title: A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B.
abstract: Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-alpha, and thymosin-alpha1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-alpha1, 1.6 microg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) > or = 1.5 x upper normal limit, but < or = 10 x upper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P = 0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.
authors.affiliation: Department of Gastroenterology and Hepatology, National University Hospital, Singapore. mdclimsg@nus.edu.sg
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Chun-too
authors.initials: CT
authors.lastname: Wai
authors.forename: Yin Mei
authors.initials: YM
authors.lastname: Lee
authors.forename: Yock Young
authors.initials: YY
authors.lastname: Dan
authors.forename: Dede Selamat
authors.initials: DS
authors.lastname: Sutedja
authors.forename: Aileen
authors.initials: A
authors.lastname: Wee
authors.forename: Shirley
authors.initials: S
authors.lastname: Suresh
authors.forename: Ying Juan
authors.initials: YJ
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Machin
authors.forename: Chee Chian
authors.initials: CC
authors.lastname: Lim
authors.forename: Kwong Ming
authors.initials: KM
authors.lastname: Fock
authors.forename: Evelyn
authors.initials: E
authors.lastname: Koay
authors.forename: Scott
authors.initials: S
authors.lastname: Bowden
authors.forename: Steven
authors.initials: S
authors.lastname: Locarnini
authors.forename: Shamsuddin Mohammed
authors.initials: SM
authors.lastname: Ishaque
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D000077596:Thymalfasin; D013947:Thymosin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D010919:Placebos; D013947:Thymosin; D000077596:Thymalfasin