Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t) ide Analogue: A Randomized, Controlled Trial (PEGON)

Background. We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t) ide analogue (NA) therapy, compared with continued NA monotherapy. Methods. This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for > 12 months and had an HBV DNA load of < 2000 IU/mL. Patients were randomly assigned in a 1: 1 ratio to 48 weeks of peginterferon add-on therapy (n = 39) or continued NA monotherapy (n = 38). Response (defined as HBeAg seroconversion with an HBV DNA load of < 200 IU/mL) was assessed at week 48, with responders discontinuing NA therapy at week 72. Results. The primary end point (response at week 96) was achieved in 18% of patients who were assigned peginterferon add-on therapy versus 8% of patients assigned NA monotherapy (P =.31). Among 58 interferon-naive patients, add-on therapy led to a greater frequency of HBeAg seroconversion (30% vs 7%; P =.034) and response (26% vs 7%; P =.068) at week 96, compared with monotherapy. Among 8 responders at week 48 who discontinued NA therapy at week 72, 6 patients (75%) maintained a response until week 96 (4 of 6 [67%] in the add-on therapy group vs 2 of 2 [100%] in the monotherapy group; P = 1.00). Adverse events were mainly related to peginterferon. Conclusion. The primary end point was negative, but peginterferon add-on therapy appeared to result in a greater frequency of HBeAg seroconversion, compared with NA monotherapy, in interferon-naive patients receiving NA therapy.