The two-year results from the three-year BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) and BENEFIT-EXT ("extended criteria") studies were presented Sunday at the American Transplant Congress in San Diego. A safety study that pooled long- term data also was presented.
In the BENEFIT trial, 666 patients were randomized to three groups and transplanted at 100 sites around the world, with 493 completing two years on treatment. In the BENEFIT-EXT study, 543 patients were randomized and transplanted, with 347 completing two years on treatment. The three treatment groups were less intensive (LI) and more intensive (MI) belatacept and a standard regimen of cyclosporine (CsA). All patients also received standard transplant regimens of the anti-T cell antibody basiliximab and drugs mycophenolate mofetil and corticosteroids.
Patient and graft survival after two years was similar among the belatacept and cyclosporine groups (94 percent MI; 95 percent LI; 91 percent CsA). The superior renal benefit of belatacept found after the first year of treatment was sustained in the second year, as measured by glomerular filtration rate. The improvement in cardiovascular/metabolic risk profile with belatacept remained in year two, with an additional beneficial effect noted in LDL cholesterol. Eight additional patients experienced an episode of acute rejection in year two (four with belatacept, four with cyclosporine), but in most cases this was successfully treated with drugs and did not lead to graft failure.
The overall incidence rate of malignancies and serious infections remained comparable across the groups. Although in the second year there remained a higher incidence of post-transplant lymphoproliferative disorder (PTLD)–five belatacept patients vs. one cyclosporine patient–the overall safety profile remained similar across the groups. No additional benefits were seen in the MI vs. the LI belatacept group.
"Our goal in transplantation is to achieve a normal life span for our patients, and to have them survive dialysis-free with a functioning transplanted organ for that life span," says Christian P. Larsen, MD, DPhil, director of the Emory Transplant Center and chair of the Department of Surgery in Emory University School of Medicine.
"Today, the median survival of a transplant remains about 8-10 years, far short of what we'd like," Larsen adds. "While the calcineurin inhibitors, cyclosporine and tacrolimus, are potent immunosuppressant drugs, they are associated with multiple toxicities that limit transplant success. We have been working for years to develop new therapies that avoid the main complications and causes of death, including cardiovascular events, infections and malignancies. Our data with belatacept indicate it can better preserve kidney function while improving the risk for these complications."
Larsen, along with fellow Emory University transplant surgeon and researcher Thomas C. Pearson, MD, DPhil, Emory professor of surgery and co-director of the kidney/pancreas transplant program at the Emory Transplant Center, made significant research contributions to the development of belatacept, in collaboration with other investigators at Emory, the Yerkes National Primate Research Center, and Bristol Myers Squibb.
A third study, which pooled safety data from phase II and phase III studies over 2.4 to 7 years, found that longer-term treatment with belatacept-based regimens was generally safe. The incidence of deaths and serious adverse events were lowest in the belatacept LI group. The overall incidence of malignancies remained low, but was slightly higher in the MI group. The incidence of herpes infections and tuberculosis (mostly in endemic areas) was low overall, but higher in the belatacept groups. Fifteen cases of PTLD occurred (13 with belatacept, 2 with cyclosporine), mainly in patients not previously exposed to Epstein-Barr virus, which many humans have as a low-level chronic infection. The researchers say PTLD might be reduced by avoiding use of belatacept in Epstein-Barr-naïve patients.
Belatacept is a "costimulation blocker" that inhibits one of two signals T cells require to trigger an immune response. It is a modified version of a fusion protein known as CTLA4-Ig, which mimics a regulatory molecule found on T cells and acts as a decoy. CTLA4-Ig (commercial name: abatecept/Orencis) is FDA approved to treat rheumatoid arthritis.
The clinical trials were sponsored by Bristol Myers Squibb. Dr. Larsen is an unpaid consultant to Bristol Myers Squibb on belatacept.
American Transplant Congress Abstracts (Embargoed until 7 p.m. ET, Sunday, May 4, 2010): Belatacept vs Cyclosporine in Kidney Transplant Recipients: Two-Year Outcomes from the BENEFIT Study: C.P. Larsen et.al.
Belatacept vs. Cyclosporine in ECD Kidney Transplants: Two-Year Outcomes from the BENEFIT-EXT Study: A. Durrbach, et.al.
Safety Profile of Belatacept in Kidney Transplant Recipients from a Pooled Analysis of Phase II and Phase III Studies: J. Grinyo, et.al.
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has $2.3 billion in operating expenses, 18,000 employees, 2,500 full-time and 1,500 affiliated faculty, 4,500 students and trainees, and a $5.7 billion economic impact on metro Atlanta.
Learn more about Emory's health sciences: http://emoryhealthblog.com - @emoryhealthsci (Twitter) - http://emoryhealthsciences.org
Kathi Baker | EurekAlert!
Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern
Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences