Hepatology International
DOI: 10.1007/s12072-011-9314-7
Online First™
Original Article
Telbivudine in combination with adefovir versus adefovir monotherapy in
HBeAg-positive, lamivudine-resistant chronic hepatitis B
Sang-Hoon Ahn, Young-Oh Kweon, Seung-Woon Paik, Joo-Hyun Sohn, Kwan-Sik
Lee, Dong Joon Kim, Teerha Piratvisuth, Man Fung Yuen, Anuchit Chutaputti
and You-Chen Chao, et al.
Abstract
Purpose
Lamivudine (LAM) resistance is common on lamivudine monotherapy for chronic
hepatitis B. This study examined the safety and efficacy of telbivudine
(LDT) given with adefovir (ADV) versus ADV monotherapy in patients with
chronic, lamivudine-resistant HBV infection. Methods An open-label, 96 week
study with planned recruitment of 150 HBeAg-positive,
lamivudine-experienced Asian patients with a confirmed YMDD resistance
mutation, randomized 1:1 to receive ADV alone or with LDT. The study was
terminated early due to difficulty in enrolling monotherapy patients. At
termination, 42 patients had received study medication for 8–61 weeks.
Due to incomplete enrolment, summary statistics only were prepared, without
significance testing. Results A total of 42 patients underwent rescue
therapy (switch to ADV or LDT + ADV; n = 21 per group). Median treatment
duration was 48 weeks in both groups. HBV DNA changes from baseline were
greater in the LDT + ADV arm at all time points (Week 48: −7.4 log10 vs.
−4.9 log10 copies/ml), and serum DNA was undetectable (<300 copies/mL) at
week 48 in 38.5% (5/13) on LDT + ADV versus 0% (0/9) on ADV monotherapy Two
patients (9.6%) on ADV monotherapy experienced virologic breakthrough
without evidence of ADV resistance, but none on LDT + ADV; and no confirmed
ADV resistance was observed in any on-treatment sample. HBeAg loss occurred
in three patients on LDT + ADV and one patient on ADV monotherapy through
week 48. Safety profiles were similar between the arms. Conclusion LDT +
ADV combination treatment showed better outcomes against lamivudine
resistant HBV than ADV alone, with a similar safety profile.