EASL 2013 替诺福韦（TDF）是安全和耐受性良好，在慢性乙型肝

StephenW

Abstract 744
     
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

StephenW

背景和目的：TDF已经证明持续的HBV抑制和良好的安全性，通过6年，然而，在慢性乙型肝炎患者有轻度肾功能不全（MRI）的数据是有限的，他们被排除大多数试验。 MRI的患者（肌酐清除率50  -  <80毫升/分钟由Cockroft-尔特）TDF与FTC / TDF在拉米夫定耐药的患者（研究121）在一项前瞻性，随机，双盲试验，其中包括没有差异，观察疗效或安全性之间治疗（丰S. AASLD 2012，＃20）。
方法：事后分析研究121相比，MRI检查的患者（74/280，26％）和肾功能正常（NRF，肌酐清除率≥80毫升/分钟）的患者（206/280; 74％）。超过96周的安全，包括骨矿物质密度（BMD）监测DXA，药代动力学（PK; MRI患者只），性和有效性进行了评估。
结果：在基线（BL），平均（SD），肌酐清除率（9）为67毫升/分钟的MRI组和104（18）mL / min的NRF组。两组匹配情况除外：（MRI与NRF）平均年龄58  -  43岁（P <0.001），男性为59％和81％（P <0.001），前IFN 18％和32％（P = 0.015），并事先ADV 14％和25％（P = 0.044）。替诺福韦（TFV）PK参数（AUCτ的Cmax，Tmax分别）在MRI的比较NRF历史数据，TFV风险稳态（AUCτ）和BL肌酐清除率之间无相关性。 TDF的耐受性良好，整体3例（1.1％），停止了研究，早期的AE（2-MRI和1-NRF）。确认没有病人有血清肌酐≥0.5毫克/升，增加1％（2-NRF）瞬态PO4 <2毫克/升。九MRI患者有CLCR <50毫升/分钟（前处理范围：49-61毫升/分钟），稳定与调整剂量。没有差异，观察在超过96周的脊椎或髋骨BMD％的变化，并没有指出在任一组临床相关的骨质流失。 96周时有没有显着性差异（缺少=故障）％，HBV DNA <400拷贝/毫升，ALT复常率，HBeAg阴转/血清学转换。
结论：患者MRI接收TDF的安全性，PK，疗效是相似的到NRF患者;在MRI患者肾骨相关并发症的风险增加，却没有证据。

咬牙硬挺

替诺是好同志啊

9病成医

就是价格高了,穷病人望药兴叹.