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

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.

Figure 1

Differences in IPV indices between adherent and nonadherent groups measured through an electronic monitoring system (a) and self-report (b). CV, coefficient variation; IPV, intrapatient variability; IQR, interquartile range; MAD, mean absolute deviation.

Figure 2

Correlation between intrapatient variability indices and adherence measured by the medication event monitoring system.

Figure 3

Correlation analysis using Spearman’s rho to identify correlations between adherence measures using the medication event monitoring system and intrapatient variability indices. Taking adherence (a), dosing adherence (b), timing adherence (c). CV, coefficient variation; MAD, mean absolute deviation.

Figure 4

The development of dnDSA in terms of taking adherence (a) and IPV (b). IPV, intrapatient variability; CV, coefficient variation; dnDSA, de novo donor-specific antibodies; IQR, interquartile range.