Z Gastroenterol 2009; 47 - P153
DOI: 10.1055/s-0029-1241403

Two year safety and tolerability of tenofovir disoproxil fumarate (TDF) treatment in HBeAg negative and HBEAG positive patients with chronic hepatitis B (CHB)

P Buggisch 1, M Manns 2, S Mauss 3, T Berg 4, G Teuber 5, J Petersen 1, M Schuchmann 6, S Zeuzem 5, P Marcellin 7, J Heathcote 8, J Sorbel 9, F Rousseau 9
  • 1IFI Institut für Interdisziplinäre Medizin, Hamburg, Germany
  • 2Medizinische Hochschule Hannover, Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
  • 3Gemeinschaftspraxis, Düsseldorf, Germany
  • 4Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Berlin, Germany
  • 5Johann Wolfgang Goethe-Universität, Zentrum für Innere Medizin, Frankfurt am Main, Germany
  • 6Johannes Gutenberg Universität Mainz, I. Medizinische Klinik und Poliklinik, Mainz, Germany
  • 7Universite de Paris, Clichy, France
  • 8University of Toronto, Toronto, Canada
  • 9Gilead Sciences, Durham, United States

Introduction: Tenofovir disoproxil fumarate (TDF) has a well established long term safety profile in HIV-1 infected patients with more than 2 million patient years of exposure. TDF has activity against hepatitis B virus (HBV) and was approved in 2008 for the treatment of CHB.

Goal: To evaluate the safety and tolerability of 2 years of TDF treatment in patients with CHB.

Methods: In the Phase 3 studies 102 and 103, HBeAg negative or HBeAg positive CHB patients were randomized 2:1 to double-blind, once daily TDF 300mg or adefovir dipivoxil (ADV) 10mg. At Week (W) 48, patients with a W48 biopsy continued on open-label (OL) TDF for up to 7 additional years. Included in this W96 analysis are 389 patients who initiated OL TDF and were treated for up to 2 years.

Results: Overall, the following occurred at a low frequency during OL TDF treatment in Year 2: serious AEs (SAEs) (4%), Grade (G) 3 or G4 AEs (5%), AEs considered related to TDF (6%), and AEs resulting in discontinuation (<1%). One death occurred during Year 2 due to cholangiocellular carcinoma. The patient had been diagnosed with severe adrenal gland and lymph node metastases at weeks 40–42. Individual G3 or G4 AEs and SAEs occurred at a frequency of <1%. SAEs considered related to TDF during Year 2 included facial spasm and renal impairment (peak creatinine 1.4mg/dL with improvement to 1.2mg/dL at W96). Three patients discontinued due to AEs: HCC, increased creatinine (peak 1.3mg/dL) and disturbance in attention, fatigue, and dizziness. No patient experienced bone fractures that were considered pathological, related to TDF, or associated with abnormalities in calcium, phosphorus, alkaline phosphatase or renal laboratory parameters. G3–4 laboratory abnormalities occurring in >1% of patients during OL TDF included glucosuria (3%), elevated serum amylase (2%) and elevated prothrombin time (2%). All patients with glucosuria had elevated serum glucose and most were diabetics. During OL TDF, no TDF patient had a confirmed decrease in creatinine clearance <50 mL/min or confirmed increase in creatinine ≥0.5mg/dL.

Conclusion: TDF was well tolerated for 2 years in patients with CHB and the safety profile was consistent with what has been observed in HIV-infected patients.