- Email: [email protected]
[633] Withdrawn
05G. VIRAL HEPATITIS
-
G) HEPATITIS C
-
CLINICAL (THERAPZ NEW COMPOUNDS, RESISTANCE)
Methods: The study group consisted of 45 patients with chronic hepatitis C (CHC) treated with PEGTFN and RBV The subjects were divided into 2 groups depending on the result of the treatment: responders (R) 30 patients (17 males, 13 females, mean age 40.63*2.43) and nonresponders (NR) 15 subjects (8 males, 7 females, mean age 49.07&3.08). The patients have liver biopsies performed at the beginning of the study and one year after the antiviral therapy. Liver specimens were formaldehyde-fixed, paraffin-embedded and histologically assessed according to Scheuer scoring system by two independent pathologists. Presence of NS3HCVAg was detected using monoclonal antibodies against HCV NS3 (Novocastra Ltd, Newcastle, UK). Results: In biopsy specimens obtained before the treatment HCVNS3Ag was detected in 27 pts from R and in 14 pts from NR group. After the treatment HCVAg was detected in 9/27 pts from R (P<0.001) and in 13/14 pts from NR group (P=0.976). In group R significant inflammatory activity (TA) and fibrosis regression after the treatment were observed (TA grading: 1-13.3%, TT-40%, TTT-46.6% vs. 1-76.6%, TT20.0%, 111-3.3%; P i 0.001; fibrosis staging: 0-3.3%, 1-16.6%, 11-50.0%, 111-23.3%, 1V-6.6% VS. 0-16.6%, 1-30.0‘%,,11-30.0%, 111-13.3%, lV-10.0%; P = 0.001). In NR group there was no significant changes in IA, but fibrosis progression was noted (1-20.0%, TT-66.6%, TIT- 13.3% vs.0-6.6%, 1-20.0%, TT-46.6%, TTT-20.0%, TV-6.6%; P = 0.005). Significant correlation between elimination of NS3HCVAg from liver tissue after the treatment and 1A (P=0.019) and fibrosis regression (P=0.005) was observed. Conclusions: Results of our study confirm HCV infection persistence in 30% of subjects achieving SVR. In patients who meet criteria of SVR, especially in those with undetectable HCVNS3Ag after the treatment, histological improvement can be observed. In non-responders fibrosis progression may occur even in one year after the unsuccessful treatment. -
S239
standard of care, without increasing the rates of anemia. A prospective study in which TBV is dosed according to body weight for the treatment of CHC is indicated.
-
16321 IMPACT OF TARlBAVlRlN EXPOSURE ON EFFICACY, ANEMIA RATES, AND GI SIDE EFFECTS WHEN USED WITH PEGYLATED INTERFERON ALFA-2b FOR THE TREATMENT OF CHRONIC HEPATITIS C P. Pockros’, M. Rodrigues-Torres’, Y. Lurie3, S. Gordon4, M . Shiffman5, Y. Li‘, B. Murphy‘. ‘Scri[)ys Clinic, La Jolb, CA, USA; 2Fnndacion de Inoestigacion de Diego, Santurce, Puerto Rico; .’Tel Aviv Sonraski Medical Centel; Tel Aviv, Israel; Willianz Beaumont Hospital, Royal Oak, MI; Virginia Commonwealth Univer~sih~, Richmond, VA; Vubant Pharmaceutical~sInternational, Costa Mesa, CA, USA E-mail: [email protected]
‘
Background: In a Phase 3 trial investigating the use of fixed-dose taribavirin (TBV) vs. weight-based ribavirin (RBV), in combination with pegylated interferon c(-2b, TBV-treated patients showed significantly lower anemia rates than those treated with RBV (5% vs. 24%, P 0.001) but failed to meet the primary non-inferiority efficacy endpoint when compared to RBV-treated patients (SVR rates 38% vs. 52%). This retrospective analysis was undertaken to examine the effect of TBV exposure according to body weight (mg/kg) on SVR rates, the development of anemia I0 gidL), and the rate of moderate-to-severe diarrhea. (hemoglobin i Methods: In this Phase 3 study, 970 patients were randomized in a 2:l ratio to receive either fixed-dose TBV or a weight-based dose RBV This posthoc intent-to-treat (ITT) analysis grouped patients into quartiles based on mgikg drug exposure, and then examined SVR rates, the rates of anemia and moderate-to-severe diarrhea. Results: See the table. Conclusions: Patients with higher mgikg exposures to TBV showed higher SVR rates. The rates of anemia remained constant as TBV exposure increased. The rates of moderate-to-severe diarrhea did not increase as exposure increased, suggesting that this gastrointestinal side effect may be a local gut phenomenon and not related to higher TBV plasma exposure. In this study, higher exposure to TBV leads to SVR rates similar to the current
mg/kg
n
SVR n (%)
Anemia rate n (“9)
Mod/severe diarrhea n (%)
13-15
179 147 182 138
57 (32) 46(31) 69 (38) 72 (52)
7 (4) 6(4) 12(7) 9 (7)
27 (15) 14 (10) 15 (8) 14 (10)
>IS-18 >I8
16331 Withdrawn
16341 A 7 YEAR RETROSPECTIVE AUDIT OF TREATMENT OUTCOMES FOR THE TREATMENT OF HEPATITIS C J. Rehman’ , M.H. Davies’ , S. Sheridan’, C. Wigglesworthl, S. Moreea’, C.E. Millson’ . ‘Department of Hepatology, St. James ‘s Uniuersity Hospital, Leeds, m s t Yorkshire; ’Departnzent of Gastroenterology and Hepatology, Bradfbrd Royal lnfirnzav, Bradfbrd, West Yorkshire, 7JK E-mail: jrehman@doctors,org.uk Background: ‘Real life’, non-‘sponsored’ data on treatment outcomes for hepatitis C is sparse especially between the two PEG-interferon based treatment regimens. Aims: To analyse retrospectively, baseline characteristics and treatment response rates in patients who had completed treatment for Hepatitis C. Methods: Between 2001 and 2006, 222 patients received either 40-kD (42 pts) or 121cD (180 pts) PEG-Interferon plus Ribavirin. Statistical tests included Chi-squared and Fisher exact test. Results: 146 patients were male, 169 Caucasians, median age at diagnosis were 40.3yrs (13.7-37.2) and diagnosis to treatment was 2.18 yrs (0.22-20.66). Commonest routes of acquisition were IVDU, Unknown and Blood transfusion with 66 patients having stage 2 5 disease on biopsy. Median BMI was 26.2 (17.3-57.8) and average weight loss with treatment being 3.73 kg (-26.5-+7.2). Average dose reductions were 14.4% (Interferon) and 13% (Ribavirin), 27 patients requiring EPO or GCSF support. 42 patients discontinued therapy for medical reason with 24 because non or partial response. A total of 12 were co-infected with either HTV or HBV, 27 diagnosed with diabetes and 66 having a history of excess alcohol consumption. ETVR and SVR’s were 73.4% and 55.9% respectively. Results by drug regimen showed that SVR was significantly higher for the 12kD than 40kD (60% and 36.1% respectively, p=0.008). By genotype no statistical difference was found, the trend was for 12kD regimen to achieve higher results than 401cD regimen (G1/4: 43.1% and 16.7%; G213: 73% and 55.5% respectively). Comparing the two regimens the 12kD Peg regimen showed greater SVR consistency across weight bands than 40 kD 5 ~ 6 0 %The . 40kD group tended Peg regimen ( 1 6 5 , >65<75, ~ 7 5 1 8 kg), to have patients with more advanced disease, in all weight categories. Comparing ETVR and SVR results by stage of disease and drug regimen there were no significant differences in each category (stageG4 or stage35 categories). Discontinuation rates from side effects in stageG4 disease with 40 kD Peg regimen (p 0.02) was found. Conclusion: Overall 121cD Peg combination therapy appears to offer a better SVR and a greater consistency across weight bands compared with 40 kD Peg combination therapy. Adjusted for stage of disease there is no statistical difference in the SVR between the 2 regimens.
<
-
G) HEPATITIS C
-
CLINICAL (THERAPZ NEW COMPOUNDS, RESISTANCE)
Methods: The study group consisted of 45 patients with chronic hepatitis C (CHC) treated with PEGTFN and RBV The subjects were divided into 2 groups depending on the result of the treatment: responders (R) 30 patients (17 males, 13 females, mean age 40.63*2.43) and nonresponders (NR) 15 subjects (8 males, 7 females, mean age 49.07&3.08). The patients have liver biopsies performed at the beginning of the study and one year after the antiviral therapy. Liver specimens were formaldehyde-fixed, paraffin-embedded and histologically assessed according to Scheuer scoring system by two independent pathologists. Presence of NS3HCVAg was detected using monoclonal antibodies against HCV NS3 (Novocastra Ltd, Newcastle, UK). Results: In biopsy specimens obtained before the treatment HCVNS3Ag was detected in 27 pts from R and in 14 pts from NR group. After the treatment HCVAg was detected in 9/27 pts from R (P<0.001) and in 13/14 pts from NR group (P=0.976). In group R significant inflammatory activity (TA) and fibrosis regression after the treatment were observed (TA grading: 1-13.3%, TT-40%, TTT-46.6% vs. 1-76.6%, TT20.0%, 111-3.3%; P i 0.001; fibrosis staging: 0-3.3%, 1-16.6%, 11-50.0%, 111-23.3%, 1V-6.6% VS. 0-16.6%, 1-30.0‘%,,11-30.0%, 111-13.3%, lV-10.0%; P = 0.001). In NR group there was no significant changes in IA, but fibrosis progression was noted (1-20.0%, TT-66.6%, TIT- 13.3% vs.0-6.6%, 1-20.0%, TT-46.6%, TTT-20.0%, TV-6.6%; P = 0.005). Significant correlation between elimination of NS3HCVAg from liver tissue after the treatment and 1A (P=0.019) and fibrosis regression (P=0.005) was observed. Conclusions: Results of our study confirm HCV infection persistence in 30% of subjects achieving SVR. In patients who meet criteria of SVR, especially in those with undetectable HCVNS3Ag after the treatment, histological improvement can be observed. In non-responders fibrosis progression may occur even in one year after the unsuccessful treatment. -
S239
standard of care, without increasing the rates of anemia. A prospective study in which TBV is dosed according to body weight for the treatment of CHC is indicated.
-
16321 IMPACT OF TARlBAVlRlN EXPOSURE ON EFFICACY, ANEMIA RATES, AND GI SIDE EFFECTS WHEN USED WITH PEGYLATED INTERFERON ALFA-2b FOR THE TREATMENT OF CHRONIC HEPATITIS C P. Pockros’, M. Rodrigues-Torres’, Y. Lurie3, S. Gordon4, M . Shiffman5, Y. Li‘, B. Murphy‘. ‘Scri[)ys Clinic, La Jolb, CA, USA; 2Fnndacion de Inoestigacion de Diego, Santurce, Puerto Rico; .’Tel Aviv Sonraski Medical Centel; Tel Aviv, Israel; Willianz Beaumont Hospital, Royal Oak, MI; Virginia Commonwealth Univer~sih~, Richmond, VA; Vubant Pharmaceutical~sInternational, Costa Mesa, CA, USA E-mail: [email protected]
‘
Background: In a Phase 3 trial investigating the use of fixed-dose taribavirin (TBV) vs. weight-based ribavirin (RBV), in combination with pegylated interferon c(-2b, TBV-treated patients showed significantly lower anemia rates than those treated with RBV (5% vs. 24%, P 0.001) but failed to meet the primary non-inferiority efficacy endpoint when compared to RBV-treated patients (SVR rates 38% vs. 52%). This retrospective analysis was undertaken to examine the effect of TBV exposure according to body weight (mg/kg) on SVR rates, the development of anemia I0 gidL), and the rate of moderate-to-severe diarrhea. (hemoglobin i Methods: In this Phase 3 study, 970 patients were randomized in a 2:l ratio to receive either fixed-dose TBV or a weight-based dose RBV This posthoc intent-to-treat (ITT) analysis grouped patients into quartiles based on mgikg drug exposure, and then examined SVR rates, the rates of anemia and moderate-to-severe diarrhea. Results: See the table. Conclusions: Patients with higher mgikg exposures to TBV showed higher SVR rates. The rates of anemia remained constant as TBV exposure increased. The rates of moderate-to-severe diarrhea did not increase as exposure increased, suggesting that this gastrointestinal side effect may be a local gut phenomenon and not related to higher TBV plasma exposure. In this study, higher exposure to TBV leads to SVR rates similar to the current
mg/kg
n
SVR n (%)
Anemia rate n (“9)
Mod/severe diarrhea n (%)
179 147 182 138
57 (32) 46(31) 69 (38) 72 (52)
7 (4) 6(4) 12(7) 9 (7)
27 (15) 14 (10) 15 (8) 14 (10)
>IS-18 >I8
16331 Withdrawn
16341 A 7 YEAR RETROSPECTIVE AUDIT OF TREATMENT OUTCOMES FOR THE TREATMENT OF HEPATITIS C J. Rehman’ , M.H. Davies’ , S. Sheridan’, C. Wigglesworthl, S. Moreea’, C.E. Millson’ . ‘Department of Hepatology, St. James ‘s Uniuersity Hospital, Leeds, m s t Yorkshire; ’Departnzent of Gastroenterology and Hepatology, Bradfbrd Royal lnfirnzav, Bradfbrd, West Yorkshire, 7JK E-mail: jrehman@doctors,org.uk Background: ‘Real life’, non-‘sponsored’ data on treatment outcomes for hepatitis C is sparse especially between the two PEG-interferon based treatment regimens. Aims: To analyse retrospectively, baseline characteristics and treatment response rates in patients who had completed treatment for Hepatitis C. Methods: Between 2001 and 2006, 222 patients received either 40-kD (42 pts) or 121cD (180 pts) PEG-Interferon plus Ribavirin. Statistical tests included Chi-squared and Fisher exact test. Results: 146 patients were male, 169 Caucasians, median age at diagnosis were 40.3yrs (13.7-37.2) and diagnosis to treatment was 2.18 yrs (0.22-20.66). Commonest routes of acquisition were IVDU, Unknown and Blood transfusion with 66 patients having stage 2 5 disease on biopsy. Median BMI was 26.2 (17.3-57.8) and average weight loss with treatment being 3.73 kg (-26.5-+7.2). Average dose reductions were 14.4% (Interferon) and 13% (Ribavirin), 27 patients requiring EPO or GCSF support. 42 patients discontinued therapy for medical reason with 24 because non or partial response. A total of 12 were co-infected with either HTV or HBV, 27 diagnosed with diabetes and 66 having a history of excess alcohol consumption. ETVR and SVR’s were 73.4% and 55.9% respectively. Results by drug regimen showed that SVR was significantly higher for the 12kD than 40kD (60% and 36.1% respectively, p=0.008). By genotype no statistical difference was found, the trend was for 12kD regimen to achieve higher results than 401cD regimen (G1/4: 43.1% and 16.7%; G213: 73% and 55.5% respectively). Comparing the two regimens the 12kD Peg regimen showed greater SVR consistency across weight bands than 40 kD 5 ~ 6 0 %The . 40kD group tended Peg regimen ( 1 6 5 , >65<75, ~ 7 5 1 8 kg), to have patients with more advanced disease, in all weight categories. Comparing ETVR and SVR results by stage of disease and drug regimen there were no significant differences in each category (stageG4 or stage35 categories). Discontinuation rates from side effects in stageG4 disease with 40 kD Peg regimen (p 0.02) was found. Conclusion: Overall 121cD Peg combination therapy appears to offer a better SVR and a greater consistency across weight bands compared with 40 kD Peg combination therapy. Adjusted for stage of disease there is no statistical difference in the SVR between the 2 regimens.
<