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University of Cincinnati leads first trial on steroid and CNI withdrawal post-transplant

2012-11-28
(Press-News.org) CINCINNATI—The University of Cincinnati will lead a $5.2 million national trial studying removal of both corticosteroids and common immunosuppression treatments from the post-transplant drug regimen for kidney transplant patients.

The Belatacept Early Steroid withdrawal Trial (BEST) seeks to determine if a belatacept-based regimen for post-transplant patients can prevent organ rejection without the harmful side effects posed by corticosteroids and calcineurin inhibitor (CNI) immunosuppressants. Belatacept is a modified version of the drug abatacept, which is used to treat rheumatoid arthritis.

Led by principal investigator and director of UC's division of transplantation E. Steve Woodle, MD, the $5.2 million trial will be carried out at four other transplant centers across the country: University of Wisconsin, University of Minnesota, California Pacific Medical Center and the Christ Hospital in Cincinnati.

The BEST study is the first large, multicenter trial to remove both corticosteroids and CNIs from a patient's drug regimen after kidney transplantation. Both drugs place patients at an increased risk of cardiovascular disease, high blood pressure, high cholesterol and diabetes. Additionally, CNIs have shown toxicity to transplanted kidneys.

"Cardiovascular events like stroke and heart attacks are the top cause of death for both the general population and transplant patients," says Woodle, who also serves as William A. Altemeier Chair in the UC Department of Surgery. "We've previously demonstrated that early steroid withdrawal results in reduced rates of rejection and increased graft survival in transplant patients."

Rita Alloway, PharmD, research professor of medicine and director of transplant clinical research within the UC Department of Internal Medicine, will direct the coordinating center for the trial. She says belatacept was approved by the Food and Drug Administration in 2011 for prevention of rejection in kidney transplant patients—the first FDA-approved drug to replace CNIs like tacrolimus and cyclosporine.

"This trial is a major step forward in immunosuppression because it provides a means to avoid many of the toxicities of the CNI drugs, particularly kidney toxicity, high blood pressure, and hyperlipidemia," says Alloway.

Adele Shields, PhD, associate research professor of surgery with clinical practice at the Christ Hospital, has specialized in quantitating the impact of long-term immunosuppression on cardiac risk factors and cardiac events.

"An important feature of the belatacept-based treatment regimen is that it provides an opportunity to greatly minimize cardiovascular risk in the long term," she says. "By avoiding both CNIs and corticosteroids, this trial provides an opportunity to substantially impact long-term patient survival following kidney transplantation."

### The trial seeks to enroll 315 new kidney transplant patients across all centers. Enrollment will begin December 2012.


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[Press-News.org] University of Cincinnati leads first trial on steroid and CNI withdrawal post-transplant