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Observational Study
. 2022 Mar;36(3):e14550.
doi: 10.1111/ctr.14550. Epub 2021 Dec 17.

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study

Constantino Fernandez Rivera  1 , María Calvo Rodríguez  1 , José Luís Poveda  2 , Julio Pascual  3 , Marta Crespo  3 , Gonzalo Gomez  4 , Sheila Cabello Pelegrin  4 , Javier Paul  5 , Ricardo Lauzurica  6 , Mònica Perez Mir  6 , Francesc Moreso  7 , Manel Perelló  7 , Amado Andres  8 , Esther González  8 , Ana Fernandez  9 , Alicia Mendiluce  10 , Beatriz Fernández Carbajo  10 , Ana Sanchez Fructuoso  11 , Natividad Calvo  11 , Alejandro Suarez  12 , Gabriel Bernal Blanco  12 , Antonio Osuna  13 , M Carmen Ruiz-Fuentes  13 , Edoardo Melilli  14 , Nuria Montero Perez  14 , Ana Ramos  15 , Beatriz Fernández  15 , Verónica López  16 , Domingo Hernandez  16 ; Better study
Affiliations
Observational Study

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study

Constantino Fernandez Rivera et al. Clin Transplant. 2022 Mar.

Abstract

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P < .001) with similar Cmin and 30% lower TDD levels (P < .0001). The incidence of treatment failure was 3.9% in the LCPT group and 9.0% in the PR-Tac group (P = .117). Study discontinuation rates were 6.2% in the LCPT group and 12.4% in the PR-Tac group (P = .113). Adverse events, renal function and other complications were comparable between groups. The median accumulated dose of tacrolimus in the LCPT group from day 14 to month 6 was 889 mg. Compared to PR-Tac, LCPT showed higher relative bioavailability, similar effectiveness at preventing allograft rejection, comparable effect on renal function, safety, adherence, treatment failure and premature discontinuation rates.

Keywords: bioavailability; clinical practice; pharmacokinetics; renal transplantation; tacrolimus; treatment failure.

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Conflict of interest statement

Constantino Fernández has received honoraria from Alexion, Novartis, Astelas, Chiesi, and Biotest. Amado Andres has received honoraria from Chiesi, Astellas, Novartis and Bristol‐Myers‐Squibb. Domingo Hernandez and Veronica López received honoraria from Chiesi. Francesc Moreso received honoraria from Chiesi, Astellas, Novartis and Bristol‐Myers‐Squibb. Edoardo Melilli received honoraria from Chiesi, Astellas, Novartis, Sandoz, Menarini. Gonzalo Gómez has received lecture fees from speaking on behalf of Novartis, and has been paid advisory boards by Alexion. Ana Sánchez Fructuoso has received honoraria from Chiesi. The rest of the authors report no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart showing the study design. Tac, tacrolimus
FIGURE 2
FIGURE 2
Trough levels and total daily doses over the study period in the LCPT and PR‐Tac groups. Graphs show mean ± SD levels for: A, Trough levels (Cmin), B, TDD (total daily dose). * P‐value < .05
FIGURE 3
FIGURE 3
Relative bioavailability of tacrolimus over the study period in the LCPT and PR‐Tac groups. The graph shows mean ± SD for normalized blood tacrolimus levels (Cmin/TDD) over 6 months of follow‐up. * P‐value < .0001
FIGURE 4
FIGURE 4
Evolution of quality of life in tremor. Bar graphs show QUEST scores at A, Visit 1 and B, Visit 5. * P‐value < .05
FIGURE 5
FIGURE 5
Evolution of renal function measured by creatinine clearance (CrCl) over the study period. No significant differences between groups were observed. The change in CrCl was statistically significant from Visit 2 to 4 in the LCPT group and from Visit 2 to 3 in the PR‐Tac group
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