Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B

Kin Seng Liem, Margo J H van Campenhout, Qing Xie, Willem Pieter Brouwer, Heng Chi, Xun Qi, Liang Chen, Fehmi Tabak, Bettina E Hansen, Harry L A Janssen, Kin Seng Liem, Margo J H van Campenhout, Qing Xie, Willem Pieter Brouwer, Heng Chi, Xun Qi, Liang Chen, Fehmi Tabak, Bettina E Hansen, Harry L A Janssen

Abstract

Background: Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear.

Aims: To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response.

Methods: Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN.

Results: Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82).

Conclusions: PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).

©2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Combined study design. *Response: HBeAg loss in combination with HBV DNA <200 IU/mL at EOF for the intention‐to‐treat population. **Only for responders. Non‐responders were treated with ETV until EOF. Of the 32 patients who reached response at EOT, 16/25 patients assigned PEG‐IFN add‐on and 2/7 patients assigned ETV monotherapy discontinued treatment after 24 weeks of consolidation therapy. Of these patients, 12/16 vs 2/2 patients allocated to PEG‐IFN add‐on vs ETV monotherapy sustained response at EOF. EOT, end of treatment; EOF, end of follow‐up
Figure 2
Figure 2
Response. *P < 0.05. Of 32 patients who reached combined HBeAg loss and HBV DNA <200 IU/mL at week 48, 18 discontinued treatment after ETV consolidation therapy. EOT, end of treatment; EOF, end of follow‐up
Figure 3
Figure 3
Algorithm for probability of response at end of follow‐up based on HBV DNA and HBsAg at baseline

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