Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial

Background: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. Study Design: 36-month follow-up of the intention-to-treat population. Setting & Participants: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [ GFR], 35-75 mL/min/1.73 m(2)). Interventions: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n 5 84) or continue CNI-based therapy (n 5 89). Outcomes: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. Measurements: Treatment exposure2adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. Results: Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure2adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07 mL/min/1.73 m(2) per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P = 0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P = 0.9). Limitations: Exploratory post hoc analysis with a small sample size. Conclusions: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons. org/licenses/by-nc-nd/4.0/).