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

Abstract

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% 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.