Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus: A Multicenter, Randomized Controlled Trial.

Autor:	Mulder MB; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands., van Hoek B; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Polak WG; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Alwayn IPJ; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands., de Winter BCM; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands., Darwish Murad S; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Verhey-Hart E; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Elshove L; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Erler NS; Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Hesselink DA; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., den Hoed CM; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Metselaar HJ; Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Transplantation direct [Transplant Direct] 2024 Mar 12; Vol. 10 (4), pp. e1612. Date of Electronic Publication: 2024 Mar 12 (Print Publication: 2024).
DOI:	10.1097/TXD.0000000000001612
Abstrakt:	Background: The aim of this open-label, multicenter, randomized controlled study was to investigate whether the life cycle pharma (LCP)-tacrolimus compared with the extended-release (ER)-tacrolimus formulation results in a difference in the prevalence of posttransplant diabetes, hypertension and chronic kidney disease (CKD) at 12 mo after liver transplantation. Methods: Patients were 1:1 randomized to either of the 2 tacrolimus formulations. The primary endpoint was defined as a composite endpoint of any of 3 events: sustained (>3 mo postrandomization) posttransplant diabetes, new-onset hypertension, and/or CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m ² for >3 m during the follow-up. Results: In total, 105 patients were included. In the intention-to-treat analysis, a statistically significant lower proportion of liver transplant recipients in the LCP-tacrolimus group reached the composite primary endpoint at 12 mo compared with the ER-tacrolimus group (50.9% [27/53], 95% confidence interval [CI], 37.9%-63.9% versus 71.2% [37/52], 95% CI, 57.7%-81.7%; risk difference: 0.202; 95% CI, 0.002-0.382; P = 0.046). No significant difference was found in the per protocol analysis. In the intention-to-treat and per protocol population, fewer liver transplant recipients in the LCP-tacrolimus group developed CKD and new-onset hypertension compared with the ER-tacrolimus group. No differences in rejection rate, graft and patient survival were found. Conclusions: A statistically significant and clinically relevant reduction in the prevalence of the composite primary endpoint was found in the LCP-tacrolimus group compared with the ER-tacrolimus group in the first year after liver transplantation with comparable efficacy. Competing Interests: D.A.H. has received lecture fees and consulting fees from Astellas Pharma, Astra Zeneca, Chiesi Pharma, Medincell, Novartis Pharma, Sangamo Therapeutics, and Vifor Pharma. He has received grant support from Astellas Pharma, Bristol-Myers Squibb, and Chiesi Pharma (paid to his institution). D.A.H. does not have employment or stock ownership at any of these companies, and neither does he have patents or patent applications. H.J.M. has received lecture fees from Astellas Pharma and received grant support from Astellas Pharma, Novartis Pharma, and Chiesi Pharma. C.M.d.H. has received lecture fees and consulting fees from Chiesi Pharma, Takeda, Novartis Pharma, and Abacus medical and travel grants from Orphalan. C.M.d.H. does not have employment or stock ownership at any of these companies, and neither does he have patents or patent applications. The other authors declare no conflicts of interest. (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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