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.

Rubik, Jacek;Debray, Dominique;Kelly, Deirdre;Iserin, Franck;Undre, Nasrullah;et.al.
(2019) Transplant international — Vol. 32, n° 11, p. 1182-1193 (2019)

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Authors
  • Rubik, Jacek
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  • Debray, Dominiqueorcid-logo
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  • Kelly, Deirdre
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  • Iserin, Franck
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  • Reding, RaymondUCLouvain
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  • Undre, Nasrullahorcid-logo
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Abstract
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.
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Rubik, J., Debray, D., Kelly, D., Iserin, F., Webb, N. J. A., Czubkowski, P., Vondrak, K., Sellier-Leclerc, A.-L., Rivet, C., Riva, S., Tönshoff, B., D’Antiga, L., Marks, S. D., Reding, R., Kazeem, G., & Undre, N. (2019). 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. Transplant international, 32(11), 1182-1193. https://doi.org/10.1111/tri.13479 (Original work published 2019)