New drug for kidney transplant recipients effective in humans

February 17, 2010

Initial results of a study conducted at 100 centers worldwide indicate that belatacept, a first-in-class costimulation blocker can prevent the immune system rejecting new organs. The results also suggest that it may provide similar patient and graft survival to cyclosporine but with fewer side effects and superior kidney function after 12 months. The study, published today in the American Journal of Transplantation, provides the first findings to come from BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial).

Although advances in transplantation have reduced rates of organ rejection and improved outcomes after one-year, corresponding improvements in long-term survival rates have not been observed. The kidney allograft (transplant from another human donor with different genes) survival rate is 95% for transplants from living donors and 89% for transplants from deceased donors during the first year. BENEFIT is a three-year, randomized, active-controlled, parallel-group, set up to evaluate the efficacy of belatacept for post-transplant maintenance immunosuppressive management.

"Our findings show that this will be a novel and more specific way of suppressing the immune system with less toxicity," said lead researcher Dr. Flavio Vincenti, of the University of California, San Francisco Medical Center. "It will target the specific responses that cause rejection of transplanted organs with less damage to other systems of the body."

Belatacept is different from calcineurin inhibitors (CNI), such as cyclosporine, which is the class of drugs most commonly used to suppress the immune system in transplant patients, because it does not cause the toxicities associated with CNI - such as nephrotoxicity and aggravating cardiovascular risk factors. Belatacept selectively blocks T-cell activation (which plays a key part in immune response) and the results suggest that this selectivity allows effective immunosuppression, better preservation of renal function and an improved cardiovascular/metabolic risk profile.

The researchers found that treatment with belatacept was generally safe, although there was a higher incidence of post-transplant lymphoproliferative disorder in belatacept patients with known risk factors.

686 patients 18 years or older who were expected to receive a kidney transplant from a standard criteria donor were included in BENEFIT, and were randomized into three groups; more or less intensive regimens of belatacept, or cyclosporine. 666 patients eventually received a transplant and of these, 527 patients completed the initial 12 month treatment phase, with an even spread of discontinuation between the groups.

"Although belatacept was associated with a higher early rejection rate than patients treated with cyclosporine, it was also associated with better kidney function and thus has the potential of extending the life of the renal graft," added Vincenti. "Of course, only time will tell how many patients may benefit from this new drug."

Alongside the BENEFIT study is BENEFIT-EXT, which included 543 recipients of extended criteria donors (defined as donors over 60 years old, over 50 years and with two other risk factors, or donation after cardiac death, or more than 24 hours with no blood supply to the organ). 394 patients completed the initial 12 months of this trial with similar results. The initial results of this study are also published today in the American Journal of Transplantation.
-end-


Wiley

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.