Predictors of Good Response to Telbivudine (Tyzeka) for Chronic Hepatitis B

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Predictors of Good Response to Telbivudine (Tyzeka) for Chronic Hepatitis B


Low baseline HBV viral load was the strongest overall predictor of favorable outcomes for patients treated with telbivudine (Tyzeka) in the GLOBE trial, with other predictive factors differing between hepatitis B "e" antigen (HBeAg) positive and negative participants.
By Liz Highleyman

The GLOBE trial was an international Phase 3 study comparing telbivudine versus lamivudine (Epivir-HBV) in more than 1300 chronic hepatitis B patients with compensated liver disease.

As previously reported, after 2 years, among HBeAg positive participants, the response rate was 63% in the telbivudine arm compared with 48% in the lamivudine arm. Among HBeAg negative patients, the corresponding rates were 78% and 66%, respectively. HBeAg positive patients taking telbivudine were more likely than lamivudine recipients to achieve undetectable HBV DNA (56% vs 39%) and HBeAg loss (35% vs 29%).

In the present analysis, reported in the July 2009 Journal of Hepatology, GLOBE investigators assessed all telbivudine recipients in the trial to determine predictors of optimal outcomes. The intent-to-treat population consisted of 458 HBeAg positive and 222 HBeAg negative patients.

Results

        Baseline HBV DNA < 9 log copies/mL or ALT > 2 times above normal were strong pre-treatment predictors of telbivudine response for HBeAg positive patients but not for HBeAg negative participants.
        Undetectable serum HBV DNA at treatment week 24 was the strongest predictor of better outcomes in both groups.
        A combination of pre-treatment characteristics and week 24 response identified subgroups with the best outcomes.
        HBeAg positive patients with baseline HBV DNA < 9 log copies/mL, ALT > 2 above normal, and undetectable HBV DNA at week 24 had the best response at year 2, with 89% having sustained undetectable HBV viral load, 52% experiencing HBeAg seroconversion, and only 1.8% developing telbivudine resistance.
        HBeAg negative patients with baseline HBV DNA < 7 log copies/mL and undetectable serum HBV DNA at treatment week 24 had a 91% rate of sustained undetectable HBV viral load at year 2, with 2.3% developing telbivudine resistance.

Based on these findings, the study authors concluded, "During telbivudine treatment, non-detectable serum HBV DNA at treatment week 24 is the strongest predictor for optimal outcomes at 2 years."
Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany; Middlemore Hospital, Auckland, New Zealand; Chang Gung Memorial Hospital, Chang Gung, University College of Medicine, Taipei, Taiwan; National University Hospital, Singapore; Saint Louis University, St. Louis, MO; Hospital Universitario Vall d'Hebron and CIBER-EHD, Barcelona, Spain; Phramongkutklao Hospital, Bangkok, Thailand; Albert Ludwigs University, Freiburg, Germany; NanFang Hospital, First Medical University of the PLA, Guangzhou, China; University of Miami, Miami, FL; Research and Education, Inc., San Diego, CA; Capital Medical University, Beijing, China; Groupe Hospitalier Pitie-Salpetriere, Paris, France; Idenix Pharmaceuticals, Cambridge, MA; Novartis Pharmaceuticals, East Hanover, NJ; Novartis Pharma AG, Basel, Switzerland.

8/04/09

References

S Zeuzem, E Gane, YF Liaw, and others. Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B. Journal of Hepatology 51(1): 11-20. July 2009. (Abstract).

HL Janssen and JG Reijnders. Treatment with nucleos(t)ide analogues in chronic hepatitis B: where does the road map lead us? Journal of Hepatology 51(1): 1-3. July 2009.