TENOFOVIR DF (TDF) IS SAFE AND WELL TOLERATED IN CHRONIC HEPATITIS B (CHB) PATIENTS WITH PRE-EXISTING MILD RENAL IMPAIRMENT
S. Fung1*, P. Kwan2, A. Horban3, M. Pelemis4, P. Husa5, H.W. Hann6, J. Flaherty7, B. Massetto7, P. Dinh7, J. Custodio7, G.M. Subramanian7, M. Fabri8, E. Gane9
1University of Toronto, Toronto, ON, 2University of British Columbia, Vancouver, BC, Canada, 3Medical University of Warsaw, Warsaw, Poland, 4Clinic for Infectious and Tropical Diseases, Clinical Center Serbia, Belgrade, Serbia, 5Masaryk University Brno, Brno, Czech Republic, 6Thomas Jefferson University, Philadelphia, PA, 7Gilead Sciences, Foster City, CA, USA, 8Clinic for Infectious Diseases, Novi Sad, Serbia, 9Auckland General Hospital, Auckland, New Zealand. *[email protected]
Background and aims: TDF has demonstrated sustained HBV suppression and a favorable safety profile through 6 years; however, data are limited in CHB patients with mild renal impairment (MRI) as they are excluded from most trials. MRI patients (CrCL 50 - < 80 mL/min by Cockroft-Gault) were included in a prospective, randomized, double-blind trial of TDF vs. FTC/TDF in lamivudine-resistant patients (Study 121) wherein no differences were observed in efficacy or safety between treatments (Fung S. AASLD 2012, #20).
Methods: Post-hoc analysis of Study 121 which compared MRI patients (74/280; 26%) and normal renal function (NRF; CrCL ≥80 mL/min) patients (206/280; 74%). Safety, including bone mineral density (BMD) monitoring by DXA, pharmacokinetics (PK; MRI patients only), and efficacy were assessed over 96 weeks.
Results: At baseline (BL), mean (SD) CrCL was 67 (9) mL/min for the MRI group and 104 (18) mL/min for the NRF group. Both groups (MRI vs. NRF) were well matched except: mean age 58 vs. 43 yrs (p< 0.001), males 59% vs. 81% (p< 0.001), prior IFN 18% vs. 32% (p=0.015), and prior ADV 14% vs. 25% (p=0.044). Tenofovir (TFV) PK parameters (AUCτ, Cmax, Tmax) in MRI were comparable to historical data in NRF, and there was no correlation between steady-state TFV exposures (AUCτ) and BL CrCL. TDF was well tolerated overall; 3 patients (1.1%) discontinued the study early for an AE (2-MRI and 1-NRF). No patients had a confirmed increase in serum creatinine of ≥0.5 mg/dL, and 1% (2-NRF) had transient PO4 < 2 mg/dL. Nine MRI patients had CLCr < 50 mL/min (pre-treatment range: 49-61 mL/min) that stabilized with dose adjustment. No differences were observed in % change in spine or hip BMD over 96 weeks, and no clinically relevant bone loss was noted in either group. At Week 96 there was no significant difference (missing=failure) in % with HBV DNA < 400 copies/mL, or rates of ALT normalization or HBeAg loss/seroconversion.
Conclusions: The safety, PK, and efficacy of patients with MRI receiving TDF were similar to NRF patients; in MRI patients there was no evidence of increased risk for renal- or bone-related complications.
Assigned speakers:
Dr. Scott Fung, University of Toronto , Toronto , Canada
Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area 作者: StephenW 时间: 2013-4-19 20:05