Impact of Once- Versus Twice-Daily Tacrolimus Dosing on Medication Adherence in Stable Renal Transplant Recipients: A Canadian Single-Center Randomized Controlled Trial

Abstract

Background: Prevalence of immunosuppressant nonadherence in renal transplant recipients is high despite negative clinical outcomes associated with nonadherence. Simplification of dosing has been demonstrated to improve adherence in renal transplant recipients as measured through electronic monitoring and self-report. Objective: The purpose of this study was to replicate and extend previous findings by measuring adherence with multiple methods in a Canadian sample. Design: The study design was a randomized controlled medication dosing trial in adult renal transplant patients. The trial length was 4 months. Setting: This study was conducted within the Solid Organ Transplant (SOT) Clinic at Vancouver General Hospital (VGH; Vancouver, Canada). Patients: A total of 46 adult renal recipients (at least 1 year post-transplant) were recruited through the SOT clinic. With 8 withdrawals, 38 individuals completed all phases of the study. Measurements: Medication adherence was measured for a period of 4 months using multiple methods, including electronic monitoring (MEMS [Medication Event Monitoring System]), pharmacy refill data (medication possession ratio [MPR]), and by self-report using the Adherence subscale of the Transplant Effects Questionnaire (TEQ). Methods: Participants were randomized to twice-daily (n = 19) or once-daily tacrolimus dosing (n = 19) and followed over a 4-month period via monthly clinic study visits. Comparisons between the treatment groups were performed using the Mann-Whitney U and chi-square tests, for continuous and categorical variables, respectively. Results: As outlined in Table 3, the once-daily dosing group showed significantly better MEMS Dose Adherence ( P = .001), whereas MEMS Timing Adherence showed a tendency toward better adherence for this group, but was not significant ( P = .052). MEMS Days Adherent ( P = .418), MPR% ( P = .123), and self-reported adherence ( P = .284) did not differ between the once- and twice-daily dosing groups when measured as continuous variables. The MPR% was significantly better for the once-daily dosing group when measured dichotomously but not continuously ( P = .044). Notably, most of those exposed to once-daily dosing (63.2%) preferred this to the twice-daily regimen. Limitations: Limitations included small sample size and short follow-up period, precluding the examination of clinical outcome differences. Conclusions: Results for dose adherence replicate the finding that dose simplification increases adherence to immunosuppressants as measured through electronic monitoring. Such an advantage for the once-daily dosing group was not seen across the 2 other electronic monitoring measurement variables (days and timing adherence). This study extends previous research by examining adherence in once versus twice-daily dosing via prescription refill data in a Canadian sample. Given the gravity of potential health outcomes associated with nonadherence, although results indicate inconsistencies in significance testing across measurement methods, the medium to large effect sizes seen in the data favoring better adherence with once-daily dosing provide an indication of the potential clinical significance of these findings. Trial registration: This study was registered with ClinicalTrials.gov (NCT01334333) on April 11, 2011.

Determinants of disease acceptance in renal transplantation patients assessed with the application of Acceptance Illness Scale (AIS)

“…Their lifestyle, social roles and concepts of the world and identity are revised. The patient's attitude towards the disease also influences the active involvement in the therapy process by adherence to the appropriate frequency and time of taking medications, controlling their undesirable effects, and noting interactions (16). Therefore, it was justified to undertake the research to assess the degree of acceptance and identify the factors determining this parameter in renal transplant recipients, since the available literature has little data on this subject, and the obtained results may significantly optimize patient care.…”

From Nonadherence to Adherence

“…A recent smaller randomized single-center study (n=38) using several adherence measurement methods confirmed better MEMS dose adherence (p=0.001) with the once-daily formulation of tacrolimus and a tendency toward better timing adherence (p=0.052) after 4 months. 65 MEMS day adherence and self-reported adherence (Transplant Effects Questionnaire, TxEQ) did not differ between formulations whereas medication possession ratio (MPR%) was significantly better in the QD group when measured dichotomously (p=0.044). 65 Other, uncontrolled or nonrandomized studies confirmed improvement in medication adherence in kidney, liver and heart transplant recipients after switching from a BID formulation to a QD formulation of tacrolimus.…”

“…65 MEMS day adherence and self-reported adherence (Transplant Effects Questionnaire, TxEQ) did not differ between formulations whereas medication possession ratio (MPR%) was significantly better in the QD group when measured dichotomously (p=0.044). 65 Other, uncontrolled or nonrandomized studies confirmed improvement in medication adherence in kidney, liver and heart transplant recipients after switching from a BID formulation to a QD formulation of tacrolimus. [66][67][68][69] All these studies measured adherence uniquely by using self-report questionnaires (eg, BAASIS and others) but without electronic monitoring.…”

Glycol chitosan-based tacrolimus-loaded nanomicelle therapy ameliorates lupus nephritis

“…However, clinical management with TAC therapy remains challenging due to its narrow therapeutic range and off-target effects on other organs, as well as the negative effect of long-term TAC use, including neurotoxicity, new-onset diabetes, and nephrotoxicity [ 15 , 16 ]. In addition, the twice-daily oral administration decreased patient adherence to TAC therapy [ 17 ]. Although new extended-release TAC formulations exist, TAC needs to be administered daily, and the trough level for maintaining optimal therapeutic targeting should be checked [ 18 ].…”