Safety and Effectiveness of Once-Daily, Prolonged-Release Tacrolimus in De Novo Kidney Transplant Recipients: 5-year, Multicenter Postmarketing Surveillance in Japan.

ABSTRACT

This study reported 5-year data on the safety and effectiveness of prolonged-release tacrolimus (PR-T) in de novo kidney transplant recipients (KTRs) in Japanese routine clinical practice. METHODS: This was an open-label, prospective, noncomparative, observational, postmarketing surveillance study of de novo KTRs who initiated PR-T as part of routine clinical practice in 43 sites in Japan between March 2009 and March 2011. Follow-up period was March 2010 to March 2016. Effectiveness outcomes included Kaplan-Meier estimated patient survival, graft survival, graft rejection, estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease-4), and creatinine clearance. Adverse drug reactions (ADRs) were recorded. RESULTS: The safety analysis set comprised 250 de novo KTRs (mean age 45.9 [SD, 14.2] years); 249 patients formed the efficacy analysis set. Mean PR-T daily dose decreased during the study (0.14 [SD, 0.05], 0.09 [SD, 0.05], and 0.05 [SD, 0.03] mg/kg at day 0 [transplant], week 24, and year 5, respectively), as did tacrolimus trough levels (15.9 [SD, 13.4] to 4.0 [SD, 1.4] ng/mL between day 1 and year 5). Year 5 Kaplan-Meier estimated patient survival, graft survival, and rejection rates were 96.7%, 93.4%, and 26.9%, respectively. Mean eGFR and serum creatinine levels remained stable from week 4 to year 5 post transplant (eGFR, 48.3 [SD, 16.9] vs 48.7 [SD, 13.8] mL/min/1.73 m2, respectively; serum creatinine, 1.39 [SD, 0.89] vs 1.25 [SD, 0.50] mg/dL). Overall, 230 ADRs were reported in 129 (51.6%) patients. Eight patients died during follow-up. CONCLUSION: PR-T-based immunosuppression was effective, and renal function remained stable up to 5 years post transplant in routine clinical practice in Japan. Incidence of ADRs was low, and no new safety signals were identified.