A comparative study of once-daily vs twice-daily tacrolimus in deceased donor kidney transplant recipients: a national cohort analysis

The comparative real-world effectiveness of extended-release (Life Cycle Pharma tacrolimus [LCPT]) vs immediate-release (IR) tacrolimus formulations in deceased-donor kidney transplantation remains incompletely characterized. We conducted a national retrospective cohort study of adult deceased-donor kidney transplant (DDKT) recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry (January 1, 2018-June 30, 2023) discharged on tacrolimus plus mycophenolate. Multiorgan and living-donor transplants, and recipients who switched formulations during the index hospitalization, were excluded. Exposure was the tacrolimus formulation at discharge (IR-brand, IR-generic, or LCPT). The prespecified primary outcome was all-cause graft failure (ACGF), evaluated using inverse probability of treatment weighting-adjusted Cox models. Among 79 833 recipients, LCPT (n = 11 581) was associated with a lower adjusted hazard of ACGF than IR-brand tacrolimus (hazard ratio [HR], 0.877; 95% confidence interval [CI], 0.797-0.965), whereas IR-generic and IR-brand did not differ (HR, 0.939; 95% CI, 0.868-1.016). The association was consistent in a sensitivity analysis restricted to centers prescribing all 3 formulations (HR, 0.872; 95% CI, 0.789-0.963) and in a propensity-score-matched analysis comparing LCPT with combined IR tacrolimus (HR, 0.913; 95% CI, 0.836-0.998). In this national deceased-donor kidney transplant cohort, LCPT was associated with a modestly lower adjusted risk of ACGF relative to IR tacrolimus.