A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study

Background: In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. Material/Methods: A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. Results: Baseline clinical and demographic characteristics were similar between the two cohorts. The mean +/- SD ratio of conversion of tacrolimus dose was 1.04+0.28; 1.01 +/- 0.28 (early) and 1.08 +/- 0.28 (late) (p=0.0247). The mean +/- SD time from conversion to the first tacrolimus trough blood concentration was 30.8 +/- 42.8 days; 24.8 +/- 45.4 days (early) and 37.5 +/- 38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician's preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. Conclusions: Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.