Belatacept – An Alternative to Cyclosporine in Kidney Transplant Patients

People who undergo organ transplantation are always at a risk that their immune system may recognize the transplanted organ as foreign and launch an attack against it. This may result in graft failure, thereby making the entire transplantation process futile. To prevent this, following transplantation, patients are put on medications to suppress immunity. These medications are called immunosuppressant drugs. They have their own side effects, and make the patient prone to repeated and even life-threatening infections.

A commonly used immunosuppressant drug following kidney transplantation is cyclosporine. Though its benefits have been established, cyclosporine does have side effects like cardiovascular diseases and diabetes. Also, over time, kidney function could reduce with the medication.

Belatacept is a new immunosuppressant drug that was approved by the FDA and the Europeans Medicines Agency in 2011 for use in kidney transplant patient. Available as Nulojix, it appears to several benefits over cyclosporine, as demonstrated by a 7-year clinical trial recently published in the New England Journal of Medicine.

The BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) study compared the efficacy and safety of three regimens, an intensive belatacept-based regimen, a less intensive belatacept-based regimen, and a cyclosporine-based regimen taken for 7 years following kidney transplantation. All the patients in the study also received basiliximab, mycophenolate mofetil, and glucocorticoids.

The researchers found that:

• The risk of death or graft rejection at 7 years was almost half in patients on belatacept, compared to those on a cyclosporine-based regimen.
• Kidney function as measured by eGFR (Estimated Glomerular Filtration Rate) was found to be reduced in patients taking cyclosporine, but improved slightly in patients taking belatacept.
• Acute rejection was more common with the belatacept group as compared to the cyclosporine group.
• The side effect of post-transplant lymphoproliferative disorder (PTLD) was more common with the belatacept groups. PTLD is a type of malignant condition where the body produces excess immune cells called lymphocytes. Researchers had earlier reported that this side effect may occur in individuals taking belatacept who had Epstein- Barr virus infection.
• The development of donor-specific antibodies was less in the belatacept-based regimens as compared to the cyclosporine-based regimen. These antibodies can result in rejection of the kidney tissue.

Cyclosporine is taken orally while belatacept has to be injected by the healthcare provider. Though the injections may be inconvenient to the patient, the patient is less likely to skip a dose with this regimen. This will ensure lesser chances of rejection of the donor organ.

Though belatacept has been found to be a better choice than cyclosporine in the maintenance treatment of kidney transplant, the researchers admit that a comparison with tacrolimus, another immunosuppressive drug used in the prevention of kidney rejection, could provide a better picture of the usefulness of this medication. Also, the prohibitive cost of belatacept could be a deterrent to a large number of patients who could benefit from its use.

References:

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1. Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal M, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche H, Munier, S, Larsen CP. Belatacept and Long-Term Outcomes in Kidney Transplantation N Engl J Med 2016; 374:333-343 DOI: 10.1056/NEJMoa1506027

Source-Medindia