Lamivudine
is an effective anti-HBV therapy, but its long-term benefits are limited by the
relatively rapid emergence of drug-resistant virus.
Study
1
Researchers
with the international GLOBE study reported 52-week results in the December 20,
2007 issue of the New England Journal of Medicine.
In
this Phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned
to receive 600 mg telbivudine or 100
mg lamivudine once daily.
The
primary efficacy endpoint was reduction of serum HBV DNA to fewer than 5 log10
copies/mL, along with loss of hepatitis B "e" antigen (HBeAg) and/or
alanine aminotransferase (ALT) normalization; histological response was also assessed.
Results
•
At week 52, a significantly higher proportion of HBeAg positive patients receiving
telbivudine experienced a therapeutic response than those receiving lamivudine
(75% vs 67%; P = 0.005).
•
The telbivudine arm also had a higher rate of histological response (65% vs 56%;
P = 0.01).
•
Telbivudine was non-inferior to lamivudine for these endpoints in HBeAg negative
patients as well.
•
In both HBeAg positive and HBeAg negative participants, telbivudine was superior
to lamivudine with respect to:
-
Mean reduction in HBV DNA from baseline;
- Proportion of patients with
undetectable HBV DNA by polymerase chain-reaction (PCR);
- Development
of drug resistance.
•
Elevated
creatine kinase levels (an indicator of possible muscle damage) were more common
in patients receiving telbivudine.
•
Elevated ALT and aspartate aminotransferase (AST) levels were more common in those
receiving lamivudine.
In
conclusion, the authors wrote, "Among patients with HBeAg positive chronic
hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly
higher in patients treated with telbivudine than in patients treated with lamivudine."
"In
both the HBeAg negative and the HBeAg positive groups, telbivudine demonstrated
greater HBV DNA suppression with less resistance than did lamivudine," they
added.
Study
2
In
the second study, reported in the December 13, 2007 advance online edition of
Hepatology, researchers compared the efficacy of telbivudine versus lamivudine
in Chinese patients.
In this double-blind Phase III trial, 332 patients
with compensated HBeAg positive or HBeAg negative chronic hepatitis B were randomly
assigned to receive 600 mg telbivudine or 100 mg lamivudine daily for 104 weeks.
The primary efficacy endpoint was reduction in serum HBV DNA at week 52.
Secondary endpoints included undetectable HBV DNA, HBeAg loss and seroconversion,
therapeutic response, and ALT normalization. Drug resistance and safety parameters
were also assessed.
Results
•
At week 52, among 290 HBeAg positive patients, mean reductions in HBV DNA were
significantly greater in telbivudine recipients compared with lamivudine recipients
(6.3 vs 5.5 log10; P < 0.001).
•
Significantly more telbivudine recipients achieved undetectable HBV DNA by PCR
(67% vs 38%; P < 0.001).
•
ALT normalization (87% vs 75%; P = 0.007), therapeutic response (85% vs 62%; P
= 0.001), and HBeAg loss (31% vs 20%; P = 0.047) were all significantly more frequent
in the telbivudine group.
•
Similar patterns were observed in the smaller HBeAg negative group (n = 42).
•
About half as many patients in the telbivudine group compared with the lamivudine
group developed drug-resistant virus, but the difference was not statistically
significant.
•
Clinical adverse events were similar in the 2 telbivudine and lamivudine arms.
Based
on these findings, the authors concluded, "In Chinese patients with chronic
hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and
clinical efficacy than lamivudine, with less [drug] resistance."
01/08/08
References
CL
Lai, E Gane, YF Liaw, and others. Telbivudine versus Lamivudine in Patients with
Chronic Hepatitis B. New England Journal of Medicine 357(25): 2576-2588.
December 20, 2007.
J
Hou, YK Yin, D Xu, and others. Telbivudine versus lamivudine in Chinese patients
with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial.
Hepatology. December 13, 2007 [Epub ahead of print].
