1Service d'Hépatologie, INSERM-CRB3, Hôpital Beaujon, Clichy, France. Electronic address: email@example.com.
2Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
3Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
4Humanity and Health GI and Liver Clinic, Hong Kong, SAR.
5Novartis Pharma AG, Basel, Switzerland.
6School of Medicine, China Medical University, and Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
7New Zealand Liver Unit, Auckland City Hospital, Auckland, New Zealand.
8Department of Gastroenterology and Hepatology, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
9Unidad 4, Hepatopatias Infecciosas, Hospital Francisco Muñiz, AAEEH, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
10Queen 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.
11Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
12Department of Gastroenterology, University of Turin, Turin, Italy.
13Novartis Pharmaceuticals, East Hanover, New Jersey, USA.
BACKGROUND AND 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 AND METHODS:
This was a randomized, open-label, multicenter 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.
Of the 159 patients randomized from 300 planned (50 to combination therapy, 55 to telbivudine, 54 to PegIFN), 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 population, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, CK 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).
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.