- Email: [email protected]
492 Adefovir dipivoxil (ADV) demonstrates sustained efficacy in HBeAg- chronic hepatitis B (CHB) patients
Posters
178
149~ SUSTAINED HBSAG SEROCONVERSION IN PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH PEGINTERFERON ~-2a (40 kDa) (PEGASYS ®) S. Hadziyannis I , G.K.K. Lau 2, R Marcellin 3, T. Piratvisuth4, G. Cooksley5, E Bonino 6, A. Chutaputti 7, M. Diago 8, R. Jin 9, N. P h c k 1°. 1Department of Medicine and Hepatology. Henry Dunant
Hospital, Athens, Greece, 2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," ~Service d'H@atologie, INSERM Unitg 481 and Centre de Recherches Claude Bernard sur les H@atites Virales, H@ital Beaujon, Clichy, France," 4Department of Medicine, Songklanakarin Hospital, Songkla, Thailand; 5Clinical Research Department, Royal Brisbane Hospital, Brisbane, Australia; 6IRCCS, Ospedale Maggiore di Milano Policlinico, Milan, Italy," 7Department of Medicine, Pramongkutklao Hospital, Bangkok, Thailand," 8Seccion de Hepatologia, Hospital General Universitario de Valencia, Valencia, Spain," 9Digestive Disease Department, Beijing You An Hospital, Beijing, China; 1°Roche, Welwyn, UK Background: HBsAg seroconversion (loss of HBsAg and appearance of anti-HBs) is considered to be the ultimate goal of anti-HBV treatment. It is, however, a rare event occurring in a negligible number of patients treated with nucleos(0ide analogues, mosdy in patients with HBV genotype A and after > 1 year of continuous therapy. Objectives: To describe HBsAg responses in 1351 patients with HBeAgpositive or -negative CHB who were enrolled in two randomised, partially double-blind, multinational studies comparing peginterferon o~-2a (40 kDa) (PEGASYS®), peginterferon (X-2a plus lamixatdine, and lamiwdine alone. Methods: HBeAg-positive (n 814) and -negative (n 537) patients received (1:1:1) either peginterferon o,-2a (180 ~tg once-weekly) + placebo, peginterferon ct-2a + lamivudine (100 nag once-daily) or lamivudine. Patients were treated for 48 weeks and assessed 24 weeks after the end of treatment (week 72). Patients were considered to have sustained HBsAg seroconversion only if they" were HBsAg-negative/anti-HBs-positive at week 72. Results: Over 75% of patients in the studies were of Asian origin; predominant HBV genotypes in the study populations were B (27%) and C (50%). Overall HBsAg seroconversion rates at week 72, and rates stratified by ethnicity and genotype are shown in the Table. HBsAg seroconversion only occurred in patients achieving HBeAg seroconversion - among responders with HBeAg seroconversion, the rate of HBsAg seroconversion was 10% with peginterferon (x-2a-containing therapy and 0% with lamivudine. gBs,g.g zeroconveraon at week 72 (24 v,vel6 aller the end of ~eatment) HBeA~poatlve CItB
PEGASYS
PEGASYS
+ placebo
+
Lanuvadane
PEGASYS
PEGASYS
+ placebo
+
(n= 271)
(n= 272)
(n= 177)
(n= 179)
(n= 181)
-4 5
-7 2
-5 8
-4 1
-5 0
-4 2
HBsA.~
S 0%)
8 0%)
o
5 (Wo)
s (2yo)
serocowmrsion AaanlOnental Caucasian H B V genotype
p= 0 004* 3/238 (1%0) 5/24 (21%)
p= 0 004* 5/238 (2%) 3/23 (13%)
-
p= 0 03* 3/108 (3%) 2266 (3%)
22112 (2%) 1/65 (2%)
5/23 (22%)
2/18 (11% 3
B C D
0/76(0%) 3/162 (2%) 0/9 (0%)
1/82(1%) 4/156 0%) 0/11 (0%)
ADEFOVIR DIPIVOXIL (ADV) DEMONSTRATES SUSTAINED EFFICACY IN HBeAg- CHRONIC HEPATITIS B (CHB) PATIENTS
S. Hadzivannis 1, N. Tassopoulos2, T.T. Chang3, J. Heathcote 4, G. Kitis 5, M. Rizzetto 6, R Marcellin 7, S .G. Lim 8 , S. Arterburn 9 , J. Ma 9, S. Xiong 9, C.L. Brosgart9, G. Currie 9. 1Henry Dunant Hospital, Athens, Greece,"
2Western Attica Hospital, Athens, Greece," 3National Cheng Kung Hospital, Taipei, Taiwan," 4Toronto Western Hospital, Toronto, ON, Canada," SGeorgios Papanikolaou Hospital, Thessaloniki, Greece; VAzienda OspedaBera San Giovanni Battista, Torino, Italy," 7H@ital Beaujon, Clichy, France," ~National University, Singapore, Singapore," 9Gilead Sciences, Inc., Foster City, CA, USA Background: Adefovir Dipivoxil (ADV) demonstrated efficacy and safety in 184 HBeAg- CHB patients enrolled in a 96-week randomized, placebocontrolled trial. Patients on ADV in the second 48 weeks were offered up to 3 additional years of ADV Objective: To evaluate the safety and efficacy of ADV over 192 weeks. Results: Baseline characteristics for patients randomized to receive ADV for 1st 96 weeks (n=79) and continuing open label ADV: 81% male; 70% Caucasian; 26% Asian; median age 47 years; median serum HBV DNA 7.081og10 copies/ml; median ALT: 99 IU/1 (2.3 x ULN). 70 and 67 patients continued ADV up to week 144 and week 192 respectively. Three patients had coTtfirmed elevations in serum creatinine >/-0.5mg/dl over 192 weeks. All resolved, one on treatment and two following discontinuation. No patients had phosphorus levels
-3.71 85% (51/60) 81% (44/54)
Lanuvudrne
larravudrne
(n= 271)
A
I•
HBeAg~ne~:atweCrib
larravudrne
M ~ : drop in tt BV-DNA at vmek 48 (lO~l0 cp/ml)
the major factor leading to HBsAg response, but rather the additional irnrnunornodulatory effect associated with peginterferon ct-2a (40kDa) (PEGASYS ®) treatment.
-
-
2/11 (18% 3
1/10 (10% 3
1/43 (2%) 2/63 (3%) 0/55 (0%)
2/41 (5%) 0/69 (0%) 0/54 (0%)
*vs larravudlne
Conclusions: In our study, patients treated with a peginterferon ~-2acontaining regimen for a defined duration achieved sustained HBsAg seroconversion, while patients treated with lamivudine did not. The magnitude of HBV-DNA suppression on treatment does not seem to be
Conclusions: Treatment with ADV 10my over 192 weeks resulted in significant and sustained reductions in HBV DNA levels with the majority of patients achieving prolonged HBV DNA suppression and sustained ALT normalizati on. ADV was generally well-tolerated with long-term treatment.
I•
LAMIVUDINE THERAPY FOR SEVERE ACUTE HEPATITIS B
F. Hasan I , S. Owaid I , M. All 2, H. Asker I , J. Alkhaldi t , R. Varghese I .
/Department of Medicine, Faculty of Medicine, Health Sciences Center, Safat, Kuwait," 2Department of Microbiology, Faculty of Medicine, Health Sciences Center, Shfat, Kuwait Background: severe acute hepatitis B can lead to fidminant hepatic failure (FMF) and death. Objective: To assess the efficacy and safety oflamivudine for the treatment of severe acute hepatitis B in immunocompetent patients.
178
149~ SUSTAINED HBSAG SEROCONVERSION IN PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH PEGINTERFERON ~-2a (40 kDa) (PEGASYS ®) S. Hadziyannis I , G.K.K. Lau 2, R Marcellin 3, T. Piratvisuth4, G. Cooksley5, E Bonino 6, A. Chutaputti 7, M. Diago 8, R. Jin 9, N. P h c k 1°. 1Department of Medicine and Hepatology. Henry Dunant
Hospital, Athens, Greece, 2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China," ~Service d'H@atologie, INSERM Unitg 481 and Centre de Recherches Claude Bernard sur les H@atites Virales, H@ital Beaujon, Clichy, France," 4Department of Medicine, Songklanakarin Hospital, Songkla, Thailand; 5Clinical Research Department, Royal Brisbane Hospital, Brisbane, Australia; 6IRCCS, Ospedale Maggiore di Milano Policlinico, Milan, Italy," 7Department of Medicine, Pramongkutklao Hospital, Bangkok, Thailand," 8Seccion de Hepatologia, Hospital General Universitario de Valencia, Valencia, Spain," 9Digestive Disease Department, Beijing You An Hospital, Beijing, China; 1°Roche, Welwyn, UK Background: HBsAg seroconversion (loss of HBsAg and appearance of anti-HBs) is considered to be the ultimate goal of anti-HBV treatment. It is, however, a rare event occurring in a negligible number of patients treated with nucleos(0ide analogues, mosdy in patients with HBV genotype A and after > 1 year of continuous therapy. Objectives: To describe HBsAg responses in 1351 patients with HBeAgpositive or -negative CHB who were enrolled in two randomised, partially double-blind, multinational studies comparing peginterferon o~-2a (40 kDa) (PEGASYS®), peginterferon (X-2a plus lamixatdine, and lamiwdine alone. Methods: HBeAg-positive (n 814) and -negative (n 537) patients received (1:1:1) either peginterferon o,-2a (180 ~tg once-weekly) + placebo, peginterferon ct-2a + lamivudine (100 nag once-daily) or lamivudine. Patients were treated for 48 weeks and assessed 24 weeks after the end of treatment (week 72). Patients were considered to have sustained HBsAg seroconversion only if they" were HBsAg-negative/anti-HBs-positive at week 72. Results: Over 75% of patients in the studies were of Asian origin; predominant HBV genotypes in the study populations were B (27%) and C (50%). Overall HBsAg seroconversion rates at week 72, and rates stratified by ethnicity and genotype are shown in the Table. HBsAg seroconversion only occurred in patients achieving HBeAg seroconversion - among responders with HBeAg seroconversion, the rate of HBsAg seroconversion was 10% with peginterferon (x-2a-containing therapy and 0% with lamivudine. gBs,g.g zeroconveraon at week 72 (24 v,vel6 aller the end of ~eatment) HBeA~poatlve CItB
PEGASYS
PEGASYS
+ placebo
+
Lanuvadane
PEGASYS
PEGASYS
+ placebo
+
(n= 271)
(n= 272)
(n= 177)
(n= 179)
(n= 181)
-4 5
-7 2
-5 8
-4 1
-5 0
-4 2
HBsA.~
S 0%)
8 0%)
o
5 (Wo)
s (2yo)
serocowmrsion AaanlOnental Caucasian H B V genotype
p= 0 004* 3/238 (1%0) 5/24 (21%)
p= 0 004* 5/238 (2%) 3/23 (13%)
-
p= 0 03* 3/108 (3%) 2266 (3%)
22112 (2%) 1/65 (2%)
5/23 (22%)
2/18 (11% 3
B C D
0/76(0%) 3/162 (2%) 0/9 (0%)
1/82(1%) 4/156 0%) 0/11 (0%)
ADEFOVIR DIPIVOXIL (ADV) DEMONSTRATES SUSTAINED EFFICACY IN HBeAg- CHRONIC HEPATITIS B (CHB) PATIENTS
S. Hadzivannis 1, N. Tassopoulos2, T.T. Chang3, J. Heathcote 4, G. Kitis 5, M. Rizzetto 6, R Marcellin 7, S .G. Lim 8 , S. Arterburn 9 , J. Ma 9, S. Xiong 9, C.L. Brosgart9, G. Currie 9. 1Henry Dunant Hospital, Athens, Greece,"
2Western Attica Hospital, Athens, Greece," 3National Cheng Kung Hospital, Taipei, Taiwan," 4Toronto Western Hospital, Toronto, ON, Canada," SGeorgios Papanikolaou Hospital, Thessaloniki, Greece; VAzienda OspedaBera San Giovanni Battista, Torino, Italy," 7H@ital Beaujon, Clichy, France," ~National University, Singapore, Singapore," 9Gilead Sciences, Inc., Foster City, CA, USA Background: Adefovir Dipivoxil (ADV) demonstrated efficacy and safety in 184 HBeAg- CHB patients enrolled in a 96-week randomized, placebocontrolled trial. Patients on ADV in the second 48 weeks were offered up to 3 additional years of ADV Objective: To evaluate the safety and efficacy of ADV over 192 weeks. Results: Baseline characteristics for patients randomized to receive ADV for 1st 96 weeks (n=79) and continuing open label ADV: 81% male; 70% Caucasian; 26% Asian; median age 47 years; median serum HBV DNA 7.081og10 copies/ml; median ALT: 99 IU/1 (2.3 x ULN). 70 and 67 patients continued ADV up to week 144 and week 192 respectively. Three patients had coTtfirmed elevations in serum creatinine >/-0.5mg/dl over 192 weeks. All resolved, one on treatment and two following discontinuation. No patients had phosphorus levels
-3.71 85% (51/60) 81% (44/54)
Lanuvudrne
larravudrne
(n= 271)
A
I•
HBeAg~ne~:atweCrib
larravudrne
M ~ : drop in tt BV-DNA at vmek 48 (lO~l0 cp/ml)
the major factor leading to HBsAg response, but rather the additional irnrnunornodulatory effect associated with peginterferon ct-2a (40kDa) (PEGASYS ®) treatment.
-
-
2/11 (18% 3
1/10 (10% 3
1/43 (2%) 2/63 (3%) 0/55 (0%)
2/41 (5%) 0/69 (0%) 0/54 (0%)
*vs larravudlne
Conclusions: In our study, patients treated with a peginterferon ~-2acontaining regimen for a defined duration achieved sustained HBsAg seroconversion, while patients treated with lamivudine did not. The magnitude of HBV-DNA suppression on treatment does not seem to be
Conclusions: Treatment with ADV 10my over 192 weeks resulted in significant and sustained reductions in HBV DNA levels with the majority of patients achieving prolonged HBV DNA suppression and sustained ALT normalizati on. ADV was generally well-tolerated with long-term treatment.
I•
LAMIVUDINE THERAPY FOR SEVERE ACUTE HEPATITIS B
F. Hasan I , S. Owaid I , M. All 2, H. Asker I , J. Alkhaldi t , R. Varghese I .
/Department of Medicine, Faculty of Medicine, Health Sciences Center, Safat, Kuwait," 2Department of Microbiology, Faculty of Medicine, Health Sciences Center, Shfat, Kuwait Background: severe acute hepatitis B can lead to fidminant hepatic failure (FMF) and death. Objective: To assess the efficacy and safety oflamivudine for the treatment of severe acute hepatitis B in immunocompetent patients.