Exploratory Analysis of the Impact of an mHealth Medication Adherence Intervention on Tacrolimus Trough Concentration Variability: Post Hoc Results of a Randomized Controlled Trial

Abstract

Background: Medication nonadherence is a leading cause of late allograft loss in kidney transplantation (KT). Tacrolimus trough coefficient of variation (CV), measured using the coefficient of variation, is strongly correlated with acute rejection, graft function, and graft loss. Objective: The objective of this study was to determine if this mobile health (mHealth) intervention aimed at improving medication adherence in a nonadherent KT population would affect high intrapatient tacrolimus variability. Methods: A 6-month, prospective, parallel-arm, randomized controlled clinical trial was conducted to determine the effects of an mHealth intervention on tacrolimus CV. Intervention arm participants utilized an electronic medication tray and an mHealth app to monitor home-based adherence. Tailored motivational reinforcement messages were delivered to promote competence for adherence. Tacrolimus CV was measured using a 12-month rolling average, assessed at monthly intervals (6-month intervention period and 6 months after completion of the study); 80 were included, 40 in each arm. Results: At baseline, tacrolimus CV was similar between arms (37% ± 15% intervention, 37% ± 13% control, P = 0.894). Patients randomized to the intervention had a significant reduction in mean 12-month tacrolimus CVs ( P = 0.046) and a significant improvement in the proportion achieving low tacrolimus CV (tacrolimus CV < 40%; P = 0.001), as compared with the control arm. Conclusion and Relevance: High tacrolimus CV is a risk factor for acute rejection and graft loss; these results offer the potential promise of improved medication adherence and clinical outcomes through the use of innovative technology.

Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective

“…Tacrolimus CV after intervention was significantly lower in the intervention group compared with the control group (p = 0.046). There was also a significant reduction in tacrolimus CV in patients with CV less than 40% (p = 0.001) in conjunction with an improvement in medication adherence as determined by electronic pillbox use (p < 0.001) 73 . Mobile health techniques to reduce IPV through improved adherence have had mixed results, but application of such interventions may benefit tech savvy patients or patients with low baseline adherence but confirmation from additional studies is necessary.…”

“…Retrospective studies utilizing physician records, patient report, or clinic nonattendance to define MNA have not consistently supported a relationship between MNA and IPV 15,28,50,53 . Conflicting results have also been observed among prospective studies assessing MNA using electronic monitoring or rigorous multimodal approaches 65,73,80–82 . Although some discordance may be related to data quality pertaining to the method(s) of defining MNA or small patient population, clinicians must evaluate IPV in a patient‐specific context, including all other possible sources of IPV.…”

Adoption of a novel smart mobile‐health application technology to track chronic immunosuppression adherence in solid organ transplantation: Results of a prospective, observational, multicentre, pilot study

“…Self‐reporting methods through specific questionnaires may be useful to detect poor adherent patients, but they have shown no influence on a 1 year's adherence degree 18 . Electronic pills monitoring devices may not be considered a friendly approach since they require regular visits to download data, and moreover, their size and cost may further limit their use 28–30 31 .…”

“…Importantly, QR code‐based scan is a feature that has already been used in other contexts and it could improve engagement if used within an m‐health app. However, recent results of small trials implementing m‐Health apps or more complex technologies have reported no direct improvement on medication adherence 30,32,33 . Nevertheless, all these studies suggest that the implementation of e‐Health in current medical practice may also boost the use of m‐Health technologies 34 …”

Adherence to Therapy: Burden, Complexity, and Perception

“…The better results obtained in the real life with intermittent therapies is due, at least in part, to the better adherence associated with a DOT strategy. In transplantation, simple strategies can help to improve adherence like health apps on smartphone that have been showed to reduce variability in tacrolimus trough concentrations 9 .…”