Adding pegylated interferon to entecavir for hepatitis B e antigen–positive chronic hepatitis B: A multicenter randomized trial (ARES study)

Abstract

,15 for the ARES Study Group Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 mg/week) from week 24 to 48 (n 5 85) or to continue ETV monotherapy (n 5 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add-on arm versus 9 of 90 (10%) in the monotherapy arm (P 5 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg-IFN add-on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6-14.0; P 5 0.004). Eleven (13%) of the add-on-treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P 5 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P 5 0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P 5 0.036). Peg-IFN add-on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated. Conclusion: Although the primary endpoint was not reached, 24 weeks of Peg-IFN add-on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogs. (HEPATOLOGY 2015;61:1512-1522

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…130,132,133 The multicentre ARES study demonstrated that a 24-week course of PegIFNa, given to a small group of HBeAg-positive patients who were on ETV therapy for only 24 weeks, can improve the kinetics of HBeAg, HBV DNA and HBsAg, compared to those on ETV monotherapy, but a PegIFNa monotherapy arm was missing. 134 In CHB patients under long-term effective virological remission by NA treatment, PegIFNa can be used as a 'switch to' or 'add-on' strategy. In HBeAg-positive CHB, two recent Chinese studies assessed the efficacy and safety of switching to PegIFNa for patients on long-term effective NA therapy.…”

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

“…This drug, particularly in combination with PEG IFNα2a, have shown good results in HBsAg decline [8] .…”

A hepatitis B- és D-vírus-fertőzés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-től

“…NA plusz peg-IFN add-on kezelés [14] Választható az alábbi esetekben: HBeAg-pozitív, illetve HBeAg-negatív CHB, ha legalább egyéves NA-monoterápiára nem következett be HBeAg-, illetve HBsAg-szerokonverzió -a HBV-DNS-titertől függetlenül -, az NA-kezelés egy évig peg-IFN-nel kombinálható.…”