Switching
to Telbivudine Improves HBV Suppression in Lamivudine-experienced Patients
There
is growing recognition that maximizing virological suppression is an important
goal of chronic hepatitis B treatment,
but current therapies are limited by the emergence of resistant virus.
In
Phase II and III trials, the recently approved nucleoside analog telbivudine
(Tyzeka) produced significantly greater HBV suppression compared with lamivudine
(Epivir-HBV). A study presented at the recent American Association for the
Study of Liver Diseases (AASLD) annual meeting investigated whether patients receiving
lamivudine would benefit from a switch to telbivudine.
The study included
245 HBV surface antigen (HBsAg) positive patients who had previously received
lamivudine for 3-12 months at the time of screening. Subjects were either HBV
"e" antigen (HBeAg) positive or negative and had HBV DNA levels greater
than 3 log copies/mL and compensated liver disease.
Participants were
randomly assigned to either continue lamivudine (100 mg/day) or switch to telbivudine
(600 mg/day) for 1 year. The median HBV DNA levels at baseline were 5.04 and 5.27
log copies/mL in the telbivudine and lamivudine arms respectively. Patients were
stratified according to HBeAg status and duration of prior lamivudine use (12-24
weeks or 25-52 weeks). The primary efficacy endpoint was HBV DNA reduction at
Week 24.
Results
At Week 24, patients who switched to telbivudine experienced significantly greater
reductions in HBV DNA compared with patients who continued lamivudine (median
decreases of 1.66 log copies/mL vs 0.95 log copies/mL, respectively; P < 0.01).
HBV DNA
was suppressed to below 5 log copies/mL in 80% of patients who switched to telbivudine
vs 56% of those in the continued lamivudine group (P < 0.001).
HBV viral load became undetectable by PCR in 41% of patients in the telbivudine
arm compared with 31% receiving lamivudine (P = 0.14).
The difference was similar in all 4 randomization strata according to HBeAg status
and duration of prior lamivudine use.
In patients who were HBeAg positive at study entry, 9% and 7% lost HBeAg by Week
24 in the telbivudine and lamivudine groups, respectively (P = 0.77).
Both telbivudine and lamivudine were well tolerated.
Conclusion
"In
patients with persistent viremia during lamivudine therapy, switching to telbivudine
is associated with significantly improved HBV suppression," the researchers
concluded. "Longer follow-up will determine whether this results in continued
clinical benefits."
Middlemore Hospital, Auckland, New Zealand;
Holy Family Hospital, Nazareth, Israel; Ruijin Hospital, Shanghai, China; First
Affiliated Hospital, Hangzhou, China; Huashan Hospital, Shanghai, China; People's
Hospital, Peking University, Beijing, China; Bundang Cha Hospital, Kyunggi-Do,
South Korea; Bnai Zion Medical Center, Haifa , Israel; Beijing Friendship Hospital,
Beijing, China; Idenix Pharmaceuticals, Cambridge, MA; Novartis Pharmaceuticals,
East Hanover, NJ.
11/17/06
Reference E
Gane, R Safadi, Q Xie, and others. A Randomized Trial of Telbivudine (LdT) versus
Lamivudine in Lamivudine-Experienced Patients: Week 24 Primary Analysis. 57th
AASLD. Boston, MA. October 27-31, 2006. Abstract 1007.
At Week 24, patients who switched to telbivudine experienced significantly greater
reductions in HBV DNA compared with patients who continued lamivudine (median
decreases of 1.66 log copies/mL vs 0.95 log copies/mL, respectively; P < 0.01).
