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!
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy