Hepatitis B Surface Antigen Loss with Tenofovir Disoproxil Fumarate Plus Peginterferon Alfa-2a: Week 120 Analysis

Abstract

Background and AimsHepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120.MethodsIn an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed.ResultsRates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P < 0.001 for both) or group D (HBsAg loss: P = 0.002; HBsAg seroconversion: P < 0.001).ConclusionsThe results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.Electronic supplementary materialThe online version of this article (10.1007/s10620-018-5251-9) contains supplementary material, which is available to authorized users.

Effects of pegylated interferon‐α based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B

“…In Study 149, the HBeAg seroconversion rate was higher in HBeAg‐positive patients treated with peg‐IFN‐α plus TDF for 48 weeks than in those treated with TDF alone (25.0% vs 12.8%, respectively; P = 0.025) at week 72 (24 weeks after peg‐IFN‐α cessation). The cumulative rate of HBsAg loss at week 120 of follow‐up was significantly higher in patients (including both HBeAg‐positive and HBeAg‐negative patients) receiving combination therapy than in those receiving peg‐IFN‐α or TDF alone (10.4% vs 3.5% vs 0%, respectively; P < 0.001 and P = 0.002) …”

“…At week 72 of follow‐up when patients in the peg‐IFN‐α group had discontinued therapy for 24 weeks but patients in the TDF group were still on‐treatment, HBsAg loss was observed in 3.8% and 0% of patients, respectively. In an extended follow‐up analysis of Study 149 up to week 120, HBsAg loss was observed in 3.5% and 0% of patients (including both HBeAg‐positive and HBeAg‐negative patients) treated with peg‐IFN‐α and TDF monotherapy, respectively …”

“…In an extended follow-up analysis of Study 149 up to week 120, HBsAg loss was observed in 3.5% and 0% of patients (including both HBeAg-positive and HBeAg-negative patients) treated with peg-IFNα and TDF monotherapy, respectively. 14 The HBeAg seroconversion rate has continued to be relatively high during long-term follow-up after discontinuation of peg-IFNα monotherapy. In the NEPTUNE study, 15 which was conducted mainly in Asian patients, those treated with peg-IFNα monotherapy achieved an HBeAg seroconversion rate of 48% at 5 years after treatment discontinuation.…”

Abstracts

“…A decline in HBsAg at week 12 or 24 of treatment was associated with HBsAg loss at week 72, while a decrease in HBsAg >3.5 log 10 IU/mL at week 24 identified HBsAg loss at week 72 in patients who completed a 48‐week course of Peg‐IFN+TDF (PPV = 85% and NPV = 99%) 3 . Follow‐up data at week 120 confirm the increased rate of HBsAg loss in patients treated with Peg‐IFN+TDF compared to those receiving either monotherapy (10.4% vs 3.5% in group B and D vs 0% in group C) 4 …”

Roadmap to functional cure of chronic hepatitis B: An expert consensus

“…A recent randomized controlled trial evaluating HBsAg loss in both HBeAg‐positive and HBeAg‐negative treatment‐naive patients showed that 48 weeks of combination therapy with TDF and Peg‐IFN led to a greater on‐treatment HBsAg decline at the end of treatment and a higher rate of HBsAg loss (9.1%) at 24 weeks post‐treatment than 16 weeks of combination therapy or either monotherapy alone, particularly in genotype A patients . At week 120, 10.4% of patients treated with combination therapy with TDF and Peg‐IFN for 48 weeks lost HBsAg . A recent study in 26 patients with HBV genotype C infection administered both ETV and Peg‐IFN simultaneously for 48 weeks showed that the 5‐year cumulative rate of HBsAg loss after the completion of combination therapy was 15% …”