Clinical

Telbivudine effective treatment for chronic hepatitis B

Last Updated: 2007-12-19 17:00:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Telbivudine is more effective than lamivudine in reducing viral load in patients with chronic hepatitis B (HBV), according to findings from a multinational, phase 3 trial reported in the New England Journal of Medicine for December 20. Drug resistance is also far less of a problem with telbivudine.

Multiple agents are approved for treatment of chronic hepatitis B. A primary treatment goal, lead author Dr. Ching-Lung Lai and associates note, is long-lasting HBV suppression, important in preventing progression to end-stage complications such as cirrhosis and hepatocellular carcinoma.

Dr. Lai, at Queen Mary Hospital in Hong Kong, and associates recruited 1367 patients (921 hepatitis B e antigen (HBeAg)-positive and 446 HBeAg-negative). Patients were randomized to treatment with telbivudine 600 mg daily or lamivudine 100 mg daily for 52 weeks. Serum HBV DNA levels were greater than 6 log10 copies/mL at baseline.

A therapeutic response was defined as "a reduction in the serum HBV DNA level to fewer than 5 log10 copies per milliliter...coupled with either normalization of the alanine aminotransferase level or loss of detectable HBeAg."

At week 52, a significantly greater proportion of HBeAg-positive patients treated with telbivudine had a therapeutic response (75.3% versus 67.0%, p = .005). Response rates to the two drugs were similar in HBeAg-negative patients (75.2% versus 77.2%, p = .62).

In both groups of patients, the investigators report, telbivudine was superior to lamivudine in reducing viral load. The difference in serum HBV DNA was evident by 8 to 12 weeks.

Viral breakthrough with treatment-emergent resistance mutations occurred less frequently with telbivudine (maximum 5.0% versus 11%, p < .001).

Dr. Lai's team comments that, as with all nucleoside or nucleotide therapies for HBV, cumulative resistance to telbivudine is likely to increase as therapy is extended.

The investigators conclude: "Future studies of patients with suboptimal responses may determine whether early treatment modification, using drugs with complementary resistance profiles, can improve subsequent outcomes."

N Engl J Med 2007;357:2576-2588.