Session Time: 3:15pm-4:45pm
Presentation Time: 4:03pm-4:15pm
*Purpose: To compare, using an adaptive study design, the 1-year incidence of a novel two-part composite endpoint consisting of de novo donor-specific antibody (dnDSA) formation and/or immune activation (IA) in kidney transplant (Ktx) recipients maintained on extended- (ERT) vs immediate-release tacrolimus (IRT).
*Methods: In this exploratory, prospective, multicenter, randomized, open-label trial (NCT02723591), 599 adult Ktx recipients were randomized 1:1 to receive once daily ERT (Astagraf XL®, Astellas Pharma US, Inc.) or twice daily IRT maintenance immunosuppression with corticosteroids and mycophenolate mofetil (target tacrolimus trough concentration ≥6 ng/mL). Positivity for dnDSA was defined as MFI >1000. IA was defined as a positive peripheral blood molecular signature as measured by the Trugraf™ v2.0 molecular assay (Transplant Genomics, Inc., USA). The difference in the proportion of patients meeting the primary composite endpoint was assessed by testing the null hypothesis of no treatment effect (H0: odds ratio [OR]=1; multivariable logistic regression analysis).
*Results: Safety was analyzed in 575 and efficacy in 554 patients (confirmed DSA negative at time of tx; ERT, n=275; IRT, n=279). By Day 365, incidence of the novel primary composite endpoint (dnDSA and/or IA) was 35.6% in the ERT group vs 34.4% in the IRT group (Table). Adjusted OR for ERT vs IRT was 1.12 (95% CI: 0.76, 1.64; p=0.58). Incidence of the traditional four-part composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up was 9.1% vs 10.4%, respectively. Mean relative improvements in eGFR from Day 30 to Day 365 were 19.7% for ERT and 20.8% for IRT (respective mean increase, 6.04 vs 6.39 mL/min/1.73 m²). Mean eGFR at Day 365 was 58.25 vs 60.86 mL/min/1.73 m². BK virus was reported in 15.6% and 12.9% of patients, respectively. No unexpected safety findings were reported.
*Conclusions: This is the first large-scale RCT in the field of solid organ tx to use potential biomarkers as the primary outcome measure. At 1 year post tx, incidence rates of dnDSA formation and BPAR were similar with ERT and IRT. dnDSA rates were lower than historically reported. Both tacrolimus formulations yielded 1-year death-censored graft survival >98% under contemporary US practice conditions.
To cite this abstract in AMA style:Wiseman A, Kaufman D, Patel A, Wojciechowski D, Tambur A, Kim J, Schwartz J. Impact of Extended- versus Immediate-Release Tacrolimus on One-Year Development of De Novo DSA and Chronic Immune Activation in Kidney Transplantation (ASTOUND Study) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-extended-versus-immediate-release-tacrolimus-on-one-year-development-of-de-novo-dsa-and-chronic-immune-activation-in-kidney-transplantation-astound-study/. Accessed September 29, 2020.
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