Patrick Marcellin1, Karsten Wursthorn2, Heiner Wedemeyer2, Wan-Long Chuang3, George Lau4, Claudio Avila5, Cheng-Yuan Peng6, Edward Gane7, Seng Gee Lim8, Hugo Fainboim9, Graham R Foster10, Rifaat Safadi11, Mario Rizzetto12, Michael Manns2, Weibin Bao13, Aldo Trylesinski5, Nikolai Naoumov5. 1. Service d'Hépatologie, INSERM-CRB3, Hôpital Beaujon, Clichy, France. Electronic address: patrick.marcellin@bjn.aphp.fr. 2. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. 3. Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Humanity and Health GI and Liver Clinic, Hong Kong Special Administrative Region. 5. Novartis Pharma AG, Basel, Switzerland. 6. School of Medicine, China Medical University, and Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 7. New Zealand Liver Unit, Auckland City Hospital, Auckland, New Zealand. 8. Department of Gastroenterology and Hepatology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore. 9. Unidad 4, Hepatopatias Infecciosas, Hospital Francisco Muñiz, AAEEH, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. 10. Queen Mary University of London, The Liver Unit, Blizard Institute of Cellular and Molecular Science, Barts and The London School of Medicine, The Royal London Hospital, London, UK. 11. Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 12. Department of Gastroenterology, University of Turin, Turin, Italy. 13. Novartis Pharmaceuticals, East Hanover, NJ, USA.
Abstract
BACKGROUND & AIMS: This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. METHODS: This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group. RESULTS: Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p<0.0001 for combination therapy vs. PegIFN). CONCLUSIONS: Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used.
RCT Entities:
BACKGROUND & AIMS: This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. METHODS: This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group. RESULTS: Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p<0.0001 for combination therapy vs. PegIFN). CONCLUSIONS: Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used.
Authors: S K Sarin; M Kumar; G K Lau; Z Abbas; H L Y Chan; C J Chen; D S Chen; H L Chen; P J Chen; R N Chien; A K Dokmeci; Ed Gane; J L Hou; W Jafri; J Jia; J H Kim; C L Lai; H C Lee; S G Lim; C J Liu; S Locarnini; M Al Mahtab; R Mohamed; M Omata; J Park; T Piratvisuth; B C Sharma; J Sollano; F S Wang; L Wei; M F Yuen; S S Zheng; J H Kao Journal: Hepatol Int Date: 2015-11-13 Impact factor: 6.047