2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B.
OBJECTIVE
The GLOBE trial has compared the efficacy and safety of telbivudine versus lamivudine treatment over 2 years in patients with chronic hepatitis B.


METHODS
Hepatitis B e antigen (HBeAg)-positive (n = 921) and HBeAg-negative (n = 446) patients received telbivudine or lamivudine once daily for 104 weeks. The primary outcome, assessed in the intent-to-treat population, was therapeutic response (hepatitis B virus DNA <5 log(10) copies/mL and either HBeAg loss or normalization of alanine aminotransferase [ALT] level).


RESULTS
The therapeutic response to telbivudine was superior to that of lamivudine in HBeAg-positive (63% vs 48%; P < .001) and HBeAg-negative (78% vs 66%; P = .007) patients. HBeAg-positive patients given telbivudine also had better outcomes compared with lamivudine in terms of nondetectable viremia (< 300 copies/mL) at 55.6% versus 38.5% (P < .001), HBeAg loss at 35.2% versus 29.2% (P = .056), and viral resistance at 25.1% versus 39.5% (P < .001). Hepatitis B e antigen seroconversion was 29.6% versus 24.7% (P = .095) in all patients and 36% versus 27% (P = .022) in patients with baseline ALT level > or = 2 times normal. Telbivudine-treated HBeAg-negative patients showed higher rates of nondetectable viremia compared with lamivudine at 82.0% versus 56.7% (P < .001) and less resistance at 10.8% versus 25.9% (P < .001). Adverse events occurred with similar frequency, whereas grade 3/4 increases in creatine kinase levels were more common in patients given telbivudine (12.9% vs 4.1%, P < .001). Multivariate logistic regression analyses identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes.


CONCLUSIONS
Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period.
Liaw
Yun-Fan
YF
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. liveryfl@so-net.net.tw
Gane
Edward
E
Leung
Nancy
N
Zeuzem
Stefan
S
Wang
Yuming
Y
Lai
Ching Lung
CL
Heathcote
E Jenny
EJ
Manns
Michael
M
Bzowej
Natalie
N
Niu
Junqi
J
Han
Steven-Huy
SH
Hwang
Seong Gyu
SG
Cakaloglu
Yilmaz
Y
Tong
Myron J
MJ
Papatheodoridis
George
G
Chen
Yagang
Y
Brown
Nathaniel A
NA
Albanis
Efsevia
E
Galil
Karin
K
Naoumov
Nikolai V
NV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D014943:Global Health; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012044:Regression Analysis; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D019259:Lamivudine; D000410:Alanine Transaminase; D013936:Thymidine