Phase Iib Extended-Treatment Trial of Telbivudine (LdT) Vs Lamivudine Vs Combination Treatment in Hepatitis B Patients: Two-Year Results

Abstract

Background: In a 1-year Phase IIb trial, telbivudine (LdT) treatment produced significantly greater antiviral effects and ALT normalization than standard lamivudine monotherapy in HBeAg-positive patients with chronic hepatitis B (Lai AASLD2003). The present follow-on study was designed to gain longer-term data on the comparative efficacy and safety of LdT vs lamivudine in patients who completed the previous trial. Methods: Patients (pts) completing the earlier trial were offered continuing treatment according to their previous treatment type: (a) pts previously treated with lamivudine continued on lamivudine (100 mg/d); (b) pts previously treated with LdT monotherapy (400 or 600 mg/d) continued on LdT 600 mg/d; and (c) pts previously treated with a combination treatment (LdT 400 or 600 mg/d plus lamivudine) continued on combination treatment (LdT 600 mg/d plus lamivudine 100 mg/d). Here we report efficacy and safety observations after 1 year of additional treatment, comprising 2 years of continuous treatment with these 3 types of anti-HBV treatment. Results: 90 of 99 pts (90%) who completed the previous study enrolled in this extension study. Overall tolerance of all 3 treatment regimens remained satisfactory. After 96 weeks of continuous treatment, HBV DNA suppression remained substantially greater with LdT compared to lamivudine. Mean 2-year serum HBV DNA reductions (log10 copies/ml) from pretreatment baseline were 5.2 for LdT vs 3.9 for lamivudine, and HBV DNA was nondetectable by COBAS PCR assay in 71% of LdT recipients vs 32 % of lamivudine recipients (p 0.05). ALT normalization at 2 yrs remained markedly greater for LdT recipients vs lamivudine recipients (81% vs 47%, p 0.05), and HBeAg seroconversion was higher for LdT recipients (38% vs 21%, p ns). Treatment failure (viral breakthrough with elevated ALT) was significantly lower for LdT vs lamivudine (4.5% vs. 21.1%, p 0.05). HBV DNA response in the first 6 months of treatment predicted longer-term efficacy outcomes at 2 years. As in the initial trial, in year 2 the combination regimen appeared proportionally better than lamivudine on all efficacy endpoints but was not better than LdT alone on any endpoint. Conclusions: Continuous telbivudine treatment for 2 years doubled the HBV DNA clearance rate and nearly doubled the ALT normalization rate compared to lamivudine, with proportionally greater HBeAg seroconversion and a much lower resistance-related treatment failure rate.