Switch to Lamivudine Not as Effective as Staying on Entecavir

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Switch to Lamivudine Not as Effective as Staying on Entecavir

SUMMARY

Hepatitis B patients who switch to cheaper lamivudine (Epivir-HBV) after

achieving undetectable HBV viral load and normal ALT on entecavir (Baraclude)

are more likely to experience viral rebound.

By Learned

Hepatitis B Virus

Lamivudine was the first oral drug approved to treat chronic hepatitis B virus

(HBV) infection, and it has proved to be effective in slowing disease

progression and reducing the risk of liver decompensation and liver cancer.

Unfortunately, taking lamivudine over the long term results in high rates of

drug resistance -- up to 76% after 8 years of treatment. In contrast, the newer

drug entecavir has a very low resistance rate -- only about 1% after 5 years of

monotherapy. This makes lamivudine less than ideal as a treatment for chronic

hepatitis B.

Recognizing that early suppression of HBV predicts a positive outcome over time,

including fewer drug-resistance mutations, Fung and colleagues from the

University of Hong Kong hypothesized that people with sustained undetectable HBV

viral load while on entecavir might continue to do well if they switch to

lamivudine, a weaker but less expensive drug. The lower cost of lamivudine --

especially in countries with large numbers of people with hepatitis B -- may

have been a primary rationale for this study.

As described in the April 2011 issue of Hepatology, the researchers designed a

2-arm study to evaluate whether switching to lamivudine might provide optimal

HBV suppression after patients took entecavir for 6 or more months. One half of

the study participants remained on 0.5 mg/day entecavir for 96 weeks while the

other half (with a few exceptions) switched to 100 mg/day lamivudine monotherapy

for the duration of the study.

There were 50 participants in the study, largely men (72%). About 20% were

hepatitis B " e " antigen (HBeAg) positive. All had been treated with 0.5 mg/day

entecavir for 6 to 25 months prior to study entry and had normal alanine

aminotransferase (ALT) and undetectable HBV DNA (< 60 copies/mL). There were 6

participants with compensated liver cirrhosis at study entry. Patients with

elevated ALT or detectable HBV viral load were excluded from the trial. Other

exclusion criteria included evidence of liver cancer and a history of

decompensated cirrhosis.

Participants who were randomly assigned to take lamivudine switched back to

entecavir for the remainder of the study if they showed was evidence of HBV

virological rebound. If they developed lamivudine resistance, they were treated

with a combination of lamivudine and adefovir (Hepsera).

Results

At 96 weeks, all 25 (100%) of participants in the entecavir arm still had

undetectable HBV viral load.

Participants in the lamivudine arm did not fare as well: 6 out of 25 (24%)

experienced HBV viral rebound.

There were no significant differences in the time on entecavir or pre-treatment

viral load between patients with and without virological rebound after switching

to lamivudine.

No ALT elevation was seen in any participants in either arm of the trial

through 96 weeks.

Among the participants taking lamivudine who experienced HBV rebound, 3

achieved undetectable viral load again after switching back to entecavir.

No new symptoms or serious adverse events occurred throughout 96 weeks.

3 participants (12%) in the lamivudine arm developed lamivudine resistance,

while none of the participants in the entecavir arm developed resistance

mutations.

The researchers discussed several limitations of their study: 1) The length of

treatment with entecavir was not controlled, since patients had been taking

entecavir for at least 6 months -- but often much longer -- before joining the

study; 2) Most of the study participants were HBeAg negative, and the results

might vary if they had been HBeAg positive; and 3) Neither hepatitis B genotype

nor rates of achieving undetectable HBV viral load were determined, so their

effects on virological rebound could not be assessed.

Based on their findings, the researchers concluded, " Prior optimal viral

suppression with entecavir did not confer any significant advantage in patients

who switched to lamivudine. " In fact, they continued, switching from entecavir

to lamivudine " resulted in a virological rebound rate of 24% and a resistance

rate of 12% after 96 weeks [2 years]. "

Investigator affiliations: Hepatitis and Liver Clinic and State Key Laboratory

for Liver Research, Queen Hospital, Hong Kong.

5/6/11

Reference

Fung, Ching-Lung Lai, Yuen, et al. Randomized trial of lamivudine

versus entecavir in entecavir-treated patients with undetectable hepatitis B

virus DNA: Outcome at 2 Years. Hepatology 63(4): 1148-1153 (abstract). April

2011.