Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial

Abstract

Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log 10 versus 5.5 log 10 , P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P ‫؍‬ 0.007), therapeutic response (85% versus 62%, P ‫؍‬ 0.001), and HBeAg loss (31% versus 20%, P ‫؍‬ 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n ‫؍‬ 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. Conclusion: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance. (

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

“…HBeAg seroconversion rates as high as 25% have been reported at 1 year of telbivudine treatment in Asian patients with HBeAg-positive CHB [52]. At 2 years of telbivudine and entecavir treatment, HBeAg seroconversion rates are comparable with those achieved at 24 weeks after a 48-week course of PegIFN in patients with HBeAgpositive CHB [21,23,55].…”

“…The GLOBE study, conducted in 20 countries, compared these two antiviral agents in 1,367 patients (921 HBeAg positive) [22]. A similarly designed study was conducted in China and enrolled 332 patients (290 HBeAg positive) [52]. The HBeAg-positive patients were eligible for discontinuation of therapy if they had received antiviral treatment for more than 1 year and had HBV-DNA levels of \5 log 10 copies/ml (2 9 4 log 10 IU/ ml), with HBeAg loss maintained on treatment for 24 weeks or more.…”

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…For patients with fulminant disease, where a rapid fall in HBV DNA is desirable, a balance has to be found between the need for antivirals, the potential for drug toxicity, and the risk of selecting HBV and HIV drug resistance. Telbivudine in the short term is thought to be safe [145] and, although HBV resistance is likely, probably will not interfere with future ART. The addition of adefovir may theoretically improve efficacy and reduce the risk of telbivudine resistance, although there is no research evidence for this.…”

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“…The second year of the GLOBE trial reported viral breakthroughassociated resistance rates of 25% and 11% in HBeAg-positive and HBeAg-negative patients, respectively (47). In 2008, Hou et al (58) compared LtD efficacy with LAM in CHB HBeAg-positive Chinese patients and reported 7.5% and 14.7% 1-year resistance rates in LtD-and LAM-treated groups, respectively. Recently, comparing ETV and LtD anti-viral efficacy in 151 treatment-naïve patients with HBV-related cirrhosis, a significantly higher rate of resistance was found after 2 years of treatment in patients treated with LtD compared to those treated with ETV (27.3% vs. 0%; p=0.0001) (49).…”