title: Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy.
abstract: OBJECTIVE
  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.affiliation: Service d'Hépatologie, INSERM-CRB3, Hôpital Beaujon, Clichy, France. Electronic address: patrick.marcellin@bjn.aphp.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Wursthorn
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Humanity and Health GI and Liver Clinic, Hong Kong Special Administrative Region.
authors.forename: George
authors.initials: G
authors.lastname: Lau
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Avila
authors.affiliation: School of Medicine, China Medical University, and Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: New Zealand Liver Unit, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.affiliation: Department of Gastroenterology and Hepatology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Unidad 4, Hepatopatias Infecciosas, Hospital Francisco Muñiz, AAEEH, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fainboim
authors.affiliation: 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.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Rifaat
authors.initials: R
authors.lastname: Safadi
authors.affiliation: Department of Gastroenterology, University of Turin, Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Weibin
authors.initials: W
authors.lastname: Bao
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Aldo
authors.initials: A
authors.lastname: Trylesinski
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Naoumov
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D004279:DNA, Viral / Q000032:analysis; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D014943:Global Health; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics; D000077712:Telbivudine; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000077712:Telbivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D013936:Thymidine
keywords: Hepatitis B virus; Hepatitis surface antigen; Nucleoside analogue; Pegylated interferon; Telbivudine