1Shanghai Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai, China.
2Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi Province, China.
3The First Affiliated Hospital of Zhengzhou University, Henan, China.
4Shanghai Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
5The First Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
6Beijing Ditan Hospital, Beijing, China.
7People's Liberation Army 85 Hospital, Shanghai, China.
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
9Roche Pharmaceuticals Ltd, Shanghai, China.
Treatment with peginterferon alfa-2a (40KD) results in hepatitis B 'e' antigen (HBeAg) seroconversion 6 months post-treatment in up to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the efficacy of a novel combination of peginterferon alfa-2a and entecavir (ETV), a potent nucleoside analog.
In total, 218 treatment-naive Chinese HBeAg-positive patients were randomized to peginterferon alfa-2a (180 µg/week) for 48 weeks, either as monotherapy (n=72), or with 24 weeks of ETV (0.5 mg/daily) added at week 13 (ETV add-on, n=73), or pretreatment with a 24-week course of ETV, starting peginterferon alfa-2a at week 21 (ETV pretreatment, n=73). The primary endpoint was reduction in quantitative HBeAg from baseline to 24 weeks post-treatment.
Significant reductions in HBeAg from baseline were achieved in all treatment groups 24 weeks post-treatment; reductions were comparable across treatment arms (log10PEIU/mL: monotherapy: -1.4±1.8, ETV add-on: -1.6±1.8, ETV pretreatment: -1.3±1.7). Rates of HBeAg seroconversion were similar across treatment groups post-treatment (monotherapy: 22 [31%], ETV add-on: 18 [25%], ETV pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus DNA were achieved with ETV add-on on-treatment, but were not sustained post-treatment. Safety profiles were comparable between treatment groups; adverse events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 (81%) ETV pretreatment patients.
Neither ETV add-on nor ETV pretreatment demonstrated superiority compared with 48 weeks of peginterferon alfa-2a monotherapy. The optimal treatment strategy using nucleos(t)ide analogs and peginterferon alfa-2a remains to be determined.