22. No clear influence of non-adherence on tacrolimus intra-patient variability in stable kidney transplant recipients’

S.R.M. Gokoel, T.C. Zwart, D.J.A.R. Moes, P.J.M. van der Boog, J.W. de Fijter

Thursday 5 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 5 – Klinische en Verpleegkundige abstracts

Background: High intra-patient variability (IPV) in tacrolimus exposure has been associated with a higher risk of graft rejection and graft loss. Several factors may increase IPV of tacrolimus exposure. Recent literature states that medication non-adherence (MNA) has highest impact on IPV and is also the most modifiable risk factor. However, while the association between high IPV in tacrolimus exposure and reduced long-term graft results is established, the relation between tacrolimus IPV and MNA is not clearly established yet.

The objective of this study is to assess the correlation between tacrolimus IPV and MNA.

Methods: 64 Kidney(pancreas) transplant recipients from an ongoing single centre trial were enrolled in this study. MNA was assessed through daily electronic monitoring (EM) of tacrolimus intake, patient-reported questionnaire (Immunosuppressant Therapy Adherence Scale), physician rating by one nephrologist, tacrolimus time-in-therapeutic range (TTR venous trough concentrations (C₀); TTR dried blood spot (DBS) area-under-the-concentration-time-curve (AUC)) and a previously developed composite adherence score. Tacrolimus C₀-concentrations were collected from 5 sampling instances and DBS AUCs were collected from 3 sampling instances. IPV of dose-corrected C₀ and AUC was expressed with the coefficient of variation (CV= ((standard deviation/mean)*100). The correlation between tacrolimus IPV as a continuous variable and the separate MNA markers was assessed. Also, the separate MNA markers were compared in stratified tacrolimus IPV groups (cut-off 20%) based on previous literature.

Results: MNA rates were 7%, 31.1%, 28.1%, 40.6%, 61.7%, 68.9%, according to EM, self-report, physician rating, TTR C₀, TTR AUC and CAS, respectively. Mean tacrolimus IPV was 17.9% (Sd ±11.1%) and 20.2% (±12.6%), respectively for C₀-concentrations and AUCs. No correlation between continuous tacrolimus IPV and MNA was found (highest Pearson R² = 0.22 for tacrolimus AUC IPV versus TTR AUC). Patients with IPV <20% were significantly more adherent according to self-report (p=0.035) and TTR AUC (p=0.030).

Conclusions: A large variation in MNA prevalence was found after assessment with various diagnostic markers. No significant correlation between tacrolimus IPV and MNA was found. Only after stratification of tacrolimus IPV with a 20% cut-off, a significant difference in adherence was found with self-report and TTR AUC.