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).
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.



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.



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.



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.



NCT01532843.
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Heng
H
Chi
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Bettina E
BE
Hansen
Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
Simin
S
Guo
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai, China.
Ning Ping
NP
Zhang
Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Xun
X
Qi
Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Liang
L
Chen
Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
Qing
Q
Guo
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Pauline
P
Arends
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai, China.
Ji-Yao
JY
Wang
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Elke
E
Verhey
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Robert J
RJ
de Knegt
Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
Qing
Q
Xie
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.|Toronto Centre for Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Canada.
Harry L A
HLA
Janssen
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D002681:China; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; C417083:peginterferon alfa-2b
Antiviral therapy; HBeAg seroconversion; combination therapy; interferon naive.