Randomised clinical trial: the benefit of combination therapy with adefovir and lamivudine for chronic hepatitis B

Abstract

Background: Combination antiviral therapy holds the promise of increasing response rates while decreasing antiviral resistance, but has yet to be shown to be beneficial or necessary in chronic hepatitis B.

Aim: To evaluate the benefit of combination therapy with adefovir and lamivudine versus adefovir alone in maintaining virological, biochemical and histological responses.

Methods: Patients with chronic hepatitis B with and without previous lamivudine therapy were randomised to receive adefovir alone (10 mg/daily) or adefovir and lamivudine (100 mg/daily) for up to 192 weeks. Study endpoints were (i) maintained virological (HBV DNA <500 copies/mL), biochemical and histological response, (ii) loss of HBeAg and (iii) loss of HBsAg.

Results: A total of 41 patients were enrolled, including 31 HBeAg -positive and 31 treatment-naïve subjects. 30 patients remained on assigned therapy at 192 weeks. The percentage of patients achieving a combined maintained response was higher in the combination than the monotherapy arm, both at week 48 (59% vs. 26%, P = 0.06) and 192 (68% vs. 31%, P = 0.03). At week 192, 76% of the combination vs. 36% of the monotherapy group had loss of HBeAg (P = 0.03). One patient receiving adefovir cleared HBsAg. Adefovir resistance developed in 6 of 19 (32%) monotherapy but none of 22 combination treated patients (P = 0.03).

Conclusions: Extended combination therapy with lamivudine and adefovir is associated with a high rate of long-term virological and biochemical response. Adefovir monotherapy appears to be less effective mainly because of poor initial response and the ultimate development of antiviral resistance (www.Clinical. Trials.gov NCT00023309).

Published 2012. This article is a US Government work and is in the public domain in the USA.

Figures

Figure 1 ∣

Time to loss of HBeAg by treatment group using life-table analysis.

Figure 2 ∣

(a) Mean histology activity index scores among patients on combination therapy with lamivudine and adefovir (Lam & Adv) vs. adefovir monotherapy (Adv) at baseline, 48 weeks and 192 weeks. (b) Mean Ishak fibrosis scores among patients on combination therapy with lamivudine and adefovir (Lam & Adv) vs. adefovir monotherapy (Adv) at baseline, 48 weeks and 192 weeks.

Figure 3 ∣

(a) Combined maintain response after 48 weeks by treatment group using life-table analysis. (b) Absence of treatment failure after 48 weeks by treatment group using life-table analysis.