Telbivudine combination with adefovir versus adefovir monotherapy in HBeAg-positive chronic hepatitis B (CHB) patients with lamivudine resistance

Abstract

Background/Aims: A large proportion of patients fail lamivudine treatment and guidelines recommend switching to nucleotides or add-on therapy. The aim of this report is to evaluate the efficacy and safety of the switch to adefovir (ADV) monotherapy versus telbivudine (LDT) plus adefovir in CHB patients with confirmed YMDD mutation with prior lamivudine treatment. Methods: 150 HBeAg positive patients were planned to be included into an open label randomized 96-week trial evaluating ADV versus ADV + LDT. The study was terminated early due to difficulties enrolling patients into the ADV monotherapy arm. However, 42 patients were randomized 1:1 (91% Korean). Results: Median treatment duration was 48 weeks and 20 patients per arm completed 48 weeks of treatment. HBV DNA decline at week 24 was higher in the combination arm versus ADV monotherapy arm: -6.7 versus -5.0 log10 copies/ml (baseline ADV + LDT:10.3; ADV:10.1 log10 copies/ml). At week 48, HBV DNA decline by -7.4 (ADV + LDT) and -4.9 (ADV) log10 copies/ml, with 38.5% (5/13) and 0% (0/9) of patients, respectively, achieving undetectable HBV DNA (300 copies/ml). Virologic breakthrough occurred in 0% (0/21) of ADV + LDT and 9.6% (2/21) of ADV patients. HBeAg loss was achieved in one patient per arm at week 24 and in 23.1% (3/13) and 0% (0/9) at week 48 in the ADV+LDT versus ADV groups. The safety profile was similar in both treatment arms with 16 AEs reported per group. ALT flares (AASLD criteria) occurred in one patient per arm, increased creatine phosphokinase was reported in 3/21 patients ADV + LDT and 1/21 ADV arm, but all were grade 1/2. One case of musculoskeletal pain and parasthesia each occurred in the combination arm. Conclusion: In these 42 patients with established YMDD resistance on lamivudine treatment, the switch to the combination of telbivudine and adefovir showed better outcomes compared with adefovir alone, and both had a similar safety profile.