- Email: [email protected]
828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE
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POSTERS
clinical trials. Only one trial (Zeuzem 2004) evaluated the efficacy of this therapy in PNALT; however, HCV-1 subjects were treated with low RBV dose (800 mg/day). Thus, the efficacy of the approved dosage of RBV (1000–1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Simulations based on generalised additive model (GAM) analysis suggest that SVR in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of ribavirin is administered (Snoeck et al, 2007). Aims of this study were (i) to evaluate the overall virological responses (EoTR, SVR) to combined antiviral treatment in HCV patients with PNALT, and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000–1200 mg/day) might achieve higher EVR than those obtained in previous RCT with lower RBV doses. Patients. 88 PNALT (53 females, range 22−60 yrs) were studied. 32 patients did harbour HCV type 1, 46 HCV-2, and 10 had HCV-3. Liver biopsy was performed in 72 patients, showing minimal fibrosis in all but 3 patients (F0−F1 Metavir). All patients received PEG interferon alfa2a 180 mg/wk plus RBV 800 mg/day for 24 wks (HCV 2 and 3 patients) or 1000–1200 mg/day for 48 wks (HCV-1 patients, according to bw). Persistent ALT normality was defined by at least 3 normal values two months apart over a 6 mo. observation period. Results: EoTR was seen in 81/88 pts (82%; 84% of HCV-1, 100% of HCV-2, 90% of HCV-3). To date, SVR has been evaluated in 63 pts (24 HCV-1 and 39 HCV-2); virological response was maintained in 37/39 HCV-2 patients (SVR 95%) and in 20/24 HCV-1 patients (83%). Side effects were not different from those observed among patients with elevated ALT levels treated in the same period. Conclusions. Antiviral treatment with PEG IFN plus RBV is safe and effective in patients with PNALT. Using standard RBV doses in patients with HCV-1, rates of SVR higher than those seen in patients with abnormal ALT can be achieved.
827 EFFICACY OF PEGINTERFERON ALPHA-2a AND RIBAVIRIN IN HIV/HCV CO-INFECTED PATIENTS: SUBANALYSIS OF HEPATYS, FRENCH NATIONAL SURVEY I. Ravaux1 , D. Ouzan2 , M. Rosenheim3 , M. Doffoel4 , P. Marcellin5 , J.M. Pawlotsky6 , C. Hayem7 , A. Pinta7 , M. Vray8 , M. Bourliere9 . 1 Infectious disease department, la Conception Hospital, Marseille, 2 Hepatology Unit, Tzank Institut, St Laurent du Var, 3 Infectious Disease Department, Piti´e-Salpˆetri`ere Hospital, Paris, 4 Hepatology Department, Civil Hospital, Strasbourg, 5 Hepatology Department, Beaujon Hospital, Clichy, 6 Virology Department, Henri Mondor Hospital, Creteil, 7 Roche, Neuilly, 8 Pasteur Institute, Paris, 9 Hepatology department, Saint-Joseph Hospital, France E-mail: [email protected] Background: In 2003, a longitudinal, multicenter prospective survey was initiated in order to assess the use and efficacy of Peginterferon alpha-2a in real life in chronic hepatitis C patients. Methods: Between November 2003 and December 2004, 334 physicians involved in C hepatitis management have included patients for whom a Peginterferon alpha-2a treatment was decided. Clinical and biological data were recorded at baseline and every three months, as well as PCR three months after the end of treatment for sustained virological response (SVR) evaluation. Results: Data from a total of 2101 patients were analyzed. Among these patients, 108 (5%) where HIV co-infected followed in hospital (87%) and in liberal practice (13%). Patients demography was as follows: mainly men (67%), mean age (±SD) 42 (±6) years, mean weight 67 (±13) Kg and 69% had a past history of injecting drug abuse. Regarding HIV infection, CD4 cells median was 407/mm3 and 84% of the patients received antiretroviral treatment. Previous or actual depression was present in 36% of the patients and an antidepressant treatment was prescribed in 26%. Almost every patient (93%, 100/108) had a liver disease evaluation, 81% (88/108) by liver biopsy. Cirrhosis was present in 23%. Genotypic
repartition was as follows: G1 48%, G2 4%, G3 35%, G4 11%, G5 1%. Majority of patients (64%) had never been treated. Higher doses of ribavirin (1000/1200 mg/day) were prescribed in 45% of the patients. SVR rates were obtained overall in 45% (37/83) and in 50% (24/48) of naive patients (36% for G1, 69% for G2,3). Patients with moderate or severe fibrosis had lower SVR rates compared to patients with minimal or no fibrosis: F0 100% (2/2), F1 67% (12/18), F2 44% (8/18) F3 42% (8/19) F4 31% (5/16). Conclusion: Efficacy of Peginterferon alpha-2a plus ribavirin used in real conditions in HIV/HCV co-infected patients is comparable to Presco trial results. 828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE K.R. Reddy1 , D. Messinger2 , M. Popescu3 , S.J. Hadziyannis4 . 1 Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; 2 IST GmbH, Mannheim, Germany; 3 Roche, Basel, Switzerland; 4 Henry Dunant Hospital, Athens, Greece E-mail: [email protected] Background: The demographics of HCV infection are shifting, with an increasing number of patients now over 50 years of age. To assess the impact of age on sustained virological response (SVR) we analyzed the data from two large phase III studies of PEG-IFN a-2a (40KD) plus ribavirin (RBV) (NV15942 and NV15801). Methods: Patients included in this analysis were HCV genotype 1 and had received 48 weeks of treatment with PEG-IFN a-2a (40KD) 180 mg/wk plus RBV 1000/1200 mg/day. SVR was defined as undetectable HCV RNA by qualitative PCR after 24 weeks of untreated follow-up. Results: Overall, the SVR rate in patients 50 years was 52% (n = 438) and 39% in the 131 patients who were >50 years (p = 0.007). SVR rates in patients aged >50 years were heterogeneous and varied according to previously well-established prognostic factors. In particular, SVR rates were higher in older patients without advanced fibrosis (44%), those with low baseline serum HCV RNA levels (57%), those patients who received 80% of the planned dose of PEG-IFN (53%) and those patients who received 60% of the planned dose of RBV (53%). Age did not influence whether patients completed therapy (76% of patients 50 years vs. 73% of patients >50 years [p = 0.6]). However, there was a trend towards lower cumulative PEG-IFN exposure in older patients (7235 mg in patients 50 vs. 6868 mg in patients >50 years [p = 0.0986]) and a significantly lower cumulative RBV exposure in older patients (304 g in patients 50 vs. 252 g in patients >50 [p < 0.0001]). In our study more patients >50 years had dose reductions resulting in <60% of target RBV exposure than patients 50 years (38% vs. 22%). Discontinuation rates due to any AE were similar in those 50 years (11%) and those >50 years (12%). Conclusions: SVR rates in subgroups of older patients with positive prognostic factors (such as those without advanced fibrosis, low HCV RNA levels) are comparable to younger patients, especially if high rates of adherence can be maintained.
POSTERS
clinical trials. Only one trial (Zeuzem 2004) evaluated the efficacy of this therapy in PNALT; however, HCV-1 subjects were treated with low RBV dose (800 mg/day). Thus, the efficacy of the approved dosage of RBV (1000–1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Simulations based on generalised additive model (GAM) analysis suggest that SVR in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of ribavirin is administered (Snoeck et al, 2007). Aims of this study were (i) to evaluate the overall virological responses (EoTR, SVR) to combined antiviral treatment in HCV patients with PNALT, and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000–1200 mg/day) might achieve higher EVR than those obtained in previous RCT with lower RBV doses. Patients. 88 PNALT (53 females, range 22−60 yrs) were studied. 32 patients did harbour HCV type 1, 46 HCV-2, and 10 had HCV-3. Liver biopsy was performed in 72 patients, showing minimal fibrosis in all but 3 patients (F0−F1 Metavir). All patients received PEG interferon alfa2a 180 mg/wk plus RBV 800 mg/day for 24 wks (HCV 2 and 3 patients) or 1000–1200 mg/day for 48 wks (HCV-1 patients, according to bw). Persistent ALT normality was defined by at least 3 normal values two months apart over a 6 mo. observation period. Results: EoTR was seen in 81/88 pts (82%; 84% of HCV-1, 100% of HCV-2, 90% of HCV-3). To date, SVR has been evaluated in 63 pts (24 HCV-1 and 39 HCV-2); virological response was maintained in 37/39 HCV-2 patients (SVR 95%) and in 20/24 HCV-1 patients (83%). Side effects were not different from those observed among patients with elevated ALT levels treated in the same period. Conclusions. Antiviral treatment with PEG IFN plus RBV is safe and effective in patients with PNALT. Using standard RBV doses in patients with HCV-1, rates of SVR higher than those seen in patients with abnormal ALT can be achieved.
827 EFFICACY OF PEGINTERFERON ALPHA-2a AND RIBAVIRIN IN HIV/HCV CO-INFECTED PATIENTS: SUBANALYSIS OF HEPATYS, FRENCH NATIONAL SURVEY I. Ravaux1 , D. Ouzan2 , M. Rosenheim3 , M. Doffoel4 , P. Marcellin5 , J.M. Pawlotsky6 , C. Hayem7 , A. Pinta7 , M. Vray8 , M. Bourliere9 . 1 Infectious disease department, la Conception Hospital, Marseille, 2 Hepatology Unit, Tzank Institut, St Laurent du Var, 3 Infectious Disease Department, Piti´e-Salpˆetri`ere Hospital, Paris, 4 Hepatology Department, Civil Hospital, Strasbourg, 5 Hepatology Department, Beaujon Hospital, Clichy, 6 Virology Department, Henri Mondor Hospital, Creteil, 7 Roche, Neuilly, 8 Pasteur Institute, Paris, 9 Hepatology department, Saint-Joseph Hospital, France E-mail: [email protected] Background: In 2003, a longitudinal, multicenter prospective survey was initiated in order to assess the use and efficacy of Peginterferon alpha-2a in real life in chronic hepatitis C patients. Methods: Between November 2003 and December 2004, 334 physicians involved in C hepatitis management have included patients for whom a Peginterferon alpha-2a treatment was decided. Clinical and biological data were recorded at baseline and every three months, as well as PCR three months after the end of treatment for sustained virological response (SVR) evaluation. Results: Data from a total of 2101 patients were analyzed. Among these patients, 108 (5%) where HIV co-infected followed in hospital (87%) and in liberal practice (13%). Patients demography was as follows: mainly men (67%), mean age (±SD) 42 (±6) years, mean weight 67 (±13) Kg and 69% had a past history of injecting drug abuse. Regarding HIV infection, CD4 cells median was 407/mm3 and 84% of the patients received antiretroviral treatment. Previous or actual depression was present in 36% of the patients and an antidepressant treatment was prescribed in 26%. Almost every patient (93%, 100/108) had a liver disease evaluation, 81% (88/108) by liver biopsy. Cirrhosis was present in 23%. Genotypic
repartition was as follows: G1 48%, G2 4%, G3 35%, G4 11%, G5 1%. Majority of patients (64%) had never been treated. Higher doses of ribavirin (1000/1200 mg/day) were prescribed in 45% of the patients. SVR rates were obtained overall in 45% (37/83) and in 50% (24/48) of naive patients (36% for G1, 69% for G2,3). Patients with moderate or severe fibrosis had lower SVR rates compared to patients with minimal or no fibrosis: F0 100% (2/2), F1 67% (12/18), F2 44% (8/18) F3 42% (8/19) F4 31% (5/16). Conclusion: Efficacy of Peginterferon alpha-2a plus ribavirin used in real conditions in HIV/HCV co-infected patients is comparable to Presco trial results. 828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE K.R. Reddy1 , D. Messinger2 , M. Popescu3 , S.J. Hadziyannis4 . 1 Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; 2 IST GmbH, Mannheim, Germany; 3 Roche, Basel, Switzerland; 4 Henry Dunant Hospital, Athens, Greece E-mail: [email protected] Background: The demographics of HCV infection are shifting, with an increasing number of patients now over 50 years of age. To assess the impact of age on sustained virological response (SVR) we analyzed the data from two large phase III studies of PEG-IFN a-2a (40KD) plus ribavirin (RBV) (NV15942 and NV15801). Methods: Patients included in this analysis were HCV genotype 1 and had received 48 weeks of treatment with PEG-IFN a-2a (40KD) 180 mg/wk plus RBV 1000/1200 mg/day. SVR was defined as undetectable HCV RNA by qualitative PCR after 24 weeks of untreated follow-up. Results: Overall, the SVR rate in patients 50 years was 52% (n = 438) and 39% in the 131 patients who were >50 years (p = 0.007). SVR rates in patients aged >50 years were heterogeneous and varied according to previously well-established prognostic factors. In particular, SVR rates were higher in older patients without advanced fibrosis (44%), those with low baseline serum HCV RNA levels (57%), those patients who received 80% of the planned dose of PEG-IFN (53%) and those patients who received 60% of the planned dose of RBV (53%). Age did not influence whether patients completed therapy (76% of patients 50 years vs. 73% of patients >50 years [p = 0.6]). However, there was a trend towards lower cumulative PEG-IFN exposure in older patients (7235 mg in patients 50 vs. 6868 mg in patients >50 years [p = 0.0986]) and a significantly lower cumulative RBV exposure in older patients (304 g in patients 50 vs. 252 g in patients >50 [p < 0.0001]). In our study more patients >50 years had dose reductions resulting in <60% of target RBV exposure than patients 50 years (38% vs. 22%). Discontinuation rates due to any AE were similar in those 50 years (11%) and those >50 years (12%). Conclusions: SVR rates in subgroups of older patients with positive prognostic factors (such as those without advanced fibrosis, low HCV RNA levels) are comparable to younger patients, especially if high rates of adherence can be maintained.