Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis

Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis

A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrati...

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Bibliographic Details
Published in:Annals of hematology Vol. 96; no. 6; pp. 935 - 942
Main Authors: Moiseev, Ivan Sergeevich, Burmina, Ekaterina Andreevna, Muslimov, Albert Radikovich, Pirogova, Olga Vladislavovna, Bondarenko, Sergey Nikolaevich, Darskaya, Elena Igorevna, Tarakanova, Yuliya Alexandrovna, Senina, Nadegda Georgievna, Afanasyev, Boris Vladimirovich
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2017
Springer Nature B.V
Subjects:
Adolescent
Adult
Aged
Cyclosporine - pharmacokinetics
Cyclosporine - therapeutic use
Female
Graft vs Host Disease - etiology
Graft vs Host Disease - metabolism
Graft vs Host Disease - prevention & control
Hematologic Neoplasms - therapy
Hematology
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cell Transplantation - methods
Humans
Immunosuppressive Agents - pharmacokinetics
Immunosuppressive Agents - therapeutic use
Male
Medicine
Medicine & Public Health
Middle Aged
Multivariate Analysis
Oncology
Original Article
Risk Factors
Survival Analysis
Tacrolimus - pharmacokinetics
Tacrolimus - therapeutic use
Transplantation, Homologous
Young Adult
Graft-versus-host disease
Cyclosporine A
Tacrolimus
Allogeneic stem cell transplantation
Pharmacokinetics
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Summary:A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrations, variability of concentrations, and failures to maintain target levels that distinguished patients with low, intermediate, and high risks of acute GVHD (hazard ratios (HR) 1.77, 95%CI 1.36–2.32, p  < 0.0001). This model was used to compare 95 patients with CsA and 239 with Tac GVHD prophylaxis. In the multivariate analysis, incorporating PK risk, no differences were observed for grade II–IV acute GVHD (HR 0.73, 95%CI 0.48–1.10, p  = 0.13), but grade III–IV acute GVHD was lower in the Tac group (HR 0.47, 95%CI 0.28–0.78, p  = 0.004). The observed difference was due to patients with high PK risk (HR 0.377, 95%CI 0.19–0.75, p  = 0.005), but not with low and intermediate PK risk ( p  > 0.05). Patients in the Tac group had better GVHD relapse-free survival (HR = 0.659, p  = 0.01) and comparable overall survival ( p  > 0.05). In conclusion, PK risk should be accounted for in comparisons of GVHD prophylaxis regimens with calcineurin inhibitors, and Tac was superior to CsA in patients with high, but not intermediate and low PK risk.
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-017-2975-0