison, L. Nyberg, Michael W. Fried, Gregory T. Everson, David R. Nelson, Maribel Rodrigueztorres, Mitchell L. Shiffman
    Abstract:

    R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with Peginterferon alfa-2a ± ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + Peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + Peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + Peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (Peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log10 IU/mL. Synergy was observed between R1626 and Peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions. Conclusion: A synergistic antiviral effect was observed when R1626 was combined with Peginterferon alfa-2a ± ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with Peginterferon alfa-2a and ribavirin is underway. (HEPATOLOGY 2008.)

  • Peginterferon alfa‐2a/ribavirin in hepatitis C virus patients nontolerant or nonresponsive to Peginterferon alfa‐2b/ribavirin
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: Vinod K Rustgi, Fayez M. Hamzeh, Susanna Esposito, Mitchell L. Shiffman
    Abstract:

    Summary Background  Peginterferon alfa-2a/ribavirin treatment resulted in fewer incidences of depression and flu-like symptoms than that of standard interferon/ribavirin, whereas Peginterferon alfa-2b/ribavirin and standard interferon/ribavirin treatment resulted in similar incidences of these adverse events (AEs). Aim  To assess the efficacy and safety of Peginterferon alfa-2a/ribavirin in genotype 1-infected patients treated for up to 12 weeks with Peginterferon alfa-2b/ribavirin but not achieving early virologic response (EVR) (non-EVR) or nontolerant (NT) because of depression, fatigue, flu-like symptoms, or injection-site reactions. Methods  Nontolerants were treated for an additional 36 weeks and non-EVRs for an additional 60 weeks with Peginterferon alfa-2a (180 μg/week)/ribavirin (1000/1200 mg/day). Patients with detectable HCV RNA after 12 weeks were discontinued. Results  Of 25 NTs, 23 (92%) were HCV-RNA negative after 12 weeks on Peginterferon alfa-2a/ribavirin and 14 (56%) achieved sustained virologic response. Of 32 non-EVRs to Peginterferon alfa-2b/ribavirin, four (13%) achieved EVR with Peginterferon alfa-2a/ribavirin and one (3%) achieved sustained virologic response. Four non-EVRs and 0 NTs were withdrawn for AEs; 26 (81%) and 24 (96%), respectively, completed Peginterferon alfa-2a/ribavirin treatment or were withdrawn for insufficient response at week 12. In NTs, depression, fatigue, flu-like symptoms, and injection-site reactions declined during treatment. Conclusion  Most patients who did not tolerate Peginterferon alfa-2b/ribavirin because of AEs, and who completed the full 36-week course of Peginterferon alfa-2a/ribavirin treatment, achieved sustained virologic response.

  • impact of reducing Peginterferon alfa 2a and ribavirin dose during retreatment in patients with chronic hepatitis c
    Gastroenterology, 2007
    Co-Authors: Mitchell L. Shiffman, Timothy R. Morgan, Gregory T. Everson, Marc G Ghany, Elizabeth C Wright, Karen L Lindsay, Anna S F Lok, Herbert L Bonkovsky, Adrian M Di Bisceglie, William M Lee
    Abstract:

    Background & Aims: Reducing the dose of Peginterferon and/or ribavirin to Methods: Nine hundred thirty-six patients with chronic hepatitis C genotype 1, advanced fibrosis, or cirrhosis (Ishak 3–6) and prior nonresponse to standard interferon ± ribavirin were retreated with Peginterferon alfa-2a (180 μg/wk) and ribavirin (1000–1200 mg/day) during the lead-in phase of the HALT-C trial. The percentage of each medication actually taken during treatment was calculated. Results: Reducing the total cumulative dose of Peginterferon received during the first 20 weeks of treatment from full dose (≥98%) to ≤60% reduced week 20 virologic response (W20 VR) from 35% to 12% and SVR from 17% to 5%. Reducing the dose of ribavirin from full dose (≥98%) to ≤60% did not affect either W20 VR or SVR as long as ribavirin dosing was not interrupted for more than 7 consecutive days. Prematurely discontinuing ribavirin, even at full-dose Peginterferon, reduced W20 VR to ≤19% and SVR to ≤4%. Conclusions: Reducing the Peginterferon dose during the first 20 weeks of treatment reduced viral clearance and SVR. In contrast, reducing ribavirin did not affect either W20 VR or SVR as long as patients remained on full-dose Peginterferon. Discontinuing ribavirin prematurely was associated with a marked decline in both VR and SVR.

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, 2014
    Co-Authors: Goran Hauser, Tahany Awad, Kristian Thorlund, Davor Stimac, Mahasani Mabrouk, Christian Gluud
    Abstract:

    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, 2014
    Co-Authors: Goran Hauser, Tahany Awad, Kristian Thorlund, Davor Stimac, Mahasani Mabrouk, Christian Gluud
    Abstract:

    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, 2011
    Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Mabrouk, Christian Gluud
    Abstract:

    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, 2010
    Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Marbrouk, Christian Gluud
    Abstract:

    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.), 2009
    Co-Authors: Tahany Awad, Goran Hauser, Kristian Thorlund, Davor Stimac, Mahasen Mabrouk, Christian Gluud
    Abstract:

    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.)

Patrick Marcellin - One of the best experts on this subject based on the ideXlab platform.

  • Predicting early and sustained virological responses in prior nonresponders to pegylated interferon alpha-2b plus ribavirin retreated with Peginterferon alpha-2a plus ribavirin and the benefit-risk ratio of retreatment.
    Journal of clinical gastroenterology, 2013
    Co-Authors: Patrick Marcellin, Antonio Craxì, K. Rajender Reddy, Adrian M Di Bisceglie, B. Freilich, Pietro Andreone, Carlos E. Brandao-mello, Antonio Olveira Martin, G. Teuber, Diethelm Messinger
    Abstract:

    GOALS To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with Peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to Peginterferon alpha-2b (12 kDa). BACKGROUND In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of Peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to Peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA

  • Peginterferon, Ribavirin and Anti-viral Triple Therapy
    Chronic Hepatitis C Virus, 2011
    Co-Authors: Patrick Marcellin, Nathalie Boyer, Tarik Asselah
    Abstract:

    Several clinical trials have now demonstrated that when patients with chronic HCV genotype 1 are treated with the combination of a protease inhibitor, Peginterferon and ribavirin SVR is significantly greater compared to treatment with Peginterferon and ribavirin. In treatment naive patients SVR is increased from approximately 45% to 69–75%. The duration of treatment can be shortened in approximately 60% of the patients. In experienced patients SVR rates are approximately 50%. Two protease inhibitors, telaprevir and boceprevir, have now completed phase 3 clinical trials and should be approved by regulatory bodies in many countries during 2011. These two medications are associated with adverse events over and above those observed with Peginterferon and ribavirin including worsening anemia, rash and dysgusia. Numerous other protease and polymerase inhibitors are currently being evaluated in phase 3 clinical trials. The combination of multiple direct acting anti-viral agents along with peginteferon and ribavirin may allow treatment to be shortened in many patients while still achieving high rates of SVR in the future.

  • telaprevir for previously untreated chronic hepatitis c virus infection
    The New England Journal of Medicine, 2011
    Co-Authors: Ira M Jacobson, Peter Ferenci, John G. Mchutchison, Andrew J. Muir, Rajender K Reddy, Patrick Marcellin, Adrian M Di Bisceglie, Geoffrey Dusheiko, Natalie Bzowej, Robert Flisiak
    Abstract:

    A B S T R AC T Background In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with Peginterferon–ribavirin, as compared with Peginterferon–ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. Methods In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with Peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by Peginterferon–ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with Peginterferon–ribavirin for 8 weeks and placebo with Peginterferon–ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of Peginterferon–ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with Peginterferon–ribavirin for 12 weeks, followed by 36 weeks of Peginterferon–ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Results Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving Peginterferon–ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Conclusions Telaprevir with Peginterferon–ribavirin, as compared with Peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.)

  • Telaprevir Is Effective Given Every 8 or 12 Hours With Ribavirin and Peginterferon Alfa-2a or -2b to Patients With Chronic Hepatitis C
    Gastroenterology, 2010
    Co-Authors: Patrick Marcellin, Giampiero Carosi, Peter Ferenci, Tobias Goeser, Lawrence Serfaty, Koen De Backer, Joost P H Drenth, Frederik Nevens, Xavier Forns, Rolf Van Heeswijk
    Abstract:

    Background & Aims Recent studies have shown that 12 weeks of treatment with telaprevir, administered every 8 hours (q8h), combined with pegylated interferon (Peginterferon) alfa-2a plus ribavirin significantly increased the rate of hepatitis C virus (HCV) eradication (sustained virologic response [SVR]) in patients infected with HCV genotype 1 compared with approved therapy. We investigated the efficacy, safety, tolerability, and pharmacokinetics of telaprevir given q8h or every 12 hours (q12h) in combination with Peginterferon alfa-2a or alfa-2b. Methods Treatment-naive patients (n = 161) infected with HCV genotype 1 were randomly assigned to groups that were given open-label telaprevir (750 mg q8h or 1125 mg q12h) in combination with standard doses of Peginterferon alfa-2a (180 μg/wk) and ribavirin (1000–1200 mg/day) or Peginterferon alfa-2b (1.5 μg·kg −1 ·wk −1 ) and ribavirin (800–1200 mg/day). Patients received triple therapy for 12 weeks, followed by 12 or 36 additional weeks of treatment with Peginterferon alfa and ribavirin, based on virologic response. Results Baseline characteristics were similar for all groups. SVR rates were 81.0% to 85.0% among groups; most patients received 24 weeks of therapy (68.0%). There were no significant differences in SVR rates (intent-to-treat analysis) among groups ( P ≥ .787), between the pooled q8h and q12h groups ( P = .997), or between the pooled Peginterferon alfa-2a/ribavirin and Peginterferon alfa-2b/ribavirin groups ( P = .906). The safety profile was similar among all groups. Conclusions A high proportion (>80%) of patients achieved an SVR regardless of the telaprevir dosing frequency (q8h or q12h) or type of Peginterferon alfa used (alfa-2a or alfa-2b).

  • sustained response of hepatitis b e antigen negative patients 3 years after treatment with Peginterferon alfa 2a
    Gastroenterology, 2009
    Co-Authors: Patrick Marcellin, Patrizia Farci, Cihan Yurdaydin, Selim Gurel, Zhimeng Lu, Ferruccio Bonino, Teerha Piratvisuth, M Popescu, Jian Wu, Stephanos J Hadziyannis
    Abstract:

    Background & Aims Patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B treated with Peginterferon alfa-2a with or without lamivudine achieve significantly higher 6-month posttreatment rates of response compared with those treated with lamivudine alone. The durability of ≤3-year posttreatment response was investigated in this study. Methods Patients received Peginterferon alfa-2a only (180 μg once weekly; n=177), in combination with lamivudine (100 mg daily; n=179) or lamivudine alone (n = 181) for 48 weeks. A total of 315 patients (116, 114, and 85, respectively) participated in this posttreatment observational study. Results Three years after treatment, the percentage of patients with normal alanine aminotransferase (ATL) was higher for patients treated with Peginterferon alfa-2a (31%) than with lamivudine (18%; P = 0.032). Similarly, 28% of patients treated with Peginterferon had hepatitis B virus (HBV) DNA levels ≤ 10,000 copies/mL versus 15% of patients treated with lamivudine ( P = .039). Peginterferon alfa-2a treatment and high baseline ALT level were independent baseline predictors of long-term virologic response ( P = .040 and P = .01, respectively). Of the patients who had been treated with a Peginterferon alfa-2a–containing regimen, 8.7% cleared hepatitis B surface antigen (HBsAg; 44% of those with undetectable HBV at 3-year posttreatment follow-up) compared with none treated with lamivudine alone. Conclusions Biochemical and virologic responses were sustained for ≤3 years in approximately 25% of patients given a 48-week course of Peginterferon alfa-2a, with or without lamivudine. The increased rate of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B supports the use of Peginterferon alfa-2a as a first-line treatment.

Gaetano Filice - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of Peginterferon pharmacokinetic and pharmacodynamic profiles
    Journal of Viral Hepatitis, 2012
    Co-Authors: Raffaele Bruno, Paolo Sacchi, Laura Maiocchi, Gaetano Filice, Serena Cima, Stefano Novati, Stefano Fagiuoli
    Abstract:

    Summary.  The pharmacokinetics and in dosing regimens of the currently available pegylated interferon (Peginterferon) alfa molecules differ greatly, depending on the size and nature of their polyethylene glycol (PEG) moiety. Peginterferon alfa-2a has a branched 40 kDa PEG chain covalently attached to lysine residues and circulates as an intact molecule. On the other hand, Peginterferon alfa-2b has a linear 12 kDa PEG chain covalently attached to interferon-a-2b via an unstable urethane bond that is hydrolysed after injection, releasing native interferon alfa-2b. The difference in pegylation between the two Peginterferons has a significant impact on their pharmacokinetic properties. Data from comparative and non-comparative studies indicate that Peginterferon alfa-2b has a shorter half-life in serum than Peginterferon alfa-2a, and a significant proportion of patients receiving Peginterferon alfa-2b may have trough concentrations below the limit of detection during the latter part of the 7-day dosing schedule. However, the pharmacodynamic parameters of the two drugs appear to be similar.

  • Pharmacodynamics of Peginterferon alfa‐2a and Peginterferon alfa‐2b in interferon‐naïve patients with chronic hepatitis C: a randomized, controlled study
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: Raffaele Bruno, Paolo Sacchi, Carolina Scagnolari, Laura Maiocchi, S.f.a. Patruno, Francesca Bellomi, Gaetano Filice, Francesca Torriani, Guido Antonelli
    Abstract:

    Summary Background  Peginterferon alfa-2a and alfa-2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. Aim  To compare the pharmacodynamics of Peginterferon alfa-2a and Peginterferon alfa-2b in interferon-naive patients with chronic hepatitis C. Methods  Patients were randomized to receive Peginterferon alfa-2a, 180 μg (n = 10) or Peginterferon alfa-2b 1.0 μg/kg (n = 12) once weekly. The enzymatic activity of 2′5′-oligoadenylate synthetase and levels of neopterin and β2-microglobulin were measured at baseline and at 24, 48, 120 and 168 h. Results  Oligoadenylate synthetase activity and serum neopterin and β2-microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration-time curve of either Peginterferon and the area under the concentration-time curve for 2′,5′-oligoadenylate synthetase, neopterin and β2-microglobulin. The area under the concentration-time curves calculated for these three markers did not correlate with body mass index stratified at

  • 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, 2005
    Co-Authors: Raffaele Bruno, Valentina Ciappina, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Cristina Zocchetti, Gaetano Filice
    Abstract:

    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, 2004
    Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano Filice
    Abstract:

    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, 2004
    Co-Authors: Raffaele Bruno, Valentina Ciappina, Cristina Zochetti, Paolo Sacchi, Laura Maiocchi, S.f.a. Patruno, Gaetano Filice
    Abstract:

    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.

John G. Mchutchison - One of the best experts on this subject based on the ideXlab platform.

  • telaprevir for previously untreated chronic hepatitis c virus infection
    The New England Journal of Medicine, 2011
    Co-Authors: Ira M Jacobson, Peter Ferenci, John G. Mchutchison, Andrew J. Muir, Rajender K Reddy, Patrick Marcellin, Adrian M Di Bisceglie, Geoffrey Dusheiko, Natalie Bzowej, Robert Flisiak
    Abstract:

    A B S T R AC T Background In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with Peginterferon–ribavirin, as compared with Peginterferon–ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. Methods In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with Peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by Peginterferon–ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with Peginterferon–ribavirin for 8 weeks and placebo with Peginterferon–ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of Peginterferon–ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with Peginterferon–ribavirin for 12 weeks, followed by 36 weeks of Peginterferon–ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Results Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving Peginterferon–ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Conclusions Telaprevir with Peginterferon–ribavirin, as compared with Peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.)

  • telaprevir for previously treated chronic hcv infection
    The New England Journal of Medicine, 2010
    Co-Authors: John G. Mchutchison, Hendrik W. Reesink, Andrew J. Muir, Jenny E Heathcote, Michael P Manns, Norah A Terrault, Ira M Jacobson, Nezam H Afdhal, Stefan Zeuzem, Jyotsna Garg
    Abstract:

    Background Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with Peginterferon alfa and ribavirin have a low likelihood of success with retreatment. Methods We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after Peginterferon alfa–ribavirin therapy to one of four treatment groups: 115 patients to the T12PR24 group, receiving telaprevir (1125-mg loading dose, then 750 mg every 8 hours) for 12 weeks and Peginterferon alfa-2a (180 μg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 24 weeks; 113 patients to the T24PR48 group, receiving telaprevir for 24 weeks and Peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group); 111 patients to the T24P24 group, receiving telaprevir and Peginterferon alfa-2a for 24 weeks (at the same doses as in the T12PR24 group); and 114 patients to the PR48 (or control) group, receiving Peginterferon alfa-2a and ribaviri...

  • Peginterferon alfa 2b or alfa 2a with ribavirin for treatment of hepatitis c infection
    The New England Journal of Medicine, 2009
    Co-Authors: John G. Mchutchison, Eric Lawitz, Reem Ghalib, L. Nyberg, Andrew J. Muir, Mitchell L. Shiffman, Eugene R Schiff, Greg Galler, Jonathan Mccone, Joseph S Galati
    Abstract:

    Background Treatment guidelines recommend the use of Peginterferon alfa-2b or Peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: Peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or Peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the Peginterferon alfa-2b regimens and between the standard-dose Peginterferon alfa2b regimen and the Peginterferon alfa-2a regimen. Results Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose Peginterferon alfa-2b, 38.0% with low-dose Peginterferon alfa-2b, and 40.9% with Peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose Peginterferon alfa-2b; P = 0.57 for standard-dose Peginterferon alfa-2b vs. Peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peg interferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose Peginterferon alfa-2b and Peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose Peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose Peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for Peginterferon alfa2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available Peginterferon– ribavirin regimens or between the two doses of Peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.)

  • Antiviral effects and safety of telaprevir, Peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients
    Journal of Hepatology, 2008
    Co-Authors: Eric Lawitz, Lindsay Mcnair, Tara L. Kieffer, Maribel Rodriguez-torres, Ariya Khunvichai, Andrew J. Muir, John G. Mchutchison
    Abstract:

    Background/Aims This study assessed the safety and antiviral effects of telaprevir (VX-950) in combination with Peginterferon alfa-2a and ribavirin. Methods Twelve treatment-nai¨ve patients with chronic genotype 1 hepatitis C virus infection received telaprevir (750mg q8h), Peginterferon alfa-2a (180μg/week), and ribavirin (1000 or 1200mg/day) for 28 days. Patients could then start off-study treatment with Peginterferon alfa-2a and ribavirin for up to 44 weeks, at the discretion of the investigator and patient. Results The combination of telaprevir, Peginterferon alfa-2a, and ribavirin was well tolerated, with no serious adverse events or treatment discontinuations. Rash or pruritus occurred in 5 of the 12 patients; all cases resolved either during or after the end of telaprevir treatment. All 12 patients had undetectable HCV RNA levels by day 28 (rapid viral response, RVR). Eight patients completed 44 weeks of off-study Peginterferon alfa-2a and ribavirin treatment. Eight patients achieved a sustained viral response (SVR), including one patient who received only 22 weeks of treatment. Conclusions The combination of telaprevir, Peginterferon alfa-2a, and ribavirin was generally well tolerated. Events of pruritus and rash resolved during or after end of telaprevir dosing. All 12 patients achieved an RVR.

  • cost effectiveness of Peginterferon α 2b plus ribavirin versus interferon α 2b plus ribavirin for initial treatment of chronic hepatitis c
    Gut, 2003
    Co-Authors: John G. Mchutchison, Michael P Manns, Uwe Siebert, G Sroczynski, S Rossol, Jurgen Wasem, U Ravenssieberer, B M Kurth, John B Wong
    Abstract:

    Background: Peginterferon α-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. Aims: To estimate the cost effectiveness of treatment with Peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. Methods: Individual patient level data from a randomised clinical trial with Peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. Results: Compared with no antiviral therapy, Peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon α-2b plus ribavirin, Peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of €11 800 and €6600 per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that Peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. Conclusions: Peginterferon α-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.

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