Improved Survival in Liver Transplant Recipients Receiving Prolonged-Release Tacrolimus in the European Liver Transplant Registry

Abstract

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long‐term outcomes with prolonged‐release tacrolimus versus tacrolimus BD in liver transplantation (January 2008–December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score‐matching for baseline demographics. Patients with <1 month of follow‐up were excluded from the analyses. In total, 4367 patients (prolonged‐release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score‐matched patients confirmed the significant survival advantages observed in the prolonged‐release tacrolimus‐ versus tacrolimus BD‐treated group. This large retrospective analysis from the ELTR identified significant improvements in long‐term graft and patient survival in patients treated with prolonged‐release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Advancing Transplantation

“…Data from the ELTR have provided valuable insights in liver transplantation, including information regarding the use of organs from marginal donors, 15 and the development of a risk-analysis model to determine mortality risk of a given procedure in an individual patient. 17 Adam et al 18 recently reported an analysis of data from the ELTR comparing long-term graft and patient survival data for all adult patients transplanted between January 2008 and December 2012 who received tacrolimus-based immunotherapy. The patient groups were stratified by the tacrolimus formulation they received during the first month posttransplant (prolonged-release vs immediate-release formulation).…”

“…To prevent center bias, only data from the 21 centers who had been using both tacrolimus formulations were included. 18 Data for 4367 patients were analyzed (528 patients receiving prolonged-release tacrolimus and 3839 patients receiving immediate-release tacrolimus). 18 In this study, the group of patients receiving prolonged-release tacrolimus demonstrated a significantly higher rate of graft survival compared with the group receiving immediate-release tacrolimus over 3 years of treatment (88% vs 80%, respectively; P = 0.01).…”

“…18 Data for 4367 patients were analyzed (528 patients receiving prolonged-release tacrolimus and 3839 patients receiving immediate-release tacrolimus). 18 In this study, the group of patients receiving prolonged-release tacrolimus demonstrated a significantly higher rate of graft survival compared with the group receiving immediate-release tacrolimus over 3 years of treatment (88% vs 80%, respectively; P = 0.01). The numeric difference of 8% between the treatment arms amounts to a 10% improvement in long-term graft function, or, in other terms, a 40% risk reduction of graft loss.…”

“…In the multivariate analysis, the 3 highest-ranking risk factors for reduced graft and patient survival were found to be HIV-positive serology (risk ratio: 3.40, 3.41, respectively), serum creatinine concentration of ≥2 mg/dL (risk ratio: 1.84, 1.86, respectively), and treatment with immediate-release tacrolimus immunotherapy versus prolonged-release tacrolimus (risk ratio: 1.81, 1.72, respectively) ( Table 1). Adam et al 18 went on to report 3-year Kaplan-Meier data showing an 8% graft survival advantage in the group receiving prolonged-release tacrolimus versus those in the immediate-release tacrolimus group (P = 0.01) ( Figure 2) and a 6% (nonstatistically significant) trend toward improved patient survival in the group receiving prolonged-release tacrolimus versus those in the immediate-release tacrolimus group (P = 0.07). Longerterm follow-up data for patients in the ELTR and an analysis of patients who switched between formulations after month 1 are ongoing.…”

“…Adam et al 18 carried out further analyses on a refined population to account for discrepancies in the baseline characteristics between the 2 treatment groups using propensity score matching (where patients were paired according to similar predefined baseline characteristics, which had been identified as significant risk factors in previously carried out univariate and multivariate risk analyses) on a 1:2 ratio (prolonged-release tacrolimus:immediate-release tacrolimus). When the authors analyzed data from these 810 patients (270 prolonged-release, 540 immediate-release tacrolimus) they confirmed a significant graft survival advantage associated with the use of prolongedrelease versus immediate-release tacrolimus over 3 years in both the univariate and Kaplan-Meier analyses.…”