Prolonged-Release vs Immediate-Release Tacrolimus Capsules in Black vs White Kidney Transplant Patients: A Post Hoc Analysis of Phase III Data.

Background: Black kidney transplant patients experience inferior outcomes compared with other ethnicities. Because scrutiny is required when immunosuppressant drugs are used in such at-risk populations, we report the first large-scale clinical efficacy data assessing prolonged-release tacrolimus (PR-T) in black de novo kidney transplant patients.

Methods And Materials: We used logistic regression and proportionate hazards to compare a composite outcome measure (biopsy-proven acute rejection, graft loss, mortality, and loss to follow-up) in black and white patients in treatment groups longer than 24 weeks, from 3 large Phase III randomized controlled trials. Secondary endpoints included tacrolimus trough concentration, dose, and estimated glomerular filtration rate.

Results: The study included 2162 patients whose treatments belonged to two categories (immediate-release tacrolimus: 77 black patients, 721 white patients; and PR-T: 87 black patients, 1277 white patients). Despite demographic factors generally predictive of worse outcomes, efficacy failure among black patients who received PR-T was non-inferior to that among white patients who received either therapy. Compared with immediate-release tacrolimus, black patients who received PR-T achieved stable tacrolimus concentrations 2.5 times faster (21 vs 56 days, P = .04), and more achieved stable target concentrations (76.7% vs 69.3%). Treatment-emergent adverse events were consistent with those reported separately in pivotal trials.

Conclusions: Overall, black patients who received PR-T achieved non-inferior outcomes compared to white patients, despite higher pretransplant risk among black patients. Moreover, PR-T improved the time to achieve, and the likelihood of reaching, stable therapeutic concentrations among black patients, suggesting that PR-T could improve the consistency of tacrolimus exposure in this patient population.