1.
Efficacy and safety of tacrolimus compared with ciclosporin-A in renal transplantation: 7-year observational results.
Krämer, BK, Montagnino, G, Krüger, B, Margreiter, R, Olbricht, CJ, Marcen, R, Sester, U, Kunzendorf, U, Dietl, KH, Rigotti, P, et al
Transplant international : official journal of the European Society for Organ Transplantation. 2016;(3):307-14
Abstract
The European Tacrolimus versus Ciclosporin-A Microemulsion (CsA-ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months. Primary endpoints of this investigator-initiated, observational 7-year follow-up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, and patient death). We analyzed data from the original intent-to-treat population (n = 557; 286 tacrolimus, 271 CsA-ME). A total of 237 tacrolimus and 208 CsA-ME patients provided data. At 7 years, Kaplan-Meier estimated rates of patients free from BPAR were 77.1% in the tacrolimus arm and 59.9% in the CsA-ME arm, graft survival rates amounted to 82.6% and 80.6%, and patient survival rates to 89.9% and 88.1%. Estimated combined endpoint-free survival rates were 60.2% in the tacrolimus arm and 47.0% in the CsA-ME arm (P = <0.0001). A higher number of patients from the CsA-ME arm crossed over to tacrolimus during 7 year follow-up: 19.7% vs. 7.9% (P = <0.002). More patients in the tacrolimus group stopped steroids and received immunosuppressive monotherapy. Significantly, more CsA-ME patients received lipid-lowering medication and experienced cosmetic and cardiovascular adverse events. Tacrolimus-treated renal transplant recipients had significantly higher combined endpoint-free survival rates mainly driven by lower acute rejection rates despite less immunosuppressive medication at 7 years.
2.
Effect of cyclosporine on steady-state pharmacokinetics of MPA in renal transplant recipients is not affected by the MPA formulation: analysis based on therapeutic drug monitoring data.
Trkulja, V, Lalić, Z, Nađ-Škegro, S, Lebo, A, Granić, P, Lovrić, M, Pasini, J, Božina, N
Therapeutic drug monitoring. 2014;(4):456-64
Abstract
BACKGROUND Two oral mycophenolic acid (MPA) formulations, immediate-release mycophenolate mofetil and enteric-coated mycophenolate sodium, have been shown to differ regarding some drug-drug interactions. The aim was to assess whether the effects of cyclosporine (CsA) on steady-state pharmacokinetics (PK) of MPA in renal transplant patients were affected by MPA formulation. METHODS A prospective, stratified observational study based on therapeutic drug monitoring of MPA (6 total plasma concentrations over a 12-hour dosing interval, τ) in consecutive stable adult renal transplant recipients (n = 68). RESULTS Patients treated with enteric-coated mycophenolate sodium (n = 45) or mycophenolate mofetil (n = 23) and with either CsA (microemulsion, n = 43) or tacrolimus (Tac) (immediate release, n = 25) were comparable regarding demographics, comorbidity, renal and liver functions, comedication, corticosteroid dose, CsA or Tac dose, and trough concentrations. Based on dose-normalized MPA concentrations and with adjustment for age, sex, body mass index, estimated glomerular filtration rate, and corticosteroid dose, CsA (as compared with Tac) consistently reduced MPA area under the concentration-time curve during the dosing interval at steady state overall [geometric mean ratio (GMR), 0.78; 95% confidence interval, 0.62-0.99] and by MPA formulation (by 22% and 21%, respectively), increased CLT/F,ss overall (1.31; 1.00-1.70) and by formulation (by 25% and 36%, respectively), reduced morning predose MPA concentration overall (0.59; 0.38-0.92) and by formulation (by 34% and 47%, respectively), increased peak-trough fluctuation overall (1.51; 1.06-2.17) and by formulation (by 58% and 45%, respectively), and prolonged tmax,ss overall (adjusted median difference 0.58, 0.04-1.12 hours) and by formulation (by 0.6 and 0.5 hours, respectively). CONCLUSIONS Qualitatively and quantitatively, the effect of CsA on steady-state PK of MPA is not conditional on MPA formulation.