Patrick Marcellin1, Sang Hoon Ahn2, Xiaoli Ma3, Florin A Caruntu4, Won Young Tak5, Magdy Elkashab6, Wan-Long Chuang7, Seng-Gee Lim8, Fehmi Tabak9, Rajiv Mehta10, Joerg Petersen11, Graham R Foster12, Lillian Lou13, Eduardo B Martins14, Phillip Dinh14, Lanjia Lin14, Amoreena Corsa14, Prista Charuworn14, G Mani Subramanian14, Hans Reiser14, Hendrick W Reesink15, Scott Fung16, Simone I Strasser17, Huy Trinh18, Maria Buti19, Giovanni B Gaeta20, Aric J Hui21, George Papatheodoridis22, Robert Flisiak23, Henry L Y Chan24. 1. Service d'Hépatologie, Hôpital Beaujon, University Paris-Diderot, Inserm Centre de Recherche sur l'Inflammation, Clichy, France. 2. Division of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea. 3. Drexel University College of Medicine, Philadelphia, Pennsylvania. 4. National Institute for Infectious Diseases, "Matei Bals", Bucharest, Romania. 5. Kyungpook National University Hospital, Daegu, South Korea. 6. Toronto Liver Center, Toronto, Canada. 7. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 9. University of Istanbul, Cerrahpasa Medical Faculty, Istanbul, Turkey. 10. Liver Clinic, Surat, India. 11. IFI Institute for Interdisciplinary Medicine at the Asklepios Klinik St. George, University of Hamburg, Hamburg, Germany. 12. Queen Mary University of London, London, United Kingdom. 13. Nexus Development, Palo Alto, California. 14. Gilead Sciences Inc, Foster City, California. 15. Academic Medical Center, Amsterdam, The Netherlands. 16. University of Toronto, Department of Medicine, Toronto General Hospital, Toronto, Canada. 17. AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia. 18. San Jose Gastroenterology, San Jose, California. 19. Hepatology Unit, Hospital Universitari Vall d'Hebron and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto Carlos III, Barcelona, Spain. 20. Viral Hepatitis Unit, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy. 21. The Chinese University of Hong Kong, Alice Ho Miu Ling Nethersole Hospital, Hong Kong. 22. Athens University Medical School, "Laiko" General Hospital of Athens, Athens, Greece. 23. Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland. 24. Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. Electronic address: hlychan@cuhk.edu.hk.
Abstract
BACKGROUND & AIMS: Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination oftenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. METHODS: In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. RESULTS: At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. CONCLUSIONS: A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.
RCT Entities:
BACKGROUND & AIMS:Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. METHODS: In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. RESULTS: At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. CONCLUSIONS: A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.
Authors: Norah A Terrault; Anna S F Lok; Brian J McMahon; Kyong-Mi Chang; Jessica P Hwang; Maureen M Jonas; Robert S Brown; Natalie H Bzowej; John B Wong Journal: Hepatology Date: 2018-04 Impact factor: 17.425