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Ribavirin
gender, HCV genotype, viral load, or pre-treatment Scheuer stage of fibrosis. Following stimulation with HCV NS 4 antigen responders had significantly higher IL-17 and IFNgamma response (p<0.05) compared to non-responders and treatment naïve subjects (Table 1). There was no statistical difference between non-responders and treatment naïve subjects. Conclusions: A differential CD4 + T cell IL-17 response is exhibited between responders and non-responders to conventional anti-viral therapy for hepatitis C. IL-17 may play a protective role in HCV, promoting viral clearance. Future prospective, longitudinal studies are warranted to evaluate the effects of antiviral therapy on the Th17 immune response in chronic HCV infection. IL-17 and IFN-Gamma Response Among Patient Populations
smoking status) were treated for up to 48 wks with PEG2b 1.5 or 1 μg/kg/week plus RBV 800-1400 mg/day, or PEG2a 180 μg/week plus RBV 1000-1200 mg/day. Patients with chronic obstructive pulmonary disease (COPD) were excluded from the study. Liver biopsy was required within 3 years of screening. Patients with virologic failure at week 12 (<2 log drop in HCV RNA from baseline) or 24 (detectable HCV RNA) terminated therapy. Sustained virologic response (SVR) rates were evaluated. Results: Of current smokers, ex-smokers, and non-smokers, 61%/64%/49% were males, median age 47/49/49 years, 18-19% blacks, 82%/84%/78% with baseline HCV-RNA >600,000 IU/mL, 12%/11%/9% had METAVIR F3/ 4 and 59%/60%/57% had steatosis. Mean baseline Hb levels were 15.2/15.0/14.7 g/dL with mean on-treatment Hb nadirs of 11.1/10.9/10.8 g/dL. Current smokers with F3/4 and/or steatosis had lower SVR rates than ex-smokers and non-smokers (Table). More non-smokers (31%) and ex-smokers (27%) developed anemia requiring dose reduction per protocol (Hb 8.5-<10 g/dL) than current smokers (22%); only 2%-3% required treatment discontinuation for Hb <8.5 g/dL. Erythropoietin stimulating agent (ESA) use was more common in exsmokers and non-smokers (17%/18%) compared with current smokers (13%). Conclusions: In the IDEAL study, smoking was not correlated with poor prognostic factors (increased fibrosis and/or steatosis). Among current smokers without COPD at baseline, SVR rates were not significantly lower. Sustained Virologic Response Rates, % (n/N)*
values expressed as mean +/-SEM in spots per million cells Su1886
Background: RESPOND-2, an international randomized, multicenter, double-blinded study, recently demonstrated that Boceprevir (B), an oral inhibitor of hepatitis C virus (HCV)-NS3 protease, when added to Peginterferon alpha-2b (P) and Ribavirin (R) leads to high sustained virologic response (SVR) rates in genotype 1 patients who failed prior treatment with P/R therapy. SVR rates of 21%, 59%, and 66% were reported in 403 patients randomized (1:2:2) to standard-of-care (SOC), response-guided therapy (RGT) and fixed-duration therapy (B/ PR48). Aim: To project the long-term clinical impact of treatment with SOC, RGT and B/ PR48 on patients included in RESPOND-2. Methods: We developed a Markov simulation model to project the lifetime incidence of liver complications in subjects in the following treatment regimens studied in RESPOND-2: (1) PR for 48 weeks (48W), (SOC); (2) PR for 4W, B/PR for 32W, with additional 12W of PR if subject had detectable HCV-RNA at treatment-week 8 (TW8), (RGT); and (3) PR for 4W, B/PR for 44W (B/PR48). All patients with detectable HCV-RNA at TW12 were discontinued for futility. If the patients achieved SVR, they were assumed to be cured of their viral disease; otherwise, they progressed through the HCV health states as per the natural history of chronic HCV disease. We stratified our results based on TW8 response since high SVR rates were reported amongst patients who were early responders. Forty-nine percent of subjects in Boceprevir-based regimens (46% of subjects in RGT and 52% of subjects in B/PR48) had undetectable HCV-RNA at TW8 compared to only 9% of subjects in SOC. Results: The following table summarizes the projected incidence of liver complications associated with chronic HCV by TW8 response for patients assigned to each treatment regimen: Conclusions: Boceprevir-based regimens are projected to substantially reduce the lifetime incidence of liver complications in treatmentfailure patients who are early responders and those who are HCV-RNA positive at TW8. Mean Projected Incidence of Liver Complications per 1000 by Response at TW8
AASLD Abstracts
Projecting the Long-Term Clinical Impact of Boceprevir in Patients With Chronic Hepatitis C Genotype-1 Who Failed Prior Treatment With Peginterferon/Ribavirin Jagpreet Chhatwal, Shannon A. Ferrante, Erik J. Dasbach, Antoine El Khoury, Margaret Burroughs, Bruce R. Bacon, Rafael Esteban, Clifford A. Brass
*62 patients missing smoking status. Su1888 Long-Term Clinical Value of Telaprevir for Treatment of Treatment-NaïVE and Treatment-Experienced Patients With Hepatitis C Virus (HCV) Infection: Projections Using Decision-Analytic Modeling Anita J. Brogan, Jeffrey D. Miller, Sandra E. Talbird, James R. Thompson, Baris Deniz Objective: Telaprevir (TVR) in combination with peginterferon/ribavirin (PR) is being investigated in the treatment of genotype 1 chronic HCV treatment-naïve (ADVANCE) and treatment-experienced (REALIZE) patients in phase 3 studies. Using an Excel®-based decisionanalytic model, potential long-term clinical value of TVR-based therapy was explored. Methods: A two part (Treatment; Post-Treatment) model was developed to project clinical outcomes of 12 week TVR-based therapy vs PR. Parallel hypothetical cohorts of 1,000 HCV genotype 1 patients were created: one cohort was assigned to TVR-based therapy and the other to PR for the model's Treatment part for treatment-naïve and treatment-experienced patients. Based on SVR rates from intention-to-treat analysis of ADVANCE and REALIZE trials, a proportion of the hypothetical patients in each cohort was deemed to achieve SVR for purposes of this analysis. The cohorts were then directed into the model's Post-Treatment part where long-term consequences of treatments were estimated for patients' remaining lifetimes using a cyclic Markov process. In any cycle, patients could remain in or transition among 4 pre-cirrhosis health states (METAVIR fibrosis scores F0-F3), cirrhosis (F4), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC), HCVrelated death, and non-HCV-related death. Patient characteristics at start of treatment, and SVR rates by baseline fibrosis score, were based on results from the phase 3 TVR clinical trials. Age- and gender-specific health state transition probabilities and mortality were obtained from published literature. Results: The model estimated that treatment-naïve and treatmentexperienced patients treated with TVR-based therapy lived on average 2.2 years (33.4 vs. 31.1 years) and 3.8 years (27.1 vs. 23.3 years) longer than patients in the PR cohort. Our model suggested potential reductions in major HCV-related clinical events of up to 55% of treatment-naïve patients and 64% of treatment-experienced patients over the lifetime of patients (Table 1). Conclusion: Results generated by our model suggest potentially substantial long-term clinical value of TVR-based combination therapy for genotype 1 HCV patients. Although assessment of real-world and long-term benefits of TVR will require further investigation, our model projected significant reductions in future HCV-related clinical burden in patients treated with TVR-based therapy compared with PR alone.
8 subjects randomized to SOC, 16 subjects in the RGT arm, and 7 subjects in the B/PR48 arm were missing TW8 values. Su1887 Effect of Cigarette Smoking on Virologic Response in Patients Treated for Chronic Hepatitis C (CHC) in the IDEAL Study Mary Pat Pauly, Fred Poordad, Alexandra L. Gibas, Bradley Freilich, Robert W. Reindollar, Terry D. Box, Robert M. Strauss, Donald Nelson, Natarajan Ravendhran, Coleman Smith, Eliot Godofsky, Venkata S. Goteti, Stephanie Noviello, Clifford A. Brass, Lisa D. Pedicone, Janice K. Albrecht, John McHutchison, Mark Sulkowski Background: Smoking in patients with CHC has been associated with increased fibrosis and steatosis, which are typically poor prognostic factors for peginterferon alfa (PEG) plus ribavirin (RBV) therapy. However, smokers may also have elevated hemoglobin levels (Hb) due to carbon monoxide, potentially decreasing protocol-required ribavirin dose reductions. This retrospective analysis evaluated the impact of baseline smoking status on sustained virologic response (SVR) rates in the IDEAL study. Methods: 3070 treatment-naive, CHC genotype 1 patients (1145 current smokers, 1121 ex-smokers, 742 non-smokers, 62 missing
S-947
AASLD Abstracts
smoking status) were treated for up to 48 wks with PEG2b 1.5 or 1 μg/kg/week plus RBV 800-1400 mg/day, or PEG2a 180 μg/week plus RBV 1000-1200 mg/day. Patients with chronic obstructive pulmonary disease (COPD) were excluded from the study. Liver biopsy was required within 3 years of screening. Patients with virologic failure at week 12 (<2 log drop in HCV RNA from baseline) or 24 (detectable HCV RNA) terminated therapy. Sustained virologic response (SVR) rates were evaluated. Results: Of current smokers, ex-smokers, and non-smokers, 61%/64%/49% were males, median age 47/49/49 years, 18-19% blacks, 82%/84%/78% with baseline HCV-RNA >600,000 IU/mL, 12%/11%/9% had METAVIR F3/ 4 and 59%/60%/57% had steatosis. Mean baseline Hb levels were 15.2/15.0/14.7 g/dL with mean on-treatment Hb nadirs of 11.1/10.9/10.8 g/dL. Current smokers with F3/4 and/or steatosis had lower SVR rates than ex-smokers and non-smokers (Table). More non-smokers (31%) and ex-smokers (27%) developed anemia requiring dose reduction per protocol (Hb 8.5-<10 g/dL) than current smokers (22%); only 2%-3% required treatment discontinuation for Hb <8.5 g/dL. Erythropoietin stimulating agent (ESA) use was more common in exsmokers and non-smokers (17%/18%) compared with current smokers (13%). Conclusions: In the IDEAL study, smoking was not correlated with poor prognostic factors (increased fibrosis and/or steatosis). Among current smokers without COPD at baseline, SVR rates were not significantly lower. Sustained Virologic Response Rates, % (n/N)*
values expressed as mean +/-SEM in spots per million cells Su1886
Background: RESPOND-2, an international randomized, multicenter, double-blinded study, recently demonstrated that Boceprevir (B), an oral inhibitor of hepatitis C virus (HCV)-NS3 protease, when added to Peginterferon alpha-2b (P) and Ribavirin (R) leads to high sustained virologic response (SVR) rates in genotype 1 patients who failed prior treatment with P/R therapy. SVR rates of 21%, 59%, and 66% were reported in 403 patients randomized (1:2:2) to standard-of-care (SOC), response-guided therapy (RGT) and fixed-duration therapy (B/ PR48). Aim: To project the long-term clinical impact of treatment with SOC, RGT and B/ PR48 on patients included in RESPOND-2. Methods: We developed a Markov simulation model to project the lifetime incidence of liver complications in subjects in the following treatment regimens studied in RESPOND-2: (1) PR for 48 weeks (48W), (SOC); (2) PR for 4W, B/PR for 32W, with additional 12W of PR if subject had detectable HCV-RNA at treatment-week 8 (TW8), (RGT); and (3) PR for 4W, B/PR for 44W (B/PR48). All patients with detectable HCV-RNA at TW12 were discontinued for futility. If the patients achieved SVR, they were assumed to be cured of their viral disease; otherwise, they progressed through the HCV health states as per the natural history of chronic HCV disease. We stratified our results based on TW8 response since high SVR rates were reported amongst patients who were early responders. Forty-nine percent of subjects in Boceprevir-based regimens (46% of subjects in RGT and 52% of subjects in B/PR48) had undetectable HCV-RNA at TW8 compared to only 9% of subjects in SOC. Results: The following table summarizes the projected incidence of liver complications associated with chronic HCV by TW8 response for patients assigned to each treatment regimen: Conclusions: Boceprevir-based regimens are projected to substantially reduce the lifetime incidence of liver complications in treatmentfailure patients who are early responders and those who are HCV-RNA positive at TW8. Mean Projected Incidence of Liver Complications per 1000 by Response at TW8
AASLD Abstracts
Projecting the Long-Term Clinical Impact of Boceprevir in Patients With Chronic Hepatitis C Genotype-1 Who Failed Prior Treatment With Peginterferon/Ribavirin Jagpreet Chhatwal, Shannon A. Ferrante, Erik J. Dasbach, Antoine El Khoury, Margaret Burroughs, Bruce R. Bacon, Rafael Esteban, Clifford A. Brass
*62 patients missing smoking status. Su1888 Long-Term Clinical Value of Telaprevir for Treatment of Treatment-NaïVE and Treatment-Experienced Patients With Hepatitis C Virus (HCV) Infection: Projections Using Decision-Analytic Modeling Anita J. Brogan, Jeffrey D. Miller, Sandra E. Talbird, James R. Thompson, Baris Deniz Objective: Telaprevir (TVR) in combination with peginterferon/ribavirin (PR) is being investigated in the treatment of genotype 1 chronic HCV treatment-naïve (ADVANCE) and treatment-experienced (REALIZE) patients in phase 3 studies. Using an Excel®-based decisionanalytic model, potential long-term clinical value of TVR-based therapy was explored. Methods: A two part (Treatment; Post-Treatment) model was developed to project clinical outcomes of 12 week TVR-based therapy vs PR. Parallel hypothetical cohorts of 1,000 HCV genotype 1 patients were created: one cohort was assigned to TVR-based therapy and the other to PR for the model's Treatment part for treatment-naïve and treatment-experienced patients. Based on SVR rates from intention-to-treat analysis of ADVANCE and REALIZE trials, a proportion of the hypothetical patients in each cohort was deemed to achieve SVR for purposes of this analysis. The cohorts were then directed into the model's Post-Treatment part where long-term consequences of treatments were estimated for patients' remaining lifetimes using a cyclic Markov process. In any cycle, patients could remain in or transition among 4 pre-cirrhosis health states (METAVIR fibrosis scores F0-F3), cirrhosis (F4), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC), HCVrelated death, and non-HCV-related death. Patient characteristics at start of treatment, and SVR rates by baseline fibrosis score, were based on results from the phase 3 TVR clinical trials. Age- and gender-specific health state transition probabilities and mortality were obtained from published literature. Results: The model estimated that treatment-naïve and treatmentexperienced patients treated with TVR-based therapy lived on average 2.2 years (33.4 vs. 31.1 years) and 3.8 years (27.1 vs. 23.3 years) longer than patients in the PR cohort. Our model suggested potential reductions in major HCV-related clinical events of up to 55% of treatment-naïve patients and 64% of treatment-experienced patients over the lifetime of patients (Table 1). Conclusion: Results generated by our model suggest potentially substantial long-term clinical value of TVR-based combination therapy for genotype 1 HCV patients. Although assessment of real-world and long-term benefits of TVR will require further investigation, our model projected significant reductions in future HCV-related clinical burden in patients treated with TVR-based therapy compared with PR alone.
8 subjects randomized to SOC, 16 subjects in the RGT arm, and 7 subjects in the B/PR48 arm were missing TW8 values. Su1887 Effect of Cigarette Smoking on Virologic Response in Patients Treated for Chronic Hepatitis C (CHC) in the IDEAL Study Mary Pat Pauly, Fred Poordad, Alexandra L. Gibas, Bradley Freilich, Robert W. Reindollar, Terry D. Box, Robert M. Strauss, Donald Nelson, Natarajan Ravendhran, Coleman Smith, Eliot Godofsky, Venkata S. Goteti, Stephanie Noviello, Clifford A. Brass, Lisa D. Pedicone, Janice K. Albrecht, John McHutchison, Mark Sulkowski Background: Smoking in patients with CHC has been associated with increased fibrosis and steatosis, which are typically poor prognostic factors for peginterferon alfa (PEG) plus ribavirin (RBV) therapy. However, smokers may also have elevated hemoglobin levels (Hb) due to carbon monoxide, potentially decreasing protocol-required ribavirin dose reductions. This retrospective analysis evaluated the impact of baseline smoking status on sustained virologic response (SVR) rates in the IDEAL study. Methods: 3070 treatment-naive, CHC genotype 1 patients (1145 current smokers, 1121 ex-smokers, 742 non-smokers, 62 missing
S-947
AASLD Abstracts