Gastroenterology
Volume 136, Issue 2 , Pages 486-495, February 2009

2-Year GLOBE Trial Results: Telbivudine Is Superior to Lamivudine in Patients With Chronic Hepatitis B

  • Yun–Fan Liaw

      Affiliations

    • Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
    • Corresponding Author InformationAddress requests for reprints to: Yun–Fan Liaw, MD, Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. fax: (886) 3-3282824
    • ,
  • Edward Gane

      Affiliations

    • Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
    • ,
  • Nancy Leung

      Affiliations

    • Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China
    • ,
  • Stefan Zeuzem

      Affiliations

    • Department of Medicine 1, J.W. Goethe Univeristy Hospital, Frankfurt, Germany
    • ,
  • Yuming Wang

      Affiliations

    • Xi Nan Hospital, Third Military Medical University, Chongqing, China
    • ,
  • Ching Lung Lai

      Affiliations

    • University Department of Medicine, Queen Mary Hospital, Hong Kong, China
    • ,
  • E. Jenny Heathcote

      Affiliations

    • Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Michael Manns

      Affiliations

    • Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    • ,
  • Natalie Bzowej

      Affiliations

    • Department of Liver Transplantation, California Pacific Medical Center, San Francisco, California
    • ,
  • Junqi Niu

      Affiliations

    • Department of Hepatology, First Hospital, University of Jilin, Guangzhou, China
    • ,
  • Steven–Huy Han

      Affiliations

    • Pfleger Liver Institute, UCLA School of Medicine, Los Angeles, California
    • ,
  • Seong Gyu Hwang

      Affiliations

    • Department of Internal Medicine, Pochon CHA University, Bundang Cha Hospital, Kyunggi-Do, Republic of Korea
    • ,
  • Yilmaz Cakaloglu

      Affiliations

    • Istanbul University, Istanbul, Turkey
    • ,
  • Myron J. Tong

      Affiliations

    • Phleger Liver Institute, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California
    • ,
  • George Papatheodoridis

      Affiliations

    • 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital, Athens, Greece
    • ,
  • Yagang Chen

      Affiliations

    • First Affiliated Hospital, Zhejiang University, Hangzhou, China
    • ,
  • Nathaniel A. Brown

      Affiliations

    • Idenix Pharmaceuticals, Cambridge, Massachusetts
    • ,
  • Efsevia Albanis

      Affiliations

    • Novartis AG, Basel, Switzerland
    • ,
  • Karin Galil

      Affiliations

    • Idenix Pharmaceuticals, Cambridge, Massachusetts
    • ,
  • Nikolai V. Naoumov

      Affiliations

    • Novartis AG, Basel, Switzerland
    • ,
  • The GLOBE Study Group

Received 29 August 2008; accepted 9 October 2008. published online 24 October 2008.

Background & Aims

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 log10 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 ≥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.

Abbreviations used in this paper: CK, creatine kinase, PCR, polymerase chain reaction, ULN, upper limit of normal

 

 Supported by Idenix Pharmaceuticals, Inc and Novartis Pharma AG. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis. Statistical analyses were performed by the study sponsor and independently by Quartesian, LLC (Princeton, NJ).

 The authors disclose the following: Y.–F.L. was a consultant for Bristol-Myers Squibb, GlaxoSmithKline, and Novartis and has received grant/research support from Bristol–Myers Squibb, Idenix, Novartis, and Gilead. E.G. received consulting fees from Gilead, GlaxoSmithKline, Merck, and Novartis and honoraria from GlaxoSmithKline, Idenix, Novartis, and Roche. N.L. is a speaker for Bristol–Myers Squibb, GlaxoSmithKline, Novartis, and Schering–Plough. S.Z. received consulting fees and/or lecture from Bristol–Myers Squibb, Gilead, GlaxoSmithKline, Novartis, Roche, and Schering–Plough. C.L.L. has received research grants from Idenix-Novartis. E.J.H. served on advisory board for Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Novartis, Schering-Plough; received research grants/funding from Axcan Pharma, Bristol-Myers-Squibb, Gilead Sciences, GlaxoSmithKline, Hoffman-LaRoche, Idenix, Novartis, Pharmasset, Schering-Plough, Vertex. M.M. received research grants, honoraria, and/or consultancy fees from Bristol–Myers Squibb, Boehringer–Ingelheim, Gilead, Idenix, Novartis, Roche, Schering–Plough, GSK, and Valeant. N.B. has received funding from Roche, Vertex, Schering, Gilead, Pharmasset, Connatus, Idenix, Novartis and speaker bureau fees from Gilead and Novartis. S.–H.H. received grant support, consultancy fees, and lecture fees from Novartis/Idenix. S.G.H. received consulting fees from Bukwang and research grants from Idenix, Valeant, BMS, and GSK. G.P. serves on advisory boards for Bristol–Myers Squibb, Gilead Sciences, Hoffmann–La Roche, Idenix–Novartis, has received research grants (from participation in phase 2/3 trials) from Gilead Sciences and Idenix–Novartis, has received unrestricted research grants from Hoffmann–La Roche, and is a speaker for Bristol–Myers Squibb, Gilead Sciences, Hoffmann–La Roche, and Idenix–Novartis. N.A.B. and K.G. were employees of Idenix at the time of this study. E.A. was an employee of Novartis at the time of the study. N.V.N. is an employee of Novartis. J.N., M.J.T., Y.W., Y. Cakaloglu, and Y. Chen report no conflicts of interest.

PII: S0016-5085(08)01861-1

doi:10.1053/j.gastro.2008.10.026

Refers to article:

  • Hepatitis B: A “GLOBAL” Health Challenge , 24 December 2008

    Robert J. Fontana
    Gastroenterology February 2009 (Vol. 136, Issue 2, Pages 389-392)

Gastroenterology
Volume 136, Issue 2 , Pages 486-495, February 2009