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CHRONIC HBV PATIENTS WHO SWITCHED TO TENOFOVIR ALAFENAMIDE (TAF) AFTER EITHER 2 OR 3 YEARS OF PRIOR TENOFOVIR DISOPROXIL FUMARATE (TDF) TREATMENT DEMONSTRATED IMPROVEMENT IN BONE AND RENAL SAFETY
Maria Buti, Namiki Izumi, Young-Suk Lim, Harry L. Janssen, Jia-Horng Kao, AdrianStreinu-Cercel, Elena Nurmukhametova, Xiaoli Ma, Omer Tabak, Maciej Jablkowski,Vithika Suri, John F. Flaherty, Audrey H. Lau, Anuj Gaggar, Shuyuan Mo, Abhijit Choudhury, Scott Fung, Wan-Long Chuang, Edward GaneBackground and Aims:TAF, a novel prodrug of tenofovir, has shown similar efficacy toTDF in Phase 3 studies with less bone and renal effects. As part of a protocol amendment to extend double blind (DB) treatment for 1 additional year (Week 96 to Week 144), only~50% consented in time for this change; the remainder had already been receiving open-label (OL) TAF after Week 96. Here, we evaluate the 4 year (Week 192) safety and efficacy of switching to OL TAF in patients who had received DB TDF treatment for either 2 or 3years.Method:In 2 identically-designed studies, 1298 HBeAg-negative and HBeAg-positive CHB patients (873 TAF, 425 TDF) were randomized and treated with either TAF or TDF.In the TDF group, 180 patients were switched to OL TAF at Week 96 (OL TAF 96 Wk),while 202 patients switched from DB TDF to OL TAF at Week 144 (OL TAF 48 Wk). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG]) parameters, viral suppression, and biochemical responses were assessed at week 192 using the time of rollover to TAF as the respective OL baseline (BL). Withingroup changes in bone and renal parameters were assessed by paired t test or Wilcoxonsigned rank test. Results: Patient characteristics were similar for those receiving OL TAF for 1 or 2 years following DB TDF treatment. Significant increases in eGFRCGfrom OL BL were observed within each group at Week 192 (Table). Significant increases in hip and spine BMD from OL BL occurred within each group, the magnitude was greater after 2 years of OL TAF only for hip BMD. Within each group, virologic suppression (HBV DNA<29IU/mL) was maintained from OL BL to Week 192 in patients who remained on TAF treatment(OL TAF 96 Wk group: 88% and 88%; OL TAF 48 Wk group: 94% and 93%, respectively),while at Week 192, within each group the rate of ALT normalization by 2018 AASLD criteria increased from OL BL after switching to TAF (55% OL TAF 96 Wk and 37% OL TAF 48Wk).Conclusion:In CHB patients treated with TDF for 2 or 3 years, recovery of renal and bone parameters occurred at Year 4 suggesting reversibility of these parameters. Virologiccontrol was maintained and ALT normalization increased following the switch from TDF to TAF. |
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发表于 2019-5-20 16:43
