Five-Year Real-World Clinical Outcomes in Kidney Transplant Recipients Switching to Prolonged-Release Tacrolimus

Abstract

Background: Tacrolimus trough-level concentration variability and patient non-adherence are risk factors for poorer graft and patient survival. This study investigated long-term outcomes in kidney transplant recipients who were converted from twice-daily immediate-release tacrolimus to once-daily prolonged-release tacrolimus. Material/Methods: CHORUS (NCT02555787) is a 5-year, real-world, prospective, global, non-interventional study. Kidney transplant recipients (KTRs; >= 18 years, N=4389) were grouped by post-transplant conversion timing (early converters [ECs], <= 6 months; late converters [LCs], >6 months). The primary endpoint was the change from baseline in estimated glomerular filtration rate (eGFR) from conversion to 5 years. Secondary endpoints included tacrolimus dose and trough levels, clinical and biopsy-proven acute rejection (BPAR), graft and patient survival, emergence of donor-specific antibodies, and safety. Results: The full analysis set included 4028 patients (1060 ECs and 2968 LCs). Overall, eGFR remained stable 5 years after conversion, with a mean change from baseline of-1.4 (early converters, 3.4; late converters,-3.0) mL/min/1.73 m2. Mean daily tacrolimus dose and trough levels remained stable 5 years after conversion. Clinically-diagnosed and BPAR-free survival 5-year estimates were 91.2% and 93.9%, respectively. Graft and patient 5-year survival estimates were 95.0% and 97.1%, respectively. Donor-specific antibodies (DSA) occurrence was observed in 4.9% of patients after conversion. Prolonged-release tacrolimus (PRT)-related adverse events were reported by 19.3% of patients and were the cause of discontinuation in 5.5% of patients. Conclusions: In this large and diverse cohort of KTRs, conversion to PRT, independent of conversion timing, was effective and well tolerated in routine clinical practice, supporting its continued long-term use.