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TRough versus AUC Monitoring of cyclosporine: A randomized comparison of adverse drug reactions in adult allogeneic stem cell recipients (TRAM study)
Author(s) -
Kuijvenhoven Marianne A.,
Wilhelm Abraham J.,
Meijer Ellen,
Janssen Jeroen J. W. M.,
Swart Eleonora L.
Publication year - 2021
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13674
Subject(s) - medicine , therapeutic drug monitoring , dosing , toxicity , adverse effect , trough concentration , area under the curve , trough level , gastroenterology , transplantation , clinical endpoint , pharmacokinetics , incidence (geometry) , randomized controlled trial , pharmacology , tacrolimus , physics , optics
Objective To investigate the incidence and severity of adverse drug reactions of cyclosporine using AUC‐targeted therapeutic drug monitoring (TDM) compared to trough level (C trough )‐targeted TDM in adult allogeneic stem cell recipients. Methods Blind, monocenter, intervention study. Subjects were 1:1 randomized into either an AUC group or a C trough group. Adverse drug reactions were accessed two and four weeks after start of treatment. Results Forty patients were included, resulting in 15 evaluable subjects (AUC group) and 13 evaluable subjects (C trough group). Grade two/three toxicity was observed in 46% (C trough group) versus 60% of subjects (AUC group) ( P = .463). There was no significant difference between two and four weeks after start of cyclosporine for nausea ( P = .142 resp. P = .122), renal dysfunction ( P = .464 resp. P = 1.000), and hypomagnesemia ( P = 1.000 resp. P = .411). Subjects in the AUC group reached the therapeutic goal earlier (72,7% versus 43,0% at third sampling point, P = .332) and were within the target range more consistently. Conclusion This study showed no reduction in incidence and severity of cyclosporine‐induced toxicity with AUC‐ versus trough level‐targeted TDM. Although modeled dosing based on AUC led to faster optimal target attainment, this did not result in less toxicity in the early days after transplantation.