Efficacy and safety of prolonged‐release tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus – a Phase 2, open‐label, single‐arm, one‐way crossover study

摘要

Summary There are limited clinical data regarding prolonged‐release tacrolimus ( PR ‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR ‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16?years) over 1?year following conversion from immediate‐release tacrolimus ( IR ‐T), on a 1:1?mg total‐daily‐dose basis. Endpoints included the incidence of acute rejection ( AR ), a composite endpoint of efficacy failure (death, graft loss, biopsy‐confirmed AR , and unknown outcome), and safety. Tacrolimus dose and whole‐blood trough levels (target 3.5–15?ng/ ml ) were also evaluated. Overall, 79 patients (kidney, n ?=?48; liver, n ?=?29; heart, n ?=?2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow‐up visits had trough levels below the target range. Two (2.5%) patients had AR , and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug‐related treatment‐emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR ‐T to PR ‐T conversion is effective and well tolerated over 1?year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.