Telbivudine (Tyzeka)

StephenW

<http://www.hivandhepatitis.com/2 ... cs/0430_2010_c.html>

HIV and Hepatitis.com Coverage of the
45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010)
April 14 - 18, 2010, Vienna, Austria

Telbivudine (Tyzeka) Produces Better Outcomes than Lamivudine in Hepatitis B
Patients with Decompensated Cirrhosis
   
  SUMMARY: Telbivudine (Tyzeka) led to better outcomes than lamivudine
(Epivir-HBV) for chronic hepatitis B patients with decompensated cirrhosis,
increasing the likelihood of HBV viral load suppression and ALT normalization,
according to a study presented at the 45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010) this month in Vienna. In
this analysis, telbivudine had a safety profile similar to lamivudine and was
associated with improved liver and kidney function. Another study, however,
found that telbivudine in combination with pegylated interferon can cause
peripheral neuropathy.

   
By Liz Highleyman
Over years or decades, chronic hepatitis B can progress to advanced liver
disease, including hepatocellular carcinoma, cirrhosis, and liver failure.
Decompensated cirrhosis -- meaning the liver can no longer carry out its vital
functions -- is associated with high morbidity and mortality, yet treatment
options are limited.


Antiviral agents can lower HBV levels in people with advanced cirrhosis, but
they may cause side effects that patients with severe illness are unable to
tolerate. Lamivudine is generally well-tolerated, but it is prone to
resistance that can compromise long-term effectiveness.
Most people with decompensated cirrhosis patients have some degree of kidney
impairment, indicating that adefovir (Hepsera) and tenofovir (Viread), which
can worsen kidney dysfunction in susceptible individuals, should be used with
caution. (Another study presented at the EASL meeting, however, showed that
tenofovir/emtricitabine appears safe in patients with mild-to-moderate kidney
impairment after liver transplantation.)
Edward Gane from Middlemore Hospital in Auckland, New Zealand, and colleagues
conducted a study comparing treatment outcomes with telbivudine versus
lamivudine in decompensated chronic hepatitis B patients.
This double blind trial included 232 patients with decompensated liver
disease, defined as a Child-Turcotte-Pugh score above 7 and cirrhosis or
portal hypertension. About three-quarters were men, 65% were Asian, the median
age was about 50 years, and about 57% were hepatitis B "e" antigen (HBeAg)
negative.
Study participants were randomly assigned to receive 600 mg telbivudine or 100
mg lamivudine for 104 weeks.

Results
In a 2 year intent-to-treat analysis, 49% of patients receiving telbivudine
achieved undetectable HBV DNA (< 300 copies/mL), compared with 40% in the
lamivudine arm (P = 0.15, not a significant difference).
73% of participants in the telbivudine arm and 62% in the lamivudine arm
experienced ALT normalization (P = 0.25, also not significant).
Looking at a composite endpoint of undetectable HBV DNA and ALT
normalization, however, telbivudine performed significantly better than
lamivudine (34% vs 24%, respectively; P = 0.004)
28% of telbivudine recipients experienced viral breakthrough while on
therapy, compared with 37% of lamivudine recipients (P = 0.16).
At the end of treatment, about 75% of patients in both arms had stabilized or
improved liver disease, as indicated by changes from baseline in
Child-Turcotte-Pugh scores.
Kidney function (indicated by glomerular filtration rate) modestly improved
in the telbivudine arm, while worsening in the lamivudine arm.
Early (week 24) survival rates were similar in the 2 study arms, 96% with
telbivudine and 92% with lamivudine.
Long-term (week 104) survival rates were 87% and 79%, respectively, with a
trend toward statistical significance.
Serious adverse events were common, consistent with advanced liver disease,
and occurred with similar frequency in both arms (51% of telbivudine
recipients vs 59% of lamivudine recipients).
No cases of rhabdomyolysis (muscle damage due to drug toxicity) or lactic
acidosis (associated with mitochondrial toxicity) were reported.
Based on these findings, the investigators concluded, "In a large number of
patients with long term follow-up telbivudine was well tolerated with
stabilization of liver function and comparable tolerability to lamivudine."
Peripheral Neuropathy
Another study sounded a note of caution, however. Patrick Marcellin and
colleagues reported that telbivudine plus pegylated interferon led to a higher
rate of undetectable HBV viral load and greater reductions in HBeAg and
hepatitis B surface antigen (HBsAg) than either drug alone. However, patients
receiving combination therapy were more than twice as likely to experience
adverse events.
Of particular concern, peripheral neuropathy (nerve damage) developed sooner
and was more severe in the combination arm, leading to premature
discontinuation of the study. Telbivudine is a thymidine nucleoside analog, a
class of drugs associated with peripheral neuropathy, facial fat loss, and
other manifestations associated with mitochondrial toxicity in people treated
for HIV.
The investigators recommended that "[d]espite increased efficacy, concomitant
use of [pegylated interferon + telbivudine] should be avoided at present."


Investigator affiliations:
Gane study: Middlemore Hospital, Auckland, New Zealand; Department of Medicine
and Therapeutics, Chinese University of Hong Kong, Hong Kong, China; Sanjay
Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; Department
of Internal Medicine, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, Republic of Korea; Phramongkutklao Hospital, Bangkok,
Thailand; Holy Family Hospital, Nazareth & Hadassah Medical Center, Jerusalem,
Israel; Siriraj Hospital, Bangkok; Chiang Mai University, Faculty of Medicine,
Chiang Mai, Thailand; Sieff Government Hospital, Safed, Israel; Department of
Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India;
Novartis Pharma Corporation, East Hanover, NJ.

Marcellin study: Service d'Hépatologie, INSERM, Hôpital Beaujon, Clichy,
France; Novartis Pharma AG, Basel, Switzerland; Hannover Medical School,
Hannover, Germany; Kaohsiung Medical University, Kaohsiung, Taiwan ROC;
Clinical Trial Center, LKS Faculty of Medicine, University of Hong Kong, Hong
Kong, China; China Medical University Hospital, Taichung, Taiwan ROC;
Middlemore Hospital, Auckland, New Zealand; Hospital de Enfermedades
Infecciosas, Buenos Aires, Argentina.
4/30/10


Reference
EJ Gane, HL Chan, G Choudhuri, and others. Treatment of decompensated
HBV-cirrhosis: results from 2-years randomized trial with telbivudine or
lamivudine. 45th Annual Meeting of the European Association for the Study of
the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).

P Marcellin, C Avila, K Wursthorn, and others. Telbivudine (LdT) plus
peg-interferon (pegIFN) in HBeAg-positive chronic hepatitis B -- very potent
antiviral efficacy but risk of peripheral neuropathy (PN). 45th Annual Meeting
of the European Association for the Study of the Liver (EASL 2010). Vienna,
Austria. April 14-18, 2010. (Abstract).



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富贵数字

在线翻译了， 不是很对的，感觉看了晕晕的