S-104 : Antiviral activity and safety of ADEFOVIL compared with HEPSERA in hepatitis B

Background: Antiviral resistance is an important issue determining success or failure of the management of hepatitis B. Adefovir dipivoxil has been widely used as a combination to nucleoside analogues (NAs) in cases of resistance. The present study aimed toinvestigate the antiviral activity and safety of ADEFOVIL compared with HEPSERA. Methods: In this randomized, open-label, multi-center study, the inclusion criteria were as follows: use of NA plus HEPSERA for ≥6 months before enrollment; compensated liverdisease. Exclusion criteria were coinfection with HCV or HIV, malignancy, alcohol dependence, azotemia and pregnancy. Between December 2011 and April 2014, 123 patients were randomly assigned to either ADEVOFIL or HEPSERA, and received one of the study drugs plus NAs for 48 weeks. The primary endpoint was noninferiority of virological response of ADEFOVIL vs.HEPSERA. Results: After withdrawal of 18 patients (due to refusal), remaining 105 patients were included in the analysis (54 in ADEFOVIL (A) group and 51in HEPSERA (H) group). Baseline characteristics (age, sex, HBeAg positivity, presence of cirrhosis) showed no significant difference between the two groups. Proportions of lamivudine (LAM): telbivudine (LdT): entecavir (ETV) were 16.7%: 44.4%: 38.9% (A group) vs. 25.5%: 47.1%: 27.5% (H group). (p＝0.360) Baseline HBV DNA were ＜20 IU/mL (＜20-19,700) in A group vs. ＜20 IU/mL (＜20-17,700) in H group. (p＝0.612) Baseline ALT were 24.5 IU/L (A group) vs. 23 IU/L (H group). (p＝0.629) Changes in HBV DNA (baseline-week 48) were 0.0 IU/mL (interquartile range (IQR), 0-50) in A group vs. 0.0 IU/mL (IQR, 0-81) in H group. (p＝0.507) Undetectable HBV DNA at week 48 was achieved in 50.0% in A group vs. 49.0% in H group. (p＝0.813) Normal ALT were observed in 74.1% of A group vs. 72.5% of H group at week 48. (p＝0.631) Adverse events (AEs) were observed in 25.9% in A group vs. 21.6% in H group; most AEs were mild to moderate. Conclusions: Coadministration of ADEFOVIL with NAs showed equivalent antiviral efficacy and favorable profile of adverse events compared with HEPSERA. Considering its lower expense, ADEFOVIL could be a cost-effective alternative of HEPSERA in CHB patients with resistance to NAs.