ABSTRACT
BACKGROUND: Reliable methods to detect and reduce medication nonadherence in solid organ-transplanted (SOT) adolescents are warranted. We aimed to evaluate the feasibility of combining a medication-manager application (TusenTac®-app) with home-sampling of tacrolimus (Tac) in young SOT recipients. METHODS: Kidney and combined SOT recipients between 14 and 25 years were included. During an 8-week intervention period, the participants were instructed to use the transplant-specific, age-adapted TusenTac®-app daily and to perform weekly at-home Tac trough finger-prick microsampling. Microsample Tac concentrations were controlled against timed venous samples twice. Medication implementation and persistence adherence were measured with BAASIS© questionnaires, TusenTac®-registrations, Tac trough concentration coefficient of variation (CV%) and self-reporting by interview. For comparison, venous Tac trough CV% were obtained from the year before and after the short-term intervention. RESULTS: Twenty-two recipients were included, two withdrawals, leaving 20; median age 17.9 (14.5-24.8) years, 12 females (60%). The participants registered their dosage intake 88% (1502/1703) of the expected times, and 90% (106/118) of the microsamples were obtained correctly. At inclusion, 11 recipients (55%) were nonadherent assessed with BAASIS© questionnaire, four of these (36%) turned adherent during the intervention period. At the end, 70% reported improved timing-adherence at the interview. There was no significant change in TacCV% from the year before to the year after the short-term intervention. Home-sampling was reliable and measured Tac concentrations accurately. CONCLUSIONS: Home-monitoring, combining Tac finger-prick microsampling and a medication-manager app, is feasible in adolescent SOT recipients with 70% perceived improvement in medication timing-adherence. There were no significant long-term changes in TacCV% confirming the need for continuous use and individualized interventions.
ABSTRACT
BACKGROUND: Therapeutic drug monitoring of tacrolimus (Tac) is mandatory in solid organ transplant (SOT) recipients. Finger-prick microsampling is more flexible and tolerable during the therapeutic drug monitoring of tacrolimus and has been shown to be applicable in adult SOT recipients. In this study, a previously validated method applying volumetric absorptive microsampling (VAMS) to measure Tac in adults was cross-validated in a pediatric population. METHODS: Patients with SOT scheduled for standard posttransplant follow-up visits were recruited. Blood samples were obtained by trained phlebotomists using standard venipuncture and capillary microsampling, before the morning dose of Tac as well as 2 and 5 hours after dosing. Tac concentrations were quantified using liquid chromatography-tandem mass spectrometry. Concordance between Tac concentrations obtained with venipuncture and VAMS was evaluated using Passing-Bablok regression, calculation of absolute and relative differences, and percentage of samples within ±20% and ±30% difference. RESULTS: A total of 39 SOT patients aged 4-18 years (22 male) were included. The median (range) predose venous blood concentration was 4.8 (2.6-13.6) mcg/L, with a difference between VAMS and venous blood samples of -0.2 ± 0.7 mcg/L. The relative mean difference was -1.3% [95% confidence interval (CI), -5.9% to 3.4%]. Ninety-two percent and 97% of the sample pairs demonstrated differences within ±20% and ±30%, respectively. Postdose (2 hours and/or 5 hours, n = 17) median concentration in venous blood was 7.9 (4.8-19.2) mcg/L. The difference between VAMS and venous blood samples was 0.1 ± 1.0 mcg/L, with a relative mean difference of -2.5% (95% confidence interval, -8.8% to 3.8%). Eighty-eight percent of the postdose sample pairs were within ±20% difference, and all were within ±30% difference. CONCLUSIONS: Tac concentrations can be accurately measured using VAMS technology in pediatric SOT recipients. This makes home-based Tac monitoring feasible in the pediatric population.
