Evaluation of adherence and tolerability of prolonged‐release tacrolimus (Advagraf™) in kidney transplant patients in Germany: A multicenter, noninterventional study

Abstract

This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany.Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months. Composite primary endpoint: nonadherence at V4, defined as self-reported nonadherence on the Basel in medication), and treatment-related factors (eg, adverse events and duration of treatment). 7 In particular, kidney transplant recipients face the challenge of lifelong immunosuppressive medication.However, persistence with immunosuppressive medications after renal transplantation has been shown to decline over time, [8][9][10] with patients being more adherent in the early post-transplant period. 2Nonadherence to immunosuppressive treatment in renal transplant patients more than 1 year post-transplant is associated with an increased risk for late acute rejection during the following 5 years.2 Furthermore, the complexity of treatment regimens has been shown to negatively impact adherence to medication, with the probability of nonadherence increasing with dosing frequency. 11,12 A randomized, controlled multicenter trial using electronic monitoring of medication intake revealed that adherence to the assigned regimen was significantly higher with once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus (88.2% vs 78.8%, respectively; P = .0009). 12 However, long-term adherence data from | PATIENTS AND METHODS | Study design and patientsCOMET was accepted as a noninterventional study by the ethics committee and was conducted in accordance with the Declaration of Helsinki. Ethics committee approval was obtained, and all patients provided written informed consent. The study was registered in the public database of the Association of Research-based PharmaceuticalCompanies (Verband forschender Arzneimittelhersteller, VfA).The study included adult (≥18 years of age) kidney transplant recipients who received prolonged-release tacrolimus (Advagraf™;Astellas Pharma Europe BV, Leiden, Netherlands) either as first-line or as replacement antirejection prophylaxis for ≥1 month. There was no limit on time since transplantation and number of renal allografts previously received by the patient.During the 18-month observation period, data were recorded at baseline (Visit [V] 1), and at 6 (V2), 12 (V3), and 18 (V4) months (±2 weeks) postbaseline. At each visit, the following parameters were assessed: the laboratory parameters hemoglobin, serum creatinine, urine protein, and urine albumin; prolonged-release tacrolimus dose and trough levels; concomitant medication; rejection episodes and graft survival; dialysis dependence; vital signs (blood pressure and heart rate); and investigator/nurse assessment of adherence to prolongedrelease tacrolimus over the previous 4 weeks (rated "good," "moderate," or "poor"). Patients could also use ProMate, an electronic device that records the time of blist...

Evaluation of tools for annual capture of adherence to immunosuppressive medications after renal transplantation - a single-centre open prospective trial

“…Self‐reported nonadherence using BAASIS © in this population was 29% at 1‐year, which is in line with previous studies . As other reports also have shown , the majority of these NoAd patients took all the prescribed doses but had a time deviation (22%). A 2‐h time deviation as the BAASIS © form defines as nonadherence may seem rigid and its clinical relevance in RTxR has been questioned .…”

Tacrolimus Area Under the Concentration Versus Time Curve Monitoring, Using Home-Based Volumetric Absorptive Capillary Microsampling

“…As many of the developed tools do not evaluate the timing perspectives, an important aspect of immunosuppressive adherence is missing. BAASIS ® has established predictive validities the recent years and is today the most frequently used adherence questionnaire in transplant recipients (194,(202)(203)(204)(205)(206). BAASIS ® follow the recent ABC taxonomy of medication adherence (160), and assess adherence using items of dose taking, timing, drug holidays, drug reduction and discontinuation.…”

Posttransplant Medical Adherence: What Have We Learned and Can We Do Better?

“…Nevertheless, some new evidence suggests that moving from twice-daily to once-daily dosing of the mainstay of the immunosuppressive regimen, the calcineurin inhibitor, may ultimately shift non-adherence prevalence rates downward. Thus, following on a randomized clinical trial (RCT) demonstrating better adherence with once-daily tacrolimus dosing [9••], Lehner et al [10•] reported on a multisite longitudinal observational study of patients receiving once-daily dosing of tacrolimus. They found self-reported non-adherence rates of between 9 and 13% during the month before each study assessment time point (through a maximum of 18 months of follow-up).…”

“…In heavily studied components of the medical regimen (e.g., immunosuppression medication-taking), the added value of new studies documenting prevalence rates is likely to be small. Exceptions would be longitudinal observational studies, like the work of Lehner et al [10•], which focus on examining non-adherence rates among programs that adopted empirically supported adherence promotion strategies. However, for any new studies, it would be important to reconsider the cut points traditionally used to identify non-adherent patients.…”