Optimal Dosing Frequency of Pegylated Interferon Alfa-2b Monotherapy for Chronic Hepatitis C Virus Infection

Size: px
Start display at page:

Download "Optimal Dosing Frequency of Pegylated Interferon Alfa-2b Monotherapy for Chronic Hepatitis C Virus Infection"

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3: Optimal Dosing Frequency of Pegylated Interferon Alfa-2b Monotherapy for Chronic Hepatitis C Virus Infection YOAV LURIE,* REGINE ROUZIER PANIS, GEORGE J. M. WEBSTER, GEOFFREY M. DUSHEIKO, MARK LAUGHLIN, MARY L. JACKSON, and RAN OREN* *Tel Aviv Medical Center, Tel Aviv, Israel; Centre CAP, Montpellier, France; Centre for Hepatology, Royal Free Campus, Royal Free University College School of Medicine, London, United Kingdom; and Schering-Plough Research Institute, Kenilworth, New Jersey Background & Aims: Pegylated interferon alfa-2b (PEG- IFN-alfa 2b ) has been shown to provide superior efficacy to IFN-alfa 2b in patients with chronic hepatitis C (predominantly genotype 1) infection as measured by viral clearance. This study was conducted to determine the optimal dosing regimen of PEG-IFN-alfa 2b required to obtain a maximum decrease of hepatitis C viral RNA. Methods: This was a 24-week, open-label, multicenter, parallel-group, randomized, active-controlled trial in the United Kingdom, France, and Israel. Individuals (n 61) with chronic hepatitis C infection, genotype 1, received IFN-alfa 2b 3 miu 3 times weekly for 24 weeks, or PEG- IFN-alfa 2b 1.5 or 3.0 g/kg/wk, as total weekly full or split doses, for 12 weeks. At week 12, serum RNA titer was measured, and all PEG-IFN-alfa 2b patients continued with /wk for a further 12 weeks. Results: Mean serum hepatitis C RNA levels decreased in all groups at weeks 12 and 24. PEG-IFN-alfa 2b 1.5 g/ kg/wk was superior to IFN-alfa 2b in decreasing mean serum hepatitis C RNA (P <.05 at week 12). The efficacy of split-dose PEG-IFN-alfa 2b 1.5 or 3.0 g/ kg/wk regimens was not significantly different from full-dose PEG-IFN-alfa 2b /wk. However, there was a significant decrease in neutrophil count in groups receiving PEG-IFN-alfa 2b 3.0 g/kg/wk or lower, multiple-dose per week regimens. Conclusions: PEG-IFNalfa 2b once weekly is the optimal dosing frequency for patients with chronic hepatitis C with predominantly genotype 1 infection. More frequent dosing or increasing the dose to 3.0 g/kg/wk did not result in improved antiviral effects, but did decrease neutrophil counts. The development of pegylated interferon alfa-2b (PEG-IFN-alfa 2b ) (PEG-INTRON; Schering Corporation, Kenilworth, NJ) significantly has improved the management of hepatitis C virus (HCV) infections. The half-life of PEG-IFN-alfa 2b is longer and the clearance is lower than those of interferon-alfa 2 (IFN-alfa 2 ), allowing once-weekly dosing as opposed to the 3 injections per week required with IFN-alfa 2. Moreover, PEG-IFN-alfa 2b provides greater drug exposure than that achieved with IFN-alfa 2, 1 and has proven to be significantly more efficacious in decreasing viral load. 2 When used in combination with ribavirin, PEG-IFN-alfa 2b evokes a sustained response in significantly more patients than does monotherapy, with studies reporting a 54% 3 and 56% 4 rate of drug response. Consequently, PEG-IFN-alfa 2 in combination with ribavirin is the standard treatment for patients with HCV infection. 2 The superior clinical efficacy of PEG-IFN-alfa 2b in combination with ribavirin over IFN-alfa 2 has been established firmly, with the optimal dosing schedule of PEG-IFN-alfa 2b being /wk in combination with ribavirin or 1.0 g/kg/wk when used as monotherapy, both as recommended by the Food and Drug Administration. 5,6 However, a point of controversy has been raised in the literature, questioning the approved once-weekly weight-based dosing regimen of PEG-IFN-alfa 2b vs. the use of a twice-weekly dosing regimen. 7 This phase I/II trial of PEG-IFN-alfa 2b was conducted to determine the optimal frequency of dosing and the therapeutic value of weight-based PEG-IFNalfa 2b administration in individuals with chronic HCV genotype 1 infection, as measured by viral response and safety. This study sought to determine whether dividing the PEG-IFN-alfa 2b /wk dose into a 2- or 3-times/wk dose would lead to improved antiviral effect or safety compared with a once-weekly dose. In addition, clinical findings have shown that the effect of PEG-IFN-alfa 2b in viral clearance is dose dependent. 8 The study therefore also tested PEG-IFNalfa 2b 3.0 g/kg/wk as a single or split dose to determine whether a higher weekly, weight-adjusted dose would yield a better response. Abbreviations used in this paper: AE, adverse event; PEG-IFN, pegylated interferon by the American Gastroenterological Association /05/$30.00 PII: /S (04)

2 June 2005 PEGYLATED INTERFERON ALFA-2b DOSING FREQUENCY 611 Table 1. Treatment Groups Drug Dose Times weekly Total/wk IFN-alfa 2b (control) 3 MIU 3 9 MIU PEG-IFN-alfa 2b 1 PEG-IFN-alfa 2b.75 g/kg 2 PEG-IFN-alfa 2b.5 g/kg 3 PEG-IFN-alfa 2b g/kg PEG-IFN-alfa 2b 1.0 g/kg g/kg Materials and Methods Study Design This was a phase I/II, open-label, multicenter, parallelgroup, randomized, active-controlled trial performed at 3 clinical centers in the United Kingdom, France, and Israel. Each center s institutional review board approved the study, and written informed consent was obtained from each individual. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki, as reflected in a priori approval by each institution s Human Research Committee. The randomized treatment phase lasted 12 weeks. To be eligible, individuals needed to have chronic HCV genotype 1 infection with an RNA titer of copies/ml, an increased alanine transaminase concentration at the time of enrollment, and to have undergone a liver biopsy examination showing chronic HCV without cirrhosis in the 12 months before the study. Individuals were excluded if they had undergone prior IFN treatment, had human immunodeficiency virus infection or autoimmune disease, or consumed 20 g/day of alcohol. Participants were assigned randomly to 1 of 6 treatment groups (Table 1). Five groups received varied doses of PEG- IFN-alfa 2b (PEG-INTRON; Schering Corporation) 1, 2, or 3 times per week. The sixth group was the control group, treated with standard IFN-alfa 2b (INTRON A; Schering Corporation). Local laboratories performed the standard biochemical and hematologic assays, and a centralized laboratory performed the HCV-RNA and HCV genotype determinations. Blood samples for laboratory safety evaluation were obtained at screening, on the day before the first dose of the drug was administered, weekly for 4 weeks (weeks 1 4), and then every 2 weeks until week 12 (weeks 6 12). Blood samples for determining serum HCV-RNA concentrations were obtained using the same schedule. Serum HCV-RNA assays were performed by a quantitative reverse-transcription polymerase chain-reaction assay with a detection limit of 100 copies/ml (National Genetics Institute, Culver City, CA). 9 Study End Points Primary end point. This study determined the antiviral effect of treatment at week 12 as changes in HCV-RNA titer, the percentage of patients with a decrease of at least 2 log 10 in serum HCV-RNA concentration, and PEG-IFN-alfa 2b safety at week 12. Secondary end point. The percentage of patients with a decrease of at least 2 log 10 in serum HCV-RNA concentration at week 24 also was determined. Safety Evaluation Safety was monitored using clinical and laboratory data and patient-reported adverse events (AEs). AEs reported during treatment were graded as mild, moderate, severe, or lifethreatening using the modified World Health Organization guidelines. 10 Study medications were discontinued if certain threshold laboratory values were exceeded, as defined in the trial protocol. Study medications were discontinued in patients with any life-threatening AEs. Statistical Analyses Patients were randomized centrally to 1 of 6 treatment groups. The study was designed to have 10 patients in each treatment group to achieve an 89% chance of detecting any untoward event with a true incidence rate of 20%. The chance of detection is 80% if the true incidence is 15%. Safety analyses were based on data from all randomized patients; in the case of patient dropout, the last observation was carried forward. Serum HCV-RNA concentration data were based on data from all treated patients. Differences and changes in HCV-RNA concentrations were evaluated using the Fisher exact test. Results Subject Characteristics and Disposition A total of 61 patients were randomized to receive PEG-IFN-alfa 2b or IFN-alfa 2b. Patient demographics and baseline disease characteristics, including age, sex, and baseline viral load, were similar across treatment groups (Table 2). All patients, with the exception of 2 patients receiving PEG-IFN-alfa 2b 1.0 g/kg 3 times per week, completed at least 12 weeks of therapy. A total of 55 patients (90%) completed 24 weeks of treatment. Decrease in Serum Hepatitis C Virus RNA Titers at Week 12 At the end of 12 weeks of treatment, all groups showed a mean decrease in serum HCV-RNA concentration, with the greatest decrease being in patients receiving PEG-IFN-alfa 2b once weekly. Figure 1 shows the relative mean decreases in log 10 HCV-RNA titer from baseline. All 6 treatment groups showed a mean decrease in HCV-RNA levels of at least 1 log 10. The 5 groups receiving PEG-IFN-alfa 2b experienced a greater decrease in HCV-RNA level than the IFN-alfa 2b group. Because of the limited power of the study for the end point of HCV-RNA clearance, only the groups with the greatest decrease in viral titer the patients who received PEG-IFN-alfa 2b once a week or 1.0

3 612 LURIE ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 6 Table 2. Subject Demographics at Baseline IFN-alfa 2b PEG-IFN-alfa 2b 3 MIU 1 time/wk.75 g/kg.5 g/kg 1.0 g/kg Patients, n Mean age (y) Age range (y) Gender, n (%) Male 6 (60) 5 (50) 5 (50) 5 (50) 5 (45) 5 (50) Female 4 (40) 5 (50) 5 (50) 5 (50) 6 (55) 5 (50) Race, n (%) Caucasian 10 (100) 9 (90) 10 (100) 10 (100) 10 (91) 10 (100) African American 0 (0) 1 (10) 0 (0) 0 (0) 1 (9) 0 (0) HCV genotype 1, n (%) 10 (100) 10 (100) 10 (100) 10 (100) 10 (91) 10 (100) Mean baseline viral load, 10 6 copies/ml NOTE. Differences across treatment groups were not statistically significant. g/kg 3 times per week showed a significantly greater decrease than the IFN-alfa 2b group (P.05). There were no statistically significant differences in mean log 10 HCV-RNA level decrease between the 5 PEG-IFN-alfa 2b groups. In addition, there was no apparent trend toward greater decreases in the 2 groups receiving PEG-IFNalfa 2b 3.0 g/kg/wk than in the 3 groups receiving PEG-IFN-alfa 2b /wk. Percentage of Patients With 2 Log 10 or Greater Decrease in Hepatitis C Virus RNA at Week 12 The percentage of patients in each group who experienced at leasta2log 10 decrease in HCV-RNA titer is shown in Table 3. This percentage was at least 2-fold greater in all 5 PEG-IFN-alfa 2b groups than in the IFN-alfa 2b group. For example, 20% of patients in the IFN-alfa 2b group achieved a decrease in viral clearance of at least 2 log 10, compared with 70% of patients in the Figure 1. Effect of PEG-IFN-alfa 2b dosage on HCV-RNA clearance at week 12. Bars are mean values with standard error (*P.05 vs IFN-alfa 2b ). BIW, ; QW, 1 time/wk; TIW,. PEG-IFN-alfa 2b once-weekly group. Because of the small size of the study, this difference was not statistically significant. There was no evidence of any trend toward greater improvement in HCV-RNA clearance for the 2 groups receiving PEG-IFN-alfa 2b 3.0 g/kg/wk compared with the 3 groups receiving PEG- IFN-alfa 2b /wk. Percentage of Hepatitis C Virus RNA Negative Patients at Week 24 All treated patients switched to PEG-IFN-alfa 2b once a week at week 12. At week 24, virologic response rates remained higher with PEG-IFN-alfa 2b therapy than with IFN-alfa 2b therapy. All dosages of PEG-IFN-alfa 2b were superior to IFN-alfa 2b in decreasing HCV-RNA concentration, as determined by reversetranscription polymerase chain reaction. Overall, 5 of 10 (50%) patients treated with PEG-IFN-alfa 2b once a week for 24 weeks were HCV-RNA negative, compared with 0 of 10 (0%) patients treated with IFNalfa 2b. Proportions of HCV-RNA negative patients, as determined by reverse-transcription polymerase chain reaction at week 24 in the PEG-IFN-alfa 2b.75 and 1.5 g/kg twice-weekly groups, were 6 of 10 (60%) and 3 of 11 (27%), respectively. Proportions of HCV-RNA negative patients in the PEG-IFN-alfa 2b.5 and 1.0 g/kg 3-times weekly groups were 4 of 10 (40%) and 3 of 10 (30%), respectively. Virologic response was higher numerically in the PEG-IFN-alfa 2b groups who received a total dose of /wk (40% 60%) than in the groups who received a total dose of 3.0 g/kg/wk (30%). At week 24, the virologic response rates in the PEG- IFN-alfa 2b 1.5- and 3.0- g/kg/wk groups were significantly greater than those in the IFN-alfa 2b group (P.014 and.0136, respectively).

4 June 2005 PEGYLATED INTERFERON ALFA-2b DOSING FREQUENCY 613 Table 3. Effect of PEG-IFN-alfa 2b Dosage on HCV-RNA Decrease IFN-alfa 2b PEG-IFN-alfa 2b 3 MIU 1 time/wk.75 g/kg.5 g/kg 1.0 g/kg Patients, n log 10 decrease in HCV RNA (%) HCV RNA negative at week HCV RNA negative at week Safety PEG-IFN-alfa 2b /wk (in either once weekly or divided doses) was well tolerated, with a safety profile similar to that of IFN-alfa 2b. Adverse events with PEG-IFN-alfa 2b and IFN-alfa 2b generally were mild or moderate in severity and were not treatment-limiting. There were no life-threatening AEs or deaths reported in this study. The higher dose of PEG-IFN-alfa 2b (3.0 g/kg/wk) was not as well tolerated as either the recommended dose of PEG-IFN-alfa 2b (/wk) or IFN-alfa 2b.AEs reported for PEG-IFN-alfa 2b 3.0 g/kg/wk included fatigue, headache, weight loss, and nausea. Injection-site reactions were significantly more frequent with PEG- IFN-alfa 2b 3.0 g/kg/wk than with PEG-IFN-alfa 2b 1.5 g/kg/wk (33% vs 7%), and were not reported at all with IFN-alfa 2b. Flu-like symptoms were common in all study groups. The incidences of psychiatric AEs were consistent across groups receiving PEG-IFN-alfa 2b (20% in each group), with the exception of those receiving 3.0 g/kg/wk (36%). Table 4 shows the most frequent AEs reported for patients receiving PEG-IFN-alfa 2b 1.5 and 3.0 g/kg/ wk. In the second 12 weeks of the study, all PEG-IFN groups received PEG-IFN once weekly, and the types and incidences of AEs during this period were similar. However, patients who received PEG-IFN-alfa 2b 3.0 g/kg/wk during the first 12 weeks of the study reported a greater incidence of weight loss and alopecia at the end of study than those who received PEG-IFN-alfa 2b /wk throughout the study. Six patients discontinued the study; however, only 2 discontinued before week 12. Three patients discontinued because of an AE; all received PEG-IFN-alfa 2b 3.0 g/kg/wk. One patient discontinued treatment at week 4 because of increases in alanine and aspartate transaminase levels above baseline values (205 and 150 U/L, respectively), 1 patient discontinued treatment at week 10 because of epistaxis and petechiae, and 1 patient discontinued treatment at week 20 because of anemia (hemoglobin level, 8.90 g/dl). The remaining 3 patients discontinued because of noncompliance, failure to meet protocol eligibility, and relocation. Mean platelet counts decreased in all groups during the first 12 weeks of treatment. Platelet counts then rebounded during the second 12 weeks of treatment, except in patients treated with PEG-IFN-alfa 2b 1.5 g/ kg/wk, who showed a nonsignificant further decrease in platelet count during the second 12 weeks. Mean platelet counts returned to near-baseline levels at follow-up evaluation at week 6. Similarly, mean leukocyte and neutrophil counts decreased during treatment in all groups and returned to Table 4. Most Frequently Reported Adverse Events at Week 12 of PEG-IFN-alfa 2b Treatment 1 time/wk.75 g/kg.5 g/kg 1.0 g/kg Patients, n Adverse events, n (%) Asthenia 0 (0) 0 (0) 2 (20) 2 (18) 5 (50) Fatigue 0 (0) 1 (10) 2 (20) 2 (18) 1 (10) Flu-like symptoms 5 (50) 4 (40) 5 (50) 4 (36) 4 (40) Headache 1 (10) 0 (0) 1 (10) 4 (36) 2 (20) Nausea 0 (0) 1 (10) 2 (20) 5 (45) 1 (10) Psychiatric 2 (20) 2 (20) 2 (20) 4 (36) 2 (20) Weight loss 0 (0) 0 (0) 1 (10) 5 (45) 1 (10)

5 614 LURIE ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 6 Figure 2. Decrease in absolute neutrophil count (10 9 cells/l) by dose regimen, from treatment initiation through week 12. BIW, ; QW, 1 time/wk; TIW,. near-baseline counts at follow-up evaluation at week 6. Overall, patients receiving higher doses or 3 doses per week of PEG-IFN-alfa 2b showed greater decreases in absolute neutrophil count than those receiving PEG- IFN-alfa 2b once weekly. Decreases in neutrophil count were greatest in patients receiving PEG-IFNalfa 2b 3.0 g/kg/wk (1.0 g/kg or ) and in patients treated with PEG-IFN-alfa 2b 0.5 g/kg 3 times per week (Figure 2). Discussion This dose-ranging study was conducted to determine the optimal dose of PEG-IFN-alfa 2b and the relative safety and efficacy of this agent when administered 1, 2, or 3 times per week. The study predated both the 2001 Food and Drug Administration s approval of PEG- IFN-alfa plus ribavirin, and the 2002 National Institutes of Health s guidelines recommending combination therapy with ribavirin; PEG-IFN-alfa 2b therefore was evaluated as a monotherapy. This study also sought to determine whether the once a week dosage would be safer or more effective if administered as.75 g/kg twice a week or as.5 g/kg 3 times a week. The results at week 12 showed no significant difference in antiviral effect or safety between these split doses and the 1.5 g/kg once-weekly dose. These results provided justification for the pivotal combination therapy trial of PEG- IFN-alfa 2b and ribavirin, 3 and provide further support for the current recommendation of the onceweekly dose of PEG-IFN-alfa 2b. The degree of antiviral activity achieved with the once-weekly, weight-based dosing of PEG-IFN-alfa 2b monotherapy reported here indicates the overall efficacy and safety of PEG-IFN-alfa 2b in treatment of chronic HCV. Results show that PEG-IFN-alfa 2b once weekly was the most effective regimen for decrease of viral load with a manageable side-effect profile. The more recent findings of Manns et al. 3 extend these results, showing that the combination therapy of PEG-IFNalfa 2b plus ribavirin is more efficacious than IFN-alfa 2b plus ribavirin. Because clinical findings published before this investigation showed that the effect of IFN-alfa 2b in viral clearance is dose-dependent, 8 PEG-IFN-alfa 2b 3.0 g/ kg/wk also was studied to determine whether a higher dose would yield a better response. The 3.0- g/kg/wk dose of PEG-IFN-alfa 2b showed similar results to that of the 1.5- g/kg/wk dose with regard to antiviral effect. However, the higher dose was less tolerable to patients, even when administered in smaller doses 2 or 3 times per week. This suggests that the 1.5- g/kg/wk dose of PEG- IFN-alfa 2b might be approaching the upper weekly dosage limit, and supports the treatment recommendation of this PEG-IFN-alfa 2b dose for the treatment of therapynaive patients with HCV infection. This study showed that PEG-IFN-alfa 2b once weekly yields the greatest viral load decrease vs. IFN-alfa 2b, and that more frequent or higher-dose administration of PEG-IFN-alfa 2b did not improve this response. These results suggest that pharmacokinetics may be less important than pharmacodynamic parameters, and that the antiviral response of IFN is complicated and may have effects on multiple systems in the body. The prolonged kinetics of PEG-IFN-alfa 2b vs. IFN- increase the molecule s ability to activate and maintain global antiviral responses, which can have a pronounced effect on decrease of viral load. This phenomenon also has been shown for other biologics. 11,12 Overall, PEG-IFN-alfa 2b therapy showed a safety profile similar to that with IFN-alfa 2b treatment. However, all IFN therapy can be associated with a decrease in white blood cell, neutrophil, and platelet counts. These results suggest that neutrophil counts may be affected more negatively by multiple doses of PEG-IFN-alfa 2b each week than by once-weekly dosing. Patients who received either high-dose or 3-times-weekly dosing of PEG-IFNalfa 2b showed greater decreases from baseline in neutrophil count, suggesting that sustained exposure to IFNs may suppress bone marrow function; once-weekly dosing, which has a defined bell-shaped concentration time profile, may allow for bone marrow recovery and production of neutrophils. A recently published report supported the validity of these findings and provided evidence regarding early drug response in the treatment of HCV. Davis et al 13 have reported that the 12-week time frame represents a crucial threshold in HCV treatment. Most patients who were able to complete the first 12 weeks of therapy with PEG-IFN-alfa 2b combination therapy with ribavirin (REBETOL; Schering Corporation) and achieve a mea-

6 June 2005 PEGYLATED INTERFERON ALFA-2b DOSING FREQUENCY 615 sure of early viral response (69% 76% of patients) had a high probability of a sustained virologic response (67% 80%). Moreover, patients who did not show a clinical response after 12 weeks did not respond to an additional 9 months of therapy. At week 12, the current study found that 70% of HCV genotype 1 patients who received PEG-IFN-alfa 2b /wk showed an early viral response (defined as a 2 log 10 decrease in HCV- RNA level) compared with 20% of patients receiving IFN-alfa 2b. Phase III clinical trials of PEG-IFN-alfa 2b have shown that the weight-based dosing scheme of PEG-IFN-alfa 2b (/wk) was significantly more effective than the flat dosing scheme of IFN-alfa 2b (3 miu ), 14 and that there is durability of the response. The relevance of body weight, adherence to dosing, and viral response has been analyzed in 2 studies by McHutchison et al. 15,16 In the first study, heavier patients were found to respond less favorably than leaner patients to flat-dosed IFNalfa 2b, providing evidence that weight-based dosing increases efficacy rates. 15 A second retrospective analysis evaluated the impact of adherence to a combination therapy of PEG-IFN-alfa 2b plus ribavirin. The results indicated that individuals who maintain 80% of their PEG-IFN-alfa 2b and ribavirin dosage for the duration of treatment (24 48 wk) enhance their likelihood of achieving a sustained virologic response. 16 Taken together, successful therapy for chronic HCV infection requires compliant, weight-based dosing, which can be achieved with a once-weekly treatment regimen. In summary, the results of this study suggest that the optimal dose of PEG-IFN-alfa 2b for individuals with HCV infection is once weekly, and that there is no additional benefit in administering PEG-IFN-alfa 2b in a split-dose regimen. This once-weekly PEG-IFNalfa 2b treatment regimen provides a significant decrease in viral load with a safety profile similar to that of IFN-alfa, without a significant effect on immunologic supportive cells, such as neutrophils. References 1. Luxon BA, Grace M, Brassard D, et al. Pegylated interferons for the treatment of chronic hepatitis C infection. Clin Ther 2002;24: NIH Consensus Development Panel. Management of hepatitis C: 2002; June 10 12, NIH consensus statement. Available at: Accessed March 3, Manns MP, McHutchison JG, Gordon SC, et al, and the International Hepatitis Interventional Therapy Group. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358: Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347: Prescribing information: PEG-Intron (peginterferon alfa-2b) powder for injection. Physicians desk reference. 58th ed. Montvale, NJ: Thomson PDR, 2004: Food and Drug Administration Antiviral Drugs Advisory Committee. Briefing information: an update on the approval of BLA /5002, PEG-Intron (peginterferon alfa-2b) Powder for Injection, indicated for use alone or in combination with Rebetol (ribavirin, USP) for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and are at least 18 years of age. Available at: dockets/ac/01/briefing/3819b1.htm. Accessed March 3, Ferenci P. Weight-based dosing of pegylated interferon-alpha in chronic hepatitis C. Just a marketing gag? Dig Liver Dis 2003; 35: Lam NP, Neumann AU, Gretch DR, et al. Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa. Hepatology 1997;26: Tong MJ, Blatt LM, McHutchison JG, et al. Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison. Hepatology 1997;26: Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer 1981;47: Esposito P, Barbero L, Caccia P, et al. PEGylation of growth hormone-releasing hormone (GRF) analogues. Adv Drug Deliv Rev 2003;55: Green MD, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003;14: Davis GL, Wong JB, McHutchison JG, et al. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003;38: Lindsay KL, Trepo C, Heintges T, et al, for the Hepatitis Interventional Therapy Group. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 2001;34: McHutchison JG, Poynard T, Patel K, et al. Patient body weight and response to interferon alfa-2b monotherapy [abstract 998]. Hepatology 2001;34:P421A. 16. McHutchison JG, Manns M, Patel K, et al, for the International Hepatitis Interventional Therapy Group. Adherence to combination therapy enhances sustained response in genotype-1 infected patients with chronic hepatitis C. Gastroenterology 2002;123: Address requests for reprints to: Yoav Lurie, MD, Head, Hepatitis Clinic, Liver Unit, Department of Gastroenterology and Hepatology, 6 Weizmann Street, Tel Aviv 64239, Israel. danayoavlurie@ bezeqint.net; fax: (972) Supported by Schering-Plough Research Institute. Drs Laughlin and Jackson are employees of Schering-Plough Research Institute.

Current therapy for hepatitis C: pegylated interferon and ribavirin

Current therapy for hepatitis C: pegylated interferon and ribavirin Clin Liver Dis 7 (2003) 149 161 Current therapy for hepatitis C: pegylated interferon and ribavirin John G. McHutchison, MD a, Michael W. Fried, MD b, * a Duke Clinical Research Institute, Duke University

More information

Pegylated interferons (peginterferons) represent the

Pegylated interferons (peginterferons) represent the Viral Kinetics in Genotype 1 Chronic Hepatitis C Patients During Therapy With 2 Different Doses of Peginterferon Alfa-2b Plus Ribavirin Maria Buti, 1 Francisco Sanchez-Avila, 1 Yoav Lurie, 2 Carlos Stalgis,

More information

Pegylated Interferon Alfa-2b (Peg-Intron) Plus Ribavirin (Rebetol)in the Treatment of Chronic Hepatitis C: A Local Experience

Pegylated Interferon Alfa-2b (Peg-Intron) Plus Ribavirin (Rebetol)in the Treatment of Chronic Hepatitis C: A Local Experience Pegylated Interferon Alfa-2b (Peg-Intron) Plus Ribavirin (Rebetol)in the Treatment of Chronic Hepatitis C: A Local Experience E L Seow, PH Robert Ding Island Hospital, Penang, Malaysia. Introduction Hepatitis

More information

Prospective Analysis of Patient Education Time and Administration Errors Associated with Administration of Pegasys versus Peg-Intron

Prospective Analysis of Patient Education Time and Administration Errors Associated with Administration of Pegasys versus Peg-Intron Prospective Analysis of Patient Education Time and Administration Errors Associated with Administration of Pegasys versus Peg-Intron David Finkelman, MD, MBA Janet McRea, LPN Reprint requests to: David

More information

ةي : لآا ةرقبلا ةروس

ةي : لآا ةرقبلا ةروس سورة البقرة: اآلية HCV RELAPSERS AND NONRESPONDERS: How to deal with them? BY Prof. Mohamed Sharaf-Eldin Prof. of Hepatology and Gastroenterology Tanta University Achieving SVR The ability to achieve a

More information

Over the past decade, the introduction of

Over the past decade, the introduction of MANAGEMENT OF CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS: CLINICAL EXPERIENCE WITH PEGYLATED INTERFERON α PLUS RIBAVIRIN Raymond T. Chung, MD* ABSTRACT Coinfection with hepatitis C virus (HCV) is common

More information

Anemia in the Treatment of Hepatitis C Virus Infection

Anemia in the Treatment of Hepatitis C Virus Infection SUPPLEMENT ARTICLE Anemia in the Treatment of Hepatitis C Virus Infection Mark S. Sulkowski Center for Viral Hepatitis, Johns Hopkins University, Baltimore, Maryland Hepatitis C virus (HCV) infection is

More information

The medical management of hepatitis C

The medical management of hepatitis C CLINICAL EXPERIENCE WITH PEGYLATED INTERFERON α-2a PLUS RIBAVIRIN FOR CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS INFECTED WITH HIV: THE APRICOT STUDY Douglas T. Dieterich, MD* ABSTRACT Currently,

More information

Infergen (interferon alfacon-1) with Ribavirin (Copegus, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths)

Infergen (interferon alfacon-1) with Ribavirin (Copegus, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths) Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.03.04 Subject: Infergen with Ribavirin Page: 1 of 8 Last Review Date: March 13, 2014 Infergen with Ribavirin

More information

Intron A Hepatitis B. Intron A (interferon alfa-2b) Description

Intron A Hepatitis B. Intron A (interferon alfa-2b) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.01 Subject: Intron A Hepatitis B Page: 1 of 7 Last Review Date: November 30, 2018 Intron A Hepatitis

More information

Infergen Monotherapy. Infergen (interferon alfacon-1) Description

Infergen Monotherapy. Infergen (interferon alfacon-1) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.03.03 Subject: Infergen Monotherapy Page: 1 of 7 Last Review Date: March 13, 2014 Infergen Monotherapy

More information

Intron A Hepatitis C. Intron A (interferon alfa-2b) Description

Intron A Hepatitis C. Intron A (interferon alfa-2b) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.05 Subject: Intron A Hepatitis C Page: 1 of 5 Last Review Date: November 30, 2018 Intron A Hepatitis

More information

The role of triple therapy with protease inhibitors in hepatitis C virus genotype 1na «ve patients

The role of triple therapy with protease inhibitors in hepatitis C virus genotype 1na «ve patients The role of triple therapy with protease inhibitors in hepatitis C virus genotype 1na «ve patients David R. Nelson Clinical and Translational Science Institute, University of Florida, FL, USA Liver International

More information

Oral combination therapy: future hepatitis C virus treatment? "Lancet Oct 30;376(9751): Oral combination therapy with a nucleoside

Oral combination therapy: future hepatitis C virus treatment? Lancet Oct 30;376(9751): Oral combination therapy with a nucleoside Author manuscript, published in "Journal of Hepatology 2011;55(4):933-5" DOI : 10.1016/j.jhep.2011.04.018 Oral combination therapy: future hepatitis C virus treatment? Commentary article on the following

More information

Topic: Sovaldi, sofosbuvir Date of Origin: March 14, Committee Approval Date: August 15, 2014 Next Review Date: March 2015

Topic: Sovaldi, sofosbuvir Date of Origin: March 14, Committee Approval Date: August 15, 2014 Next Review Date: March 2015 Medication Policy Manual Policy No: dru332 Topic: Sovaldi, sofosbuvir Date of Origin: March 14, 2014 Committee Approval Date: August 15, 2014 Next Review Date: March 2015 Effective Date: October 1, 2014

More information

Treatment Options in HCV Relapsers and Nonresponders. Raymond T. Chung, M.D.

Treatment Options in HCV Relapsers and Nonresponders. Raymond T. Chung, M.D. Session IV Treatment Options in HCV Relapsers and Nonresponders Raymond T. Chung, M.D. Director of Hepatology, Massachusetts General Hospital, Associate Professor of Medicine, Harvard Medical School, Boston,

More information

SYNOPSIS Final Clinical Study Report for Study AI444031

SYNOPSIS Final Clinical Study Report for Study AI444031 Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Name of Active Ingredient: () Individual Study Table Referring to the Dossier (For National Authority Use Only) SYNOPSIS for Study

More information

Safety of Treatment in Cirrhotics in the Era of New Antiviral Therapies for Hepatitis C Virus

Safety of Treatment in Cirrhotics in the Era of New Antiviral Therapies for Hepatitis C Virus Safety of Treatment in Cirrhotics in the Era of New Antiviral Therapies for Hepatitis C Virus JEFFREY NADELSON MD, ALAN EPSTEIN MD, THOMAS SEPE MD BOSTON UNIVERSITY SCHOOL OF MEDICINE ROGER WILLIAMS MEDICAL

More information

The treatment of choice for chronic hepatitis C is

The treatment of choice for chronic hepatitis C is Early Identification of HCV Genotype 1 Patients Responding to 24 Weeks Peginterferon -2a (40 kd)/ribavirin Therapy Donald M. Jensen, 1 Timothy R. Morgan, 2 Patrick Marcellin, 3 Paul J. Pockros, 4 K. Rajender

More information

TRANSPARENCY COMMITTEE

TRANSPARENCY COMMITTEE The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 10 December 2008 REBETOL 200 mg capsules Pack of 84 (CIP code: 351 971.9) Pack of 112 (CIP code: 373 277.8) Pack of

More information

Reviews/Evaluations. Chronic Hepatitis C. Introduction and Epidemiology. Natural Course of HCV. Recommendations for Treatment

Reviews/Evaluations. Chronic Hepatitis C. Introduction and Epidemiology. Natural Course of HCV. Recommendations for Treatment Reviews/Evaluations Chronic Hepatitis C Introduction and Epidemiology Hepatitis C virus (HCV) is one of the most common blood-borne infections and cause of chronic liver disease in the United States (1).

More information

Review Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3

Review Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3 Review Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3 Thomas Berg 1 * and Giampiero Carosi 2 Antiviral Therapy 13 Suppl 1:17 22 1 Charite Universitatsmedizin Berlin, Berlin, Germany

More information

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients 5/12/216 Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients Alexander Monto, MD Professor of Clinical Medicine University of California San Francisco San Francisco,

More information

Annals of Hepatology 2003; 2(3): July-September: Original Article

Annals of Hepatology 2003; 2(3): July-September: Original Article Annals of Hepatology 2003; 2(3): July-September: 135-139 Annals of Hepatology Original Article Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: Analysis of Mexican

More information

Hepatitis C virus (HCV) replicates at a rapid rate,

Hepatitis C virus (HCV) replicates at a rapid rate, Early Virologic Response to Treatment With Peginterferon Alfa-2b plus Ribavirin in Patients With Chronic Hepatitis C Gary L. Davis, 1 John B. Wong, 2 John G. McHutchison, 3 Michael P. Manns, 4 Joann Harvey,

More information

TRANSPARENCY COMMITTEE OPINION. 10 December 2008

TRANSPARENCY COMMITTEE OPINION. 10 December 2008 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 10 December 2008 VIRAFERONPEG 50 µg/ 0.5 ml powder and solvent for injectable solution Pack of 1 (CIP: 355 189.3)

More information

Pretreatment assessment of Chronic Hepatitis C and Compensated Cirrhosis and Indications for Therapy

Pretreatment assessment of Chronic Hepatitis C and Compensated Cirrhosis and Indications for Therapy Pretreatment assessment of Chronic Hepatitis C and Compensated Cirrhosis and Indications for Therapy Teerha Piratvisuth MD. Prince of Songkla University Treatment of chronic hepatitis C and response rates

More information

Intravenous drug use is currently the main transmission

Intravenous drug use is currently the main transmission A Prospective Controlled Study of Interferon-Based Therapy of Chronic Hepatitis C in Patients on Methadone Maintenance Stefan Mauss, 1 Florian Berger, 1 Joerg Goelz, 2 Bernhard Jacob, 3 and Günther Schmutz

More information

Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors

Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors Fred Poordad, MD The Texas Liver Institute Clinical Professor of Medicine University of Texas Health Science Center

More information

ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, ClinicalTrials.gov ID: NCT

ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, ClinicalTrials.gov ID: NCT ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, 2014 ClinicalTrials.gov ID: NCT00372385 Study Identification Unique Protocol ID: VX05-950-104EU Brief Title:

More information

.'URRENT THERAPEUTIC RESEARCt

.'URRENT THERAPEUTIC RESEARCt .'URRENT THERAPEUTIC RESEARCt VOLUME 66, NUMBER 5, SEPTEMBER/OCTOBER 2005 Clinical Experience with Nonstandard Doses of Interferon Alfa-2b and Ribavirin in the Treatment of Chronic Hepatitis C Infection:

More information

eltrombopag (Promacta )

eltrombopag (Promacta ) Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the Company ), unless otherwise provided

More information

Current Standard of Care for Naïve HCV Patients (SVR)

Current Standard of Care for Naïve HCV Patients (SVR) Hepatitis C: Non-responders Nikunj Shah, MD Associate Professor of medicine University of Illinois Medical center 1 Current Standard of Care for Naïve HCV Patients (SVR) 1 8 8 6 53 45 4 6 52 46 4 2 2 Peg

More information

Antiviral therapy guidelines for the general population

Antiviral therapy guidelines for the general population Discussion 10 Chapter 10 Hepatitis C a worldwide problem More than 170 million people worldwide suffer from chronic hepatitis C. Its prevalence is 2% in industrialized countries. 1 Approximately 20% of

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Goals for Hepatitis C Therapy Compared to PegIFN α/rbv, new treatment regimens for chronic hepatitis C should offer: Improved efficacy Efficacy

More information

Weight-Based Combination Therapy with Peginterferon α-2b and Ribavirin for Naïve, Relapser and Non-Responder Patients with Chronic Hepatitis C

Weight-Based Combination Therapy with Peginterferon α-2b and Ribavirin for Naïve, Relapser and Non-Responder Patients with Chronic Hepatitis C BJID 2006; 10 (October) 311 Weight-Based Combination Therapy with Peginterferon α-2b and Ribavirin for Naïve, Relapser and Non-Responder Patients with Chronic Hepatitis C Fernando Lopes Gonçales Jr. 1,

More information

Hepatitis C Update. Geri Brown, M.D. Associate Professor Department of Internal Medicine March 24, 2011

Hepatitis C Update. Geri Brown, M.D. Associate Professor Department of Internal Medicine March 24, 2011 Hepatitis C Update Geri Brown, M.D. Associate Professor Department of Internal Medicine March 24, 2011 Outline n Educational Objectives Epidemiology and Natural History of Hepatitis C Current Treatment

More information

Pegasys Ribavirin

Pegasys Ribavirin Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.08 Subsection: Anti-infective Agents Original Policy Date: January 1, 2006 Subject: Pegasys Ribavirin

More information

29th Viral Hepatitis Prevention Board Meeting

29th Viral Hepatitis Prevention Board Meeting 29th Viral Hepatitis Prevention Board Meeting Madrid, November 2006 Treatment of chronic hepatitis C José M. Sánchez-Tapias Liver Unit Hospital Clínic University of Barcelona Spain CHRONIC HEPATITIS C

More information

The decision to treat hepatitis C virus. Managing Hepatitis C REPORTS. Bruce R. Bacon, MD

The decision to treat hepatitis C virus. Managing Hepatitis C REPORTS. Bruce R. Bacon, MD Bruce R. Bacon, MD Abstract Availability of a drug regimen that eradicates the hepatitis C virus (HCV) in more than half of treated patients provides the medical community with a powerful new weapon to

More information

Olysio PegIntron Ribavirin

Olysio PegIntron Ribavirin Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.27 Subject: Olysio PegIntron Ribavirin Page: 1 of 7 Last Review Date: March 18, 2016 Olysio PegIntron

More information

SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN SECTION 2: OLYSIO with (PEGINTRON) AND RIBAVIRIN RATIONALE FOR INCLUSION IN PA PROGRAM

SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN SECTION 2: OLYSIO with (PEGINTRON) AND RIBAVIRIN RATIONALE FOR INCLUSION IN PA PROGRAM SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN SECTION 2: OLYSIO with (PEGINTRON) AND RIBAVIRIN RATIONALE FOR INCLUSION IN PA PROGRAM SECTION 1: OLYSIO with (PEGASYS) AND RIBAVIRIN Background Hepatitis

More information

Pharmacological management of viruses in obese patients

Pharmacological management of viruses in obese patients Cubist Pharmaceuticals The Shape of Cures to Come Pharmacological management of viruses in obese patients Dr. Dimitar Tonev, Medical Director UKINORD 1 Disclosures } The author is a pharmaceutical physician

More information

V.G. Bain, P. Marotta, K. Kaita, E. Yoshida, M. Swain, R. Bailey, A. Neumann, P. Cronin, J. McHutchison, E. Pulkstenis, M.

V.G. Bain, P. Marotta, K. Kaita, E. Yoshida, M. Swain, R. Bailey, A. Neumann, P. Cronin, J. McHutchison, E. Pulkstenis, M. COMPARABLE ANTIVIRAL RESPONSE RATES WITH ALBINTERFERON ALFA-2B DOSED AT Q2W OR Q4W INTERVALS IN NAIVE SUBJECTS WITH GENOTYPE 2 OR 3 CHRONIC HEPATITIS C V.G. Bain, P. Marotta, K. Kaita, E. Yoshida, M. Swain,

More information

Specifically Targeted Antiviral Therapy (STAT-C) for Patients With Chronic Hepatitis C

Specifically Targeted Antiviral Therapy (STAT-C) for Patients With Chronic Hepatitis C Specifically Targeted Antiviral Therapy (STAT-C) for Patients With Chronic Hepatitis C Zobair M. Younossi, MD, MPH, FACP, FACG Medscape Gastroenterology. 2007; 2007 Medscape Posted 06/01/2007 Introduction

More information

A "State-of-the-Art" Conference Hepatitis C: A Meeting Ground for the Generalist and the Specialist

A State-of-the-Art Conference Hepatitis C: A Meeting Ground for the Generalist and the Specialist A "State-of-the-Art" Conference Hepatitis C: A Meeting Ground for the Generalist and the Specialist Information regarding pathogenesis and appropriate management of chronic hepatitis C continues to evolve.

More information

2.0 Synopsis. ABT-333 M Clinical Study Report R&D/09/956

2.0 Synopsis. ABT-333 M Clinical Study Report R&D/09/956 2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: ABT-333 Volume: Name of Active Ingredient: Page: Sodium N-{6-[3-tert-butyl-5-(2,4-

More information

Chronic Hepatitis C. Risk Factors

Chronic Hepatitis C. Risk Factors Chronic Hepatitis C The hepatitis C virus is one of the most important causes of chronic liver disease in the United States. Almost 4 million Americans or 1.8 percent of the U.S. population have an antibody

More information

Assessment of the Efficacy of Reducing Peginterferon Alfa-2a and Ribavirin Dose on Virologic Response in Koreans with Chronic Hepatitis C

Assessment of the Efficacy of Reducing Peginterferon Alfa-2a and Ribavirin Dose on Virologic Response in Koreans with Chronic Hepatitis C ORIGINAL ARTICLE DOI: 10.3904/kjim.2009.24.3.203 Assessment of the Efficacy of Reducing Peginterferon Alfa-2a and Ribavirin Dose on Virologic Response in Koreans with Chronic Hepatitis C Jung Hyun Kwon

More information

Intron A (interferon alfa-2b) with ribavirin, (Copegus, Moderiba, Rebetol, Ribapak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths)

Intron A (interferon alfa-2b) with ribavirin, (Copegus, Moderiba, Rebetol, Ribapak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths) Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Intron A Ribavirin Page: 1 of 5 Last Review Date: November 30, 2018 Intron A Ribavirin Description

More information

Intron A (interferon alfa-2b) with ribavirin, (Moderiba, Rebetol, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths)

Intron A (interferon alfa-2b) with ribavirin, (Moderiba, Rebetol, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths) Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.06 Subject: Intron A Ribavirin Page: 1 of 6 Last Review Date: March 18, 2016 Intron A Ribavirin Description

More information

Management of chronic hepatitis C treatment failures: role of consensus interferon

Management of chronic hepatitis C treatment failures: role of consensus interferon REVIEW Management of chronic hepatitis C treatment failures: role of consensus interferon Stevan A Gonzalez 1 Emmet B Keeffe 2 1 Division of Hepatology, Baylor Regional Transplant Institute, Baylor All

More information

Promacta (eltrombopag)

Promacta (eltrombopag) Promacta (eltrombopag) Policy Number: 5.01.542 Last Review: 5/2018 Origination: 6/2013 Next Review: 5/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Promacta

More information

Drug Class Monograph

Drug Class Monograph Drug Class Monograph Class: Chronic Hepatitis B Drug: Baraclude (entecavir), Epivir (lamivudine), Hepsera (adefovir), Intron A (interferon alfa- 2b), Pegasys (peginterferon alfa-2a), Tyzeka (telbivudine),

More information

Hepatitis C Management and Treatment

Hepatitis C Management and Treatment Hepatitis C Management and Treatment Kaya Süer Near East University Faculty of Medicine Infectious Diseases and Clinical Microbiology 1 Discovery of Hepatitis C Key facts Hepatitis C: the virus can cause

More information

Ribavirin (Medicare Prior Authorization)

Ribavirin (Medicare Prior Authorization) Prior Authorization Form ARKANSAS BLUE CROSS AND BLUE SHIELD Medi-Pak Rx (PDP), Medi-Pak Advantage (PFFS), and Medi-Pak Advantage PPO Ribavirin (Medicare Prior Authorization) This fax machine is located

More information

Appendix This appendix was part of the submitted manuscript and has been peer reviewed. It is posted as supplied by the authors.

Appendix This appendix was part of the submitted manuscript and has been peer reviewed. It is posted as supplied by the authors. Appendix This appendix was part of the submitted manuscript and has been peer reviewed. It is posted as supplied by the authors. Appendix to: Thompson AJV; Expert panel representing the Gastroenterological

More information

Hepatitis C Treatment

Hepatitis C Treatment Hepatitis C Treatment Standard of care & Managing advrse events Mohssen Nassiri Toosi, MD A s s o c i a t e P ro f e s s o r Of Internal M e d i c i n e Te h r a n U n i v e r s i t y O f M e d i c a l

More information

Management of Incidental Hepatitis C Virus Infection

Management of Incidental Hepatitis C Virus Infection The new england journal of medicine Clinical Decisions Interactive at nejm.org Management of Incidental Hepatitis C Virus Infection This interactive feature addresses the diagnosis or management of a clinical

More information

HEPATITIS C TREATMENT GUIDANCE

HEPATITIS C TREATMENT GUIDANCE HEPATITIS C TREATMENT GUIDANCE These guidelines have been produced based on the NICE Guidance TA200 Peginterferon alfa and ribavirin for the treatment of chronic hepatitis c and the summaries of product

More information

Should Elderly CHC Patients (>70 years old) be Treated?

Should Elderly CHC Patients (>70 years old) be Treated? Should Elderly CHC Patients (>70 years old) be Treated? Deepak Amarapurkar Consultant Gastroenterologist & Hepatologist Bombay Hospital & Medical Research Center, Mumbai & Jagjivanram Western Railway Hospital,

More information

Emerging Approaches for the Treatment of Hepatitis C Virus

Emerging Approaches for the Treatment of Hepatitis C Virus Emerging Approaches for the Treatment of Hepatitis C Virus Gap Analysis 1 Physicians may not be sufficiently familiar with the latest guidelines for chronic HCV treatment, including the initiation and

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium pegylated interferon α 2b (ViraferonPeg ), 50, 80, 100, 120 or 150 micrograms powder for solution for injection in pre-filled pen, in combination with ribavirin (Rebetol ),

More information

Direct-Acting Antiviral Therapy for Hepatitis C: Attitudes Regarding Future Use

Direct-Acting Antiviral Therapy for Hepatitis C: Attitudes Regarding Future Use DOI 10.1007/s10620-011-1604-3 ORIGINAL ARTICLE Direct-Acting Antiviral Therapy for Hepatitis C: Attitudes Regarding Future Use Paul J. Gaglio Noah Moss Camille McGaw John Reinus Received: 15 December 2010

More information

V. Hepatitis C Treatment

V. Hepatitis C Treatment V. Hepatitis C Treatment Summary The current standard of treatment for hepatitis C virus (HCV) is a combination of two drugs: pegylated interferon and ribavirin. The virological response rate, treatment

More information

Technology appraisal guidance Published: 22 September 2010 nice.org.uk/guidance/ta200

Technology appraisal guidance Published: 22 September 2010 nice.org.uk/guidance/ta200 Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C Technology appraisal guidance Published: 22 September 2010 nice.org.uk/guidance/ta200 NICE 2018. All rights reserved. Subject to

More information

Australasian Professional Society on Alcohol and other Drugs, Annual Conference 2016 Sydney Australia

Australasian Professional Society on Alcohol and other Drugs, Annual Conference 2016 Sydney Australia Efficacy and safety of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic HCV genotype 1 infection receiving opioid substitution therapy: Analysis of Phase 3 ION trials J Grebely

More information

Peginterferon Alfa-2b and Ribavirin for the Treatment of Chronic Hepatitis C in Blacks and Non-Hispanic Whites

Peginterferon Alfa-2b and Ribavirin for the Treatment of Chronic Hepatitis C in Blacks and Non-Hispanic Whites original article Peginterferon Alfa-2b and Ribavirin for the Treatment of Chronic Hepatitis C in and Andrew J. Muir, M.D., M.H.S., Jeffrey D. Bornstein, M.D., and Paul G. Killenberg, M.D., for the Atlantic

More information

Hepatitis B Prior Authorization Policy

Hepatitis B Prior Authorization Policy Hepatitis B Prior Authorization Policy Line of Business: Medi-Cal P&T Approval Date: November 15, 2017 Effective Date: January 1, 2018 This policy has been developed through review of medical literature,

More information

Conventional Interferon Alfa-2b and Ribavirin for 12 Versus 24 Weeks in HCV Genotype 2 or 3

Conventional Interferon Alfa-2b and Ribavirin for 12 Versus 24 Weeks in HCV Genotype 2 or 3 ORIGINAL ARTICLE Conventional Interferon Alfa-2b and Ribavirin for 12 Versus 24 Weeks in HCV Genotype 2 or 3 Javed Iqbal Farooqi and Rukhsana Javed Farooqi* ABSTRACT Objective: To determine the efficacy

More information

Yun Jung Kim, Byoung Kuk Jang, Eun Soo Kim, Kyung Sik Park, Kwang Bum Cho, Woo Jin Chung, and Jae Seok Hwang

Yun Jung Kim, Byoung Kuk Jang, Eun Soo Kim, Kyung Sik Park, Kwang Bum Cho, Woo Jin Chung, and Jae Seok Hwang The Korean Journal of Hepatology 2012;18:41-47 http://dx.doi.org/10.3350/kjhep.2012.18.1.41 pissn: 1738-222X eissn: 2093-8047 Original Article Rapid normalization of alanine aminotransferase predicts viral

More information

Parent drug: hours. Not reported Parent drug: 0.4 hours Major metabolite (GS ): 27 hours. ~61% to 65% bound to human plasma proteins

Parent drug: hours. Not reported Parent drug: 0.4 hours Major metabolite (GS ): 27 hours. ~61% to 65% bound to human plasma proteins Brand Name: Sovaldi Generic Name: sofosbuvir Manufacturer 3 : Gilead Sciences Inc. Drug Class 1,2 : Antiinfective, Antihepaciviral, Anti-HCV, NS5B polymerase inhibitor Uses: Labeled 1,2,3,4,5 : Chronic

More information

Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: A comparison with genotype 1

Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: A comparison with genotype 1 Title Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: A comparison with genotype 1 Author(s) Hui, CK; Yuen, MF; Sablon, E; Chan, AOO; Wong, BCY; Lai, CL Citation Journal Of Infectious

More information

Peginterferon Alfa-2a Plus Ribavirin Is More Effective Than Peginterferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection

Peginterferon Alfa-2a Plus Ribavirin Is More Effective Than Peginterferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection GASTROENTEROLOGY 2010;138:116 122 Peginterferon Alfa-2a Plus Ribavirin Is More Effective Than Peginterferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection ANTONIO ASCIONE,* MASSIMO

More information

1.0 Abstract. Title. Keywords

1.0 Abstract. Title. Keywords 1.0 Abstract Title Real World Evidence of the Effectiveness of Paritaprevir/r Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients with Chronic Hepatitis C - An Observational Study in Austria (REAL) Keywords

More information

CHRONIC HCV TREATMENT: In Special Populations.

CHRONIC HCV TREATMENT: In Special Populations. CHRONIC HCV TREATMENT: In Special Populations. By Taher EL-ZANATY Prof. of Internal Medicine CAIRO UNIVERSITY Introduction: HCV is the major cause of chronic hepatitis in Egypt. Its end stage is liver

More information

CENTENE PHARMACY AND THERAPEUTICS DRUG REVIEW 3Q17 July August

CENTENE PHARMACY AND THERAPEUTICS DRUG REVIEW 3Q17 July August BRAND NAME Technivie GENERIC NAME Ombitasvir/paritaprevir/ritonavir MANUFACTURER AbbVie, Inc. DATE OF APPROVAL February 27, 2017 PRODUCT LAUNCH DATE Already available on the market REVIEW TYPE Review type

More information

HIV and Hepatitis C Virus Coinfection: Bad Bedfellows

HIV and Hepatitis C Virus Coinfection: Bad Bedfellows Perspective HIV and Hepatitis C Virus Coinfection: Bad Bedfellows Hepatitis C virus (HCV) infection is common in HIV-infected individuals and is responsible for increasing morbidity in these patients.

More information

Peginterferon Alfa-2b and Ribavirin for 12 vs. 24 Weeks in HCV Genotype 2 or 3

Peginterferon Alfa-2b and Ribavirin for 12 vs. 24 Weeks in HCV Genotype 2 or 3 original article Peginterferon Alfa-2b and Ribavirin for 12 vs. 24 Weeks in HCV Genotype 2 or 3 Alessandra Mangia, M.D., Rosanna Santoro, Bs.D., Nicola Minerva, M.D., Giovanni L. Ricci, M.D., Vito Carretta,

More information

Olysio Pegasys Ribavirin

Olysio Pegasys Ribavirin Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.28 Subject: Olysio Pegasys Ribavirin Page: 1 of 7 Last Review Date: March 18, 2016 Olysio Pegasys

More information

Pegasys Pegintron Ribavirin

Pegasys Pegintron Ribavirin Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.47 Subsection: Anti-infective nts Original Policy Date: January 1, 2019 Subject: Pegasys Pegintron

More information

Improving Treatment Success Rates for HCV in a Managed Care Setting

Improving Treatment Success Rates for HCV in a Managed Care Setting Improving Treatment Success Rates for HCV in a Managed Care Setting Bruce R. Bacon, MD James F. King MD Endowed Chair in Gastroenterology Professor of Internal Medicine Division of Gastroenterology and

More information

SYNOPSIS OF RESEARCH REPORT (PROTOCOL MV22009)

SYNOPSIS OF RESEARCH REPORT (PROTOCOL MV22009) SYNOPSIS OF RESEARCH REPORT 1066781 (PROTOCOL MV22009) COMPANY: F. Hoffmann-La Roche, Ltd ME OF FINISHED PRODUCT: Pegasys ME OF ACTIVE SUBSTANCE(S): Peginterferon alfa-2a (FOR TIOL AUTHORITY USE ONLY)

More information

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 Phase 3 Treatment-Naïve and Treatment-Experienced Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 EXPEDITION-1: Study Features EXPEDITION-1 Trial Design: Open-label, single-arm,

More information

Sovaldi (sofosbuvir) with Pegasys (peginterferon alfa-2a) and Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin)

Sovaldi (sofosbuvir) with Pegasys (peginterferon alfa-2a) and Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin) Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.25 Subject: Sovaldi Pegasys Ribavirin Page: 1 of 6 Last Review Date: December 8, 2017 Sovaldi Pegasys

More information

Monitoring of Viral Levels of Hepatitis. During Therapy. Gary L. Davis

Monitoring of Viral Levels of Hepatitis. During Therapy. Gary L. Davis Monitoring of Viral Levels of Hepatitis Gary L. Davis During Therapy Alpha interferon therapy of chronic hepatitis C is typically accompanied by a biphasic decrease in hepatitis C virus (HCV) RNA levels:

More information

Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C. Part review of NICE technology appraisal guidance 75 and 106

Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C. Part review of NICE technology appraisal guidance 75 and 106 Issue date: September 2010 Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C Part review of NICE technology appraisal guidance 75 and 106 National Institute for Health and Clinical

More information

CASE STUDY. Adverse Events in treatment chronic hepatitis C patients with PegInterferon and Ribavirin What would your management decision be?

CASE STUDY. Adverse Events in treatment chronic hepatitis C patients with PegInterferon and Ribavirin What would your management decision be? Adverse Events in treatment chronic hepatitis C patients with PegInterferon and Ribavirin What would your management decision be? CASE STUDY Pham Thi Thu Thuy MD, PhD Ho Chi Minh City Vietnam Serious Adverse

More information

PRACTICE GUIDELINES INTRODUCTION

PRACTICE GUIDELINES INTRODUCTION American Journal of Gastroenterology ISSN 0002-9270 C 2006 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2006.00754.x Published by Blackwell Publishing PRACTICE GUIDELINES Management and Treatment

More information

HEPATITIS C VIRUS (HCV) GENOTYPE TESTING

HEPATITIS C VIRUS (HCV) GENOTYPE TESTING CLINICAL GUIDELINES For use with the UnitedHealthcare Laboratory Benefit Management Program, administered by BeaconLBS HEPATITIS C VIRUS (HCV) GENOTYPE TESTING Policy Number: PDS - 027 Effective Date:

More information

Management of Chronic Hepatitis B in Asian Americans

Management of Chronic Hepatitis B in Asian Americans Management of Chronic Hepatitis B in Asian Americans Myron J Tong; UCLA, CA Calvin Q. Pan; Mount Sinai, NY Hie-Won Hann; Thomas Jefferson, PA Kris V. Kowdley; Virginia Mason, WA Steven Huy B Han; UCLA,

More information

Background: Narlaprevir (SCH )

Background: Narlaprevir (SCH ) Once Daily Narlaprevir (SCH 9518) in Combination with Peginterferon alfa-2b/ Ribavirin for Treatment-Naive Patients with Genotype-1 Chronic Hepatitis C: Interim Results from the NEXT-1 Study Vierling J,

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) PegIFN and RBV remain vital components of HCV therapy-- selected presentations from: Program Disclosure This activity has been planned and

More information

Clinical Criteria for Hepatitis C (HCV) Therapy

Clinical Criteria for Hepatitis C (HCV) Therapy Diagnosis Clinical Criteria for Hepatitis C (HCV) Therapy Must have chronic hepatitis C (HCV infection > 6 months), genotype and sub-genotype specified to determine the length of therapy; Liver biopsy

More information

Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy?

Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy? Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy? Prof. Teerha Piratvisuth NKC Institute of Gastroenterology and Hepatology Prince of

More information

Viral Hepatitis The Preventive Potential of Antiviral Therapy. Thomas Berg

Viral Hepatitis The Preventive Potential of Antiviral Therapy. Thomas Berg Viral Hepatitis The Preventive Potential of Antiviral Therapy Thomas Berg Therapeutic and preventive strategies in patients with hepatitis virus infection Treatment of acute infection Treatment of chronic

More information

CLINICAL ADVANCES IN LIVER, PANCREAS, AND BILIARY TRACT

CLINICAL ADVANCES IN LIVER, PANCREAS, AND BILIARY TRACT GASTROENTEROLOGY 2010;138:108 115 Randomized Study of Peginterferon- 2a Plus Ribavirin vs Peginterferon- 2b Plus Ribavirin in Chronic Hepatitis C MARIA GRAZIA RUMI,* ALESSIO AGHEMO,* GIAN MARIA PRATI,*

More information

Feature. Downloaded from by guest on 06 November 2018

Feature. Downloaded from   by guest on 06 November 2018 Hepatitis C Virus: Epidemiology, Diagnosis, and Patient Management Peter P. Chou, PhD, DABCC, FACB (Quest Diagnostics Nichols Institute, Chantilly, VA) DOI: 10.1309/BNK8PH8FEPJ0VCH2 Laboratory photo courtesy

More information

Sovaldi (sofosbuvir) with PegIntron (peginterferon alfa-2b) and Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin)

Sovaldi (sofosbuvir) with PegIntron (peginterferon alfa-2b) and Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin) Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.24 Subject: Sovaldi PegIntron Ribavirin Page: 1 of 6 Last Review Date: November 30, 2018 Sovaldi PegIntron

More information