June 5, 2009 (Boston, Massachusetts) — A phase 3 study of belatacept vs cyclosporine (CsA) shows that at 1 year, belatacept appears to be associated with better preservation of renal function and structure in kidney transplantation.

Here at the American Transplant Congress 2009: The Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation, researchers from the University of Barcelona, Spain, presented findings from their subanalysis of the BENEFIT study comparing the 2 agents.

Posttransplant renal function at 1 year and chronic allograft nephropathy (CAN) correlate with long-term graft function and patient/graft survival, according to the study abstract.

"Long-term patient and graft survival has not improved over the last decade, despite decreased rejection rates," said study investigator Josep Maria Grinyó, MD, who presented the findings.

"Renal function is an important determinant of long-term outcomes, and [CAN] is a leading cause of late graft loss," he added.

Possibility of Long-Term Maintenance

The BENEFIT trial included 666 patients randomly assigned to 3 treatment groups: more intensive (MI) belatacept (n = 219), less intensive (LI) belatacept (n = 226), and CsA (n = 221).

Measurement of the primary endpoint — composite renal impairment — showed that patients in both belatacept groups had improved renal function compared with patients in the CsA group (CsA, 78%; MI, 55%; LI, 54%; P < .001 each belatacept group vs CsA).

Glomerular filtration rates (GFRs) were higher by 13 to 15 mL in both belatacept groups at month 12. At 1 year, the mean measured GFR was 65 mL/min in the MI group, 63 mL/min in the LI group, and 50 mL/min in the CsA group (P < .0001 each belatacept group vs CsA).

Similarly, the mean calculated GFR using the Modification of Diet in Renal Disease formula was 68 mL/min/1.73 m2 in the MI group, 68 in the LI group, and 54 in the CsA group (P < .0001 for each belatacept group vs CsA).

The prevalence of CAN at 12 months was lower in both belatacept groups (MI, 18%; LI, 24%; CsA, 32%; P = .001 for MI vs CsA; P = .058 for LI vs CsA).

"The impact on medical practice may be that for the first time, we'll be able to maintain our patients long-term without taking the classical calcineurin inhibitor [CNI], which has been considered the cornerstone of immunosuppression," Dr. Grinyó told Medscape Transplantation. "The concept is that to keep renal function, we have to inhibit T-cell activation. CNIs, like cyclosporine, do that very well, but this agent is also able to do that."

Unique Regimen

According to Dr. Grinyó, the BENEFIT study regimen is unique because it uses a costimulatory blocker for both induction and maintenance therapy. "Originally, biological agents were used only for induction. This allows for a CNI-free regime in the long-term with a better preservation of renal function and an improved cardiovascular risk profile," he said.

Asked by Medscape Transplantation to comment on the findings, Todd Pesavento, MD, from the Ohio State University College of Medicine, Columbus, said the study result was not unexpected, as other studies with belatacept regimens have shown largely similar results.

"[The investigators] did show less chronic allograft nephropathy at 1 year, and that, in the long term, may portray a better...renal outcome. One thing that was surprising to me was [that] the low-intensity belatacept group had a higher rate of chronic allograft nephropathy numerically, although it may not be statistically important," said Dr. Pesavento.

The study was sponsored by Bristol-Myers Squibb. Dr. Grinyó has served as an advisor to Bristol-Myers Squibb in the past. Dr. Pesavento has disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2009: The Joint Annual Meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST): Abstract 236. Presented June 1, 2009.

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