Transplant Evidence Alert

The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).

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Association between medication adherence and intrapatient variability in tacrolimus concentration among stable kidney transplant recipients

Sci Rep. 2021 Mar 8;11(1):5397 doi: 10.1038/s41598-021-84868-5.
Abstract

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6-25.5%] and 16.0% [11.5-23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = - 0.067, P = .527; dosing adherence, ρ = - 0.098, P = .352; timing adherence, ρ = - 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: Previous studies have shown an association between intrapatient variability in tacrolimus levels (IPV) and graft outcomes following kidney transplantation. Studies have worked on the assumption that IPV relates to poor adherence, with missed doses and suboptimal dose timing resulting in increased variability. This study investigates the relationship between IPV and adherence in a post-hoc analysis of an RCT using electronic medication monitoring and self-reported adherence. The authors found no relationship between any of the adherence measures used and tacrolimus IPV, suggesting that the use of IPV as a surrogate for compliance is not justified. It should be noted that the population included in this study had a low IPV overall, and previous studies have suggested that the relationship between IPV and adverse outcomes is seen at higher levels than typically seen in patients in the present study. Therefore, selection of a more poorly adherent population at baseline may have led to different findings.
Study Details
Aims: This study is a post-hoc analysis of a randomised controlled trial (RCT) evaluating the effectiveness of a mobile medication manager application in improving medication adherence in renal transplant patients. The aim of this study was to investigate the link between intrapatient variability (IPV) of tacrolimus concentrations and adherence to medication among the renal transplant patients included in the RCT.
Interventions: Participants were randomised to either the mobile group or the control group.
Participants: 92 renal transplant recipients.
Outcomes: The main outcome of interest was the assessment of IPV and the time in therapeutic range (TTR) in the adherent versus the nonadherent group. Additionally, the study measured the incidence of de novo donor-specific antibodies (dnDSA) and estimated glomerular filtration rate (eGFR) between the groups.
Follow Up: 6 months
Metadata
Funding: Funding not described
Publication type: Clinical Trial, Multicenter Study, Randomised Controlled Trial
Trial registration: ClinicalTrials.gov - NCT01905514
Organ: Kidney
Language: English
Author email: surgeonmsi@gmail.com
MeSH terms: Adolescent; Adult; Aged; Female; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Medication Adherence; Middle Aged; Prospective Studies; Self Report; Tacrolimus; Transplant Recipients; WM0HAQ4WNM (Tacrolimus)