Comparing renal transplant patients’ adherence to free cyclosporine and free tacrolimus immunosuppressant therapy

113

105

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A doubleblind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval −7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelvemonth patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.

Section: Prograf (Astellas Pharma Europe Ltd Staines Uk; Hereafter mentioning

confidence: 99%

Once‐Daily Prolonged‐Release Tacrolimus (ADVAGRAF) Versus Twice‐Daily Tacrolimus (PROGRAF) in Liver Transplantation

Trunečka

Boillot

Seehofer³

et al. 2010

113

105

“…In the first study, when adult RTRs were responsible for paying for their IST, those who took cyclosporine were more adherent than those who took tacrolimus (37); however, when IST was provided at no cost, the opposite was found--those RTRs taking tacrolimus were more adherent than those taking cyclosporine (38 …”

Section: Additionally the Findings Of Previous Studies Of Age And Ismentioning

confidence: 99%

Immunosuppressant Therapy Adherence and Graft Failure Among Pediatric Renal Transplant Recipients

Chisholm-Burns

Spivey

Rehfeld

et al. 2009

The study objective was to determine the association between immunosuppressant therapy (IST) adherence and graft failure among pediatric renal transplant recipients (RTRs) using data reported in the United States Renal Data System (USRDS), which contains Medicare prescription claims. RTRs (≤18 years) who received their only transplant during 1995-2000, experienced graft survival more than 6 months posttransplant, had 36 months of USRDS data (or had data until graft failure or death), utilized Medicare IST coverage, and were prescribed cyclosporine/tacrolimus were included. IST adherence was measured by medication possession ratio (MPR). Cox proportional hazards analysis was used to assess the relationship between time to graft failure and continuous MPR. MPR quartiles were used to examine MPR as a categorical variable (Quartile 4 = adherent group, Quartiles 1-3 = nonadherent group). Kaplan-Meier estimates of time to graft failure were compared between adherent and nonadherent groups. 877 RTRs met inclusion criteria. Cox proportional hazards modeling suggested that greater adherence was significantly associated with longer time to graft failure (p = 0.009), after adjusting for relevant clinical factors. Kaplan-Meier analysis found a difference between adherent and nonadherent groups in graft survival by time (v 2 = 5.68, p = 0.017). Interventions promoting adherence should be implemented among pediatric RTRs and parents/guardians to optimize graft survival.

“…Nonadherence is a major cause of preventable graft loss (1)(2)(3). Interventions that improve treatment adherence, such as morning dosing and reducing administration frequency (4,5), may also improve longterm outcomes (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in De Novo Renal Transplantation: A Randomized Phase III Study

Krämer

Charpentier

Bäckman

et al. 2010

162

135

This multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. A doubleblind, double-dummy 24-week period was followed by an open extension of up to 12 months posttransplant. Biopsy-proven acute rejection rate at 24 weeks (primary endpoint, per-protocol analysis) was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment difference 4.5%, 95% confidence interval--1.8%, 10.9%, just outside the prespecified 10% noninferiority margin). Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. Both treatment groups showed equally wellmaintained renal function at 12 months (mean creatinine clearance approximately 67 mL/min) and similar adverse event profiles. Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation.