Immunosuppression regimens based on belatacept rather than cyclosporine are associated with better 7-year outcomes among kidney transplant recipients, according to final results from BENEFIT, a phase 3 study.
In that study, Flavio Vincenti, MD, of the University of California San Francisco, and colleagues randomly assigned 666 patients to receive a less-intensive or more intensive belatacept regimen or a cyclosporine regimen. Of these, 447 could be evaluated at 7 years: 163 in the less-intensive belatacept group, 153 in the more-intensive belatacept group, and 131 in the cyclosporine group.
Results showed a significant 43% reduction in the risk of death or graft loss in both of the belatacept treatment arms compared with the cyclosporine group, the investigators reported in The New England Journal of Medicine (2016;374:333-343). The less-intensive and more intensive belatacept groups had a significant 45% and 38% decreased risk of death, respectively, and a 41% and 44% decreased risk of graft loss, respectively, compared with the cyclosporine group.
In addition, the mean estimated glomerular filtration rate (eGFR) increased in patients in both belatacept groups but decreased in those treated with cyclosporine. From month 1 to month 84, patients in the less-intensive and more-intensive belatacept groups experienced mean eGFR increases of 1.39 and 130 mL/min/1.73 m2 per year, respectively, whereas the cyclosporine arm had a mean eGFR decline 1.04 mL/min/1.73 m2 per year.
The 3 treatment arms had similar cumulative frequencies of serious adverse events at 7 years.
The investigators acknowledged that a limitation of the trial was that it did not compare belatacept with tacrolimus, the current the standard-of-care calcineurin inhibitor, but patient and graft outcomes with contemporary tacrolimus-based regiments, they noted, are similar to those observed with cyclosporine-based regimens.
The study had originally enrolled 738 patients, of whom 666 underwent randomization to a treatment arm: 226 to a less-intensive belatacept regimen, 219 to a more-intensive belatacept regimen, and 221 to a cyclosporine-based regimen.
The less-intensive belatacept regimen consisted of 10 mg/kg of the medication on days 1 and 5 and at weeks 2 and 4 during month 0–1; 10 mg/kg at weeks 8 and 12 during months 2–3; and 5 mg/kg every 4 weeks beyond 3 months. The more-intensive belatacept regimen consisted of 10 mg/kg on days 1 and 5 and weeks 2, 4, 6, 8, 10, and 12 during months 0–3; 10 mg/kg at weeks 16, 20, and 24 during months 4–6; and 5 mg/kg every 4 weeks beyond month 6. The cyclosporine regimen consisted of an initial daily dose of 4–10 mg/kg, with the dose adjusted to 150–300 ng/mL during months 0–1. The dose was adjusted to 100–250 ng/mL beyond month 1.