Efficacy of prolonged- and immediate-release tacrolimus in kidney transplantation

• Verfasst von: Krämer, Bernhard [VerfasserIn]
• Titel: Efficacy of prolonged- and immediate-release tacrolimus in kidney transplantation
• Titelzusatz: a pooled analysis of two large, randomized, controlled trials
• Verf.angabe: B.K. Krämer, L. Albano, B. Banas, B. Charpentier, L. Bäckman, H. Tedesco-Silva, F. Lehner, G.A. Mondragón-Ramírez, M. Glyda, E. Cassuto-Viguier, O. Viklický, G. Mourad, P. Rigotti, S. Schleibner, and N. Kamar
• E-Jahr: 2017
• Jahr: November 2017
• Umfang: 10 S.
• Fussnoten: Gesehen am 08.11.2018
• Titel Quelle: Enthalten in: Transplantation proceedings
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1997
• Jahr Quelle: 2017
• Band/Heft Quelle: 49(2017), 9, Seite 2040-2049
• ISSN Quelle: 1873-2623
• DOI: doi:10.1016/j.transproceed.2017.07.011
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1582691908

Abstract

Background: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). Methods. Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). Results Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). Conclusions Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged-release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation. ClinicalTrials.govNCT00189839; NCT00717470.