- Email: [email protected]
919 ENTECAVIR (ETV) THERAPY IN CHRONIC HEPATITIS B PATIENTS PREVIOUSLY TREATED WITH ADEFOVIR (ADV) WITH INCOMPLETE RESPONSE ON-TREATMENT OR RELAPSE OFF-TREATMENT
S334
Poster Session − Saturday, April 25
918 CLEVUDINE DEMONSTRATES POTENT ANTIVIRAL ACTIVITY IN THE NAIVE CHRONIC HEPATITIS B PATIENTS June Sung Lee1 , E.T. Park2 , S.S. Kang3 , E.S. Gu4 , J.S. Kim5 , D.S. Jang6 , K.S. Lee7 , Jae-Su Lee8 , N.H. Park9 , C.H. Bae10 , S.K. Baik11 , B.J. Yu12 , S.H. Lee13 , E.J. Lee14 , S.I. Park15 , M. Bae16 , J.W. Shin9 , J.H. Choi17 , C. Gu18 , S.K. Moon19 , G.J. Chun20 , J.H. Kim21 , H.S. Kim22 , S.K. Choi23 . 1 Gastrointernal Dept., Inje University Paik Hospital, Seoul, 2 Inje University Paik Hospital, Busan, 3 Yegi Clinic, Seoul, 4 Hyoin Medical Clinic, Incheon, 5 Yonsei Somang Internal Medicine Clinic, Gympo, 6 Serim Hospital, Bupyung, 7 Hanmaeum Medical Center, Changwon, 8 Lee Jae-su Internal Medicine Clinic, Chongju, 9 Ulsan University Hospital, Ulsan, 10 Hopyung Asan Medical Clinic, Namyangju, 11 Yonsei University Wonju College of Medicine, Wonju, 12 Yu Byeong Jeon Internal Medicine Clinic, Gwangju, 13 Lee Soon Hyung Internal Medicine Clinic, Jeonju, 14 Lee Eun Jong Internal Medicine Clinic, Dongdu Cheon, 15 Donggunsan Hospital, Gunsan, 16 Hanil Hospital, Gwangju, 17 Hanmaum Medical Foundation Hana Hospital, Chongju, 18 Yeosu Chunnam Hospital, Yeosu, 19 Pohang SM Christianity Hospital, Pohang, 20 Gangneung Asan Hospital, Gangneung, 21 Gachon University Gil Hospital, Incheon, 22 Soonchunhyang University, Chunan, 23 Chonnam National University Hospital, Gwangju, South Korea E-mail: [email protected] Background and Aims: Clevudine has demonstrated antiviral potency in treatment-naive chronic HBV patients in the pivotal phase III trials. The objectives of the study were to evaluate the safety and efficacy of 1-year treatment with clevudine 30 mg in chronic hepatitis B patients. Methods: This study is a post-marketing surveillance study using case report form which was submitted to health authority. Data from 278 patients from several hospitals and clinics who were treated with clevudine for 1 year were collected to evaluate the efficacy and safety. Antiviral activity, biochemical and serological response, as well as clevudine resistance were assessed. Results: Analysis of individual data showed that HBV DNA levels were below 141,500 copies/mL in 95% of HBeAg positive patients and 100% of HBeAg negative patients. And the proportion of patients with HBV DNA lower than 2,000 copies/mL after 1-year treatment is 71%; HBeAg positive 69%, HBeAg negative 92%. The most of patients who showed HBV DNA below detection limit by each assay at week 24, showed sustained viral suppression upto week 48. The proportion of patients with normal ALT were 86% in both of HBeAg positive and HBeAg negative patients. The rates of HBeAg loss were 22%. Only 0.4% of patients showed viral rebound (>1 log10 increase from nadir) during treatment. Conclusions: Based on these results, we conclude that clevudine monotherapy demonstrates potent antiviral activity as well as biochemical and serological response with only 0.4% of viral rebound in the naive chronic hepatitis B patients.
919 ENTECAVIR (ETV) THERAPY IN CHRONIC HEPATITIS B PATIENTS PREVIOUSLY TREATED WITH ADEFOVIR (ADV) WITH INCOMPLETE RESPONSE ON-TREATMENT OR RELAPSE OFF-TREATMENT C.L. Lai1 , R. Elion2 , M. Sherman3 , H.W. Hann4 , D.L. Tyrell5 , C.W. Hsu6 , C.K. Tan7 , C.Y. Peng8 , N. Leung9 , K. Mercarni10 , H. Zhang10 , U.H. Iloeje10 , B. Kreter11 . 1 Department of Medicine, Queen Mary’s Hospital, University of Hong Kong, Hong Kong, China; 2 WhitmanWalker Clinic, Washington, WA, USA; 3 Toronto General Hospital, Toronto, Ontario, Canada; 4 Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA; 5 Health Sciences Center, Edmonton, AB, Canada; 6 Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan; 7 Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore; 8 China Medical University Hospital, Taichung, Taiwan; 9 Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China; 10 Research and Development, Bristol-Myers Squibb Company, Wallingford, CT, 11 Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA E-mail: [email protected] Background: The primary aims of antiviral therapy for the treatment of chronic hepatitis B (CHB) are the suppression of viral replication and remission of liver disease. However, a significant proportion of CHB patients treated with adefovir (ADV) have a suboptimal response to treatment, increasing the risks of disease progression and development of resistance. Due to the absence of cross-resistance in vitro, entecavir (ETV) therapy is recommended in patients not responding to ADV. Methods: Study ETV-079 was a randomized, open-label study comparing the viral kinetics, efficacy and safety of ETV (0.5 mg/day) with ADV (10 mg/day) in nucleoside-naive HBeAg(+) patients. After 48 weeks of treatment, patients from both arms of this study were eligible to enroll in the rollover study ETV-901 and receive treatment with ETV (1.0 mg/day). Results: Eighteen of the 24 ADV-treated patients who enrolled in ETV-901 from ETV-079 either failed to achieve undetectable HBV DNA (PCR < 300 copies/mL) or relapsed following ADV therapy and were subsequently switched to ETV. Among the patients who relapsed off-treatment between ETV-079 and -901, the treatment gap ranged from 1–128 days. At entry into ETV-901, the median HBV DNA for the whole group was 6.31 log10 copies/mL. Median exposure to ETV (1.0 mg) in ETV-901 was 46 weeks, and all 18 patients currently remain on study therapy. At Week 24, the mean reduction in HBV DNA was −4.54 log10 copies/mL and 8/16 (50%) achieved HBV DNA <300 copies/mL. Nine patients had reached Week 48 in ETV-901; all had reductions in HBV DNA to <104 copies/mL and 8/9 (89%) had HBV DNA <300 copies/mL. Genotypic resistance testing was not performed. The safety profile of ETV in these ADV-experienced patients remained consistent with the previously reported experience. Conclusions: The majority of patients who had incomplete virological response or experienced virological relapse following ADV treatment in study ETV-079 had rapid reductions in HBV DNA when switched to ETV in study ETV-901. HBV DNA levels continued to decline to <300 copies/mL in the majority of patients between 24 and 48 weeks of ETV treatment. 920 A NOVEL HEPATITIS B VIRUS MUTATION WITH RESISTANCE TO ADEFOVIR DIPIVOXIL IN PATIENTS WITH CHRONIC HEPATITIS B L.J. Liu, J.H. Wang, S.C. Du, L. Wei. Hepatology Insitute, Peking University People’s Hospital, Beijing, China E-mail: [email protected] Background and Aims: Up to today, two major adefovir dipivoxil (ADV)– resistant mutations of rtA181T/V and rtN236T have been identified in treating hepatitis B virus (HBV) infection. However, there are still some patients developing clinical and virologic evidences of breakthrough on ADV, in which no amino acid substitutions known to ADV resistance has been found. In this study, a novel mutation developed during ADV therapy
Poster Session − Saturday, April 25
918 CLEVUDINE DEMONSTRATES POTENT ANTIVIRAL ACTIVITY IN THE NAIVE CHRONIC HEPATITIS B PATIENTS June Sung Lee1 , E.T. Park2 , S.S. Kang3 , E.S. Gu4 , J.S. Kim5 , D.S. Jang6 , K.S. Lee7 , Jae-Su Lee8 , N.H. Park9 , C.H. Bae10 , S.K. Baik11 , B.J. Yu12 , S.H. Lee13 , E.J. Lee14 , S.I. Park15 , M. Bae16 , J.W. Shin9 , J.H. Choi17 , C. Gu18 , S.K. Moon19 , G.J. Chun20 , J.H. Kim21 , H.S. Kim22 , S.K. Choi23 . 1 Gastrointernal Dept., Inje University Paik Hospital, Seoul, 2 Inje University Paik Hospital, Busan, 3 Yegi Clinic, Seoul, 4 Hyoin Medical Clinic, Incheon, 5 Yonsei Somang Internal Medicine Clinic, Gympo, 6 Serim Hospital, Bupyung, 7 Hanmaeum Medical Center, Changwon, 8 Lee Jae-su Internal Medicine Clinic, Chongju, 9 Ulsan University Hospital, Ulsan, 10 Hopyung Asan Medical Clinic, Namyangju, 11 Yonsei University Wonju College of Medicine, Wonju, 12 Yu Byeong Jeon Internal Medicine Clinic, Gwangju, 13 Lee Soon Hyung Internal Medicine Clinic, Jeonju, 14 Lee Eun Jong Internal Medicine Clinic, Dongdu Cheon, 15 Donggunsan Hospital, Gunsan, 16 Hanil Hospital, Gwangju, 17 Hanmaum Medical Foundation Hana Hospital, Chongju, 18 Yeosu Chunnam Hospital, Yeosu, 19 Pohang SM Christianity Hospital, Pohang, 20 Gangneung Asan Hospital, Gangneung, 21 Gachon University Gil Hospital, Incheon, 22 Soonchunhyang University, Chunan, 23 Chonnam National University Hospital, Gwangju, South Korea E-mail: [email protected] Background and Aims: Clevudine has demonstrated antiviral potency in treatment-naive chronic HBV patients in the pivotal phase III trials. The objectives of the study were to evaluate the safety and efficacy of 1-year treatment with clevudine 30 mg in chronic hepatitis B patients. Methods: This study is a post-marketing surveillance study using case report form which was submitted to health authority. Data from 278 patients from several hospitals and clinics who were treated with clevudine for 1 year were collected to evaluate the efficacy and safety. Antiviral activity, biochemical and serological response, as well as clevudine resistance were assessed. Results: Analysis of individual data showed that HBV DNA levels were below 141,500 copies/mL in 95% of HBeAg positive patients and 100% of HBeAg negative patients. And the proportion of patients with HBV DNA lower than 2,000 copies/mL after 1-year treatment is 71%; HBeAg positive 69%, HBeAg negative 92%. The most of patients who showed HBV DNA below detection limit by each assay at week 24, showed sustained viral suppression upto week 48. The proportion of patients with normal ALT were 86% in both of HBeAg positive and HBeAg negative patients. The rates of HBeAg loss were 22%. Only 0.4% of patients showed viral rebound (>1 log10 increase from nadir) during treatment. Conclusions: Based on these results, we conclude that clevudine monotherapy demonstrates potent antiviral activity as well as biochemical and serological response with only 0.4% of viral rebound in the naive chronic hepatitis B patients.
919 ENTECAVIR (ETV) THERAPY IN CHRONIC HEPATITIS B PATIENTS PREVIOUSLY TREATED WITH ADEFOVIR (ADV) WITH INCOMPLETE RESPONSE ON-TREATMENT OR RELAPSE OFF-TREATMENT C.L. Lai1 , R. Elion2 , M. Sherman3 , H.W. Hann4 , D.L. Tyrell5 , C.W. Hsu6 , C.K. Tan7 , C.Y. Peng8 , N. Leung9 , K. Mercarni10 , H. Zhang10 , U.H. Iloeje10 , B. Kreter11 . 1 Department of Medicine, Queen Mary’s Hospital, University of Hong Kong, Hong Kong, China; 2 WhitmanWalker Clinic, Washington, WA, USA; 3 Toronto General Hospital, Toronto, Ontario, Canada; 4 Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA; 5 Health Sciences Center, Edmonton, AB, Canada; 6 Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan; 7 Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore; 8 China Medical University Hospital, Taichung, Taiwan; 9 Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China; 10 Research and Development, Bristol-Myers Squibb Company, Wallingford, CT, 11 Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA E-mail: [email protected] Background: The primary aims of antiviral therapy for the treatment of chronic hepatitis B (CHB) are the suppression of viral replication and remission of liver disease. However, a significant proportion of CHB patients treated with adefovir (ADV) have a suboptimal response to treatment, increasing the risks of disease progression and development of resistance. Due to the absence of cross-resistance in vitro, entecavir (ETV) therapy is recommended in patients not responding to ADV. Methods: Study ETV-079 was a randomized, open-label study comparing the viral kinetics, efficacy and safety of ETV (0.5 mg/day) with ADV (10 mg/day) in nucleoside-naive HBeAg(+) patients. After 48 weeks of treatment, patients from both arms of this study were eligible to enroll in the rollover study ETV-901 and receive treatment with ETV (1.0 mg/day). Results: Eighteen of the 24 ADV-treated patients who enrolled in ETV-901 from ETV-079 either failed to achieve undetectable HBV DNA (PCR < 300 copies/mL) or relapsed following ADV therapy and were subsequently switched to ETV. Among the patients who relapsed off-treatment between ETV-079 and -901, the treatment gap ranged from 1–128 days. At entry into ETV-901, the median HBV DNA for the whole group was 6.31 log10 copies/mL. Median exposure to ETV (1.0 mg) in ETV-901 was 46 weeks, and all 18 patients currently remain on study therapy. At Week 24, the mean reduction in HBV DNA was −4.54 log10 copies/mL and 8/16 (50%) achieved HBV DNA <300 copies/mL. Nine patients had reached Week 48 in ETV-901; all had reductions in HBV DNA to <104 copies/mL and 8/9 (89%) had HBV DNA <300 copies/mL. Genotypic resistance testing was not performed. The safety profile of ETV in these ADV-experienced patients remained consistent with the previously reported experience. Conclusions: The majority of patients who had incomplete virological response or experienced virological relapse following ADV treatment in study ETV-079 had rapid reductions in HBV DNA when switched to ETV in study ETV-901. HBV DNA levels continued to decline to <300 copies/mL in the majority of patients between 24 and 48 weeks of ETV treatment. 920 A NOVEL HEPATITIS B VIRUS MUTATION WITH RESISTANCE TO ADEFOVIR DIPIVOXIL IN PATIENTS WITH CHRONIC HEPATITIS B L.J. Liu, J.H. Wang, S.C. Du, L. Wei. Hepatology Insitute, Peking University People’s Hospital, Beijing, China E-mail: [email protected] Background and Aims: Up to today, two major adefovir dipivoxil (ADV)– resistant mutations of rtA181T/V and rtN236T have been identified in treating hepatitis B virus (HBV) infection. However, there are still some patients developing clinical and virologic evidences of breakthrough on ADV, in which no amino acid substitutions known to ADV resistance has been found. In this study, a novel mutation developed during ADV therapy