PegInterferon + Entecavir - Results from a global trial
干扰素和恩替卡韦联合的临床试验结果
肝胆速递：有助于HBe转阴及HBsAg清除
Nederlandse Vereniging voor Hepatologie (klinisch)
ADDING PEGINTERFERON ALFA-2A TO ENTECAVIR INCREASES HBSAG DECLINE AND HBEAG CLEARANCE – FIRST RESULTS FROM A GLOBAL RANDOMIZED TRIAL (ARES STUDY)
M.J. Sonneveld1, Q. Xie2, N.P. Zhang3, Q. Zhang4, F. Tabak5, A. Streinu6, J.-Y. Wang3, R. Idilman7, A. de Niet8, M. Diculescu9, A.J. van Vuuren1, E. Verhey1, B.E. Hansen1,10, H.L.A. Janssen1
Departments of 1Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; 2Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China; 3Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 4Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 5Department of Infectious Diseases, Cerrahpasa Medical School, Istanbul, Turkey; 6National Institute of Infectious Disease, Bucharest, Romania; 7Gastroenterology and Hepatology, University of Ankara, Ankara, Turkey; 8Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands; 9Gastroenterology, Fundeni Cinical Institute, Bucharest, Romania; 10Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands;
Background & aims. Entecavir (ETV) is a potent inhibitor of viral replication in HBeAg-positive chronic hepatitis B (CHB) patients, but serological response is infrequently achieved and indefinite therapy should therefore be anticipated in the majority of patients. Addition of peginterferon (PEG-IFN) to ETV may increase serological response rates.
Methods. In this investigator-initiated randomized controlled trial 184 HBeAg-positive patients with compensated liver disease were enrolled at 15 sites in Europe and China and allocated to either ETV 0.5mg daily alone for 48 weeks or a 24 week addition of PEG-IFN alfa-2a 180 ug weekly after 24 weeks of ETV monotherapy. Response (HBeAg loss with HBV DNA <200 IU/mL) was assessed at week 48, and responders were allowed to discontinue treatment after 24 weeks consolidation treatment (week 72), with subsequent off-treatment follow-up until week 96. Results at week 48 are presented here.
Results. 177 patients received at least one dose of allocated treatment, 93 ETV alone and 84 ETV with PEG-IFN add-on. Sixty-one percent of patients were of Asian ethnicity and all major HBV genotypes were present (A/B/C/D in 7/19/42/32%). A total of 160 patients had reached week 48 by June 2012, and the remaining patients will do so within 2 months. Patients were comparable with regard to important baseline characteristics, except for HBsAg which was higher in patients receiving combination therapy (4.28 versus 4.03 log IU/mL, p=0.05). Response, as well as HBeAg loss alone, was achieved in 18% of patients who received PEG-IFN add-on, compared to 8% of patients treated with ETV alone (p=0.07). PEG-IFN add-on resulted in more decline of HBV DNA (6.33 versus 5.91 log IU/mL, p=0.05), HBeAg (1.99 versus 1.56 log IU/mL, p=0.01) and HBsAg (0.84 versus 0.32 log IU/mL, p<0.001) at week 48. Only one patient (who received PEG-IFN add-on) had clearance of HBsAg at week 48. After adjustment for the differences in baseline HBsAg levels, addition of PEG-IFN was independently associated with response at week 48 (adjusted odds ratio: 3.63, 95% CI: 1.24 – 10.7, p=0.01). Add-on PEG-IFN was well-tolerated and no relevant safety concerns were raised.
Conclusion. A 24 week add-on of PEG-IFN treatment increases HBsAg decline and clearance of HBeAg and may therefore improve the chances of finite treatment in HBeAg-positive CHB patients treated with ETV.
