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.
|
FDA-approved
Combination Therapies for Chronic HBV Infection
