Belatacept, sold under the brand name Nulojix, is a prescription medication used to prevent organ rejection in adults following a kidney transplant. As a selective T-cell costimulation blocker, it is a type of immunosuppressant that dampens the body’s immune response to prevent it from attacking the new organ. This medication is specifically for kidney transplants and not approved for other organ types.
Mechanism of Action
To understand how belatacept functions, it is helpful to visualize the immune system as a security team protecting the body. When a new kidney is transplanted, this team identifies it as an unfamiliar presence. A specific type of immune cell, the T-cell, is a primary actor in coordinating the response against the new organ. For these T-cells to become fully activated and launch an attack, they require two distinct signals from other immune cells called antigen-presenting cells (APCs).
The first signal occurs when the T-cell recognizes a piece of the foreign organ. This initial alert is not enough on its own to trigger a full-scale immune reaction. A second confirmation signal, known as costimulation, is also needed. This second signal involves the interaction between proteins on the T-cell surface, called CD28, and proteins on the APCs, named CD80 and CD86. Without this second interaction, the T-cell does not become fully activated.
Belatacept works by selectively interrupting this second step. It is a fusion protein that binds to the CD80 and CD86 proteins on the APCs. By occupying these sites, belatacept physically blocks them from connecting with the CD28 proteins on the T-cells. This action prevents the T-cells from receiving the necessary second signal, which stops their activation and proliferation. The result is a more targeted calming of the immune response against the transplanted kidney, rather than a broad suppression of the entire immune system.
Use in Kidney Transplant Recipients
Belatacept is approved for preventing organ rejection in adult kidney transplant patients. It is not a standalone treatment but is integrated into a broader immunosuppressive regimen that includes an induction agent like basiliximab, an antimetabolite such as mycophenolate mofetil (MMF), and corticosteroids. This multi-drug approach targets different immune system pathways.
The administration of belatacept is done through an intravenous (IV) infusion in a hospital or clinic setting, a process that takes about 30 minutes. The dosing schedule is structured in two distinct phases. The initial phase involves more frequent infusions to establish stable drug levels, with a 10 mg/kg dose given on the day of transplant, on day five, and at the end of weeks two, four, eight, and twelve.
Following this initial period, the patient transitions to a maintenance phase. This long-term phase involves a lower dose of 5 mg/kg administered once every four weeks. The dosage is calculated based on the patient’s body weight at the time of the transplant. This structured dosing ensures the immune system remains sufficiently suppressed to protect the new kidney.
Key Differences from Calcineurin Inhibitors
A major distinction of belatacept is its comparison to an older class of immunosuppressants called calcineurin inhibitors (CNIs), like tacrolimus and cyclosporine. A significant drawback of long-term CNI use is their potential for nephrotoxicity, meaning they can damage the kidneys over time. Belatacept was developed as an alternative to provide immunosuppression while helping to preserve long-term kidney function.
Clinical studies have shown that patients treated with belatacept often have better kidney function, measured by the glomerular filtration rate (GFR), compared to those on CNI-based regimens. This preservation of renal function is a primary advantage. Belatacept generally has a more favorable profile regarding certain metabolic side effects. Patients may have a lower incidence of new-onset diabetes after transplant and better blood pressure control.
While offering these benefits, belatacept regimens can be associated with a higher rate of early acute rejection episodes compared to CNI-based therapies. These rejection events often occur within the first year and are typically treatable. Despite this, long-term studies indicate that patient and graft survival rates are comparable or better with belatacept, suggesting the initial risk does not compromise the long-term success of the transplant.
Associated Risks and Safety Information
Belatacept carries a boxed warning from the FDA, the most serious type, for an increased risk of Post-Transplant Lymphoproliferative Disorder (PTLD), a type of cancer affecting the lymphatic system. This risk is substantially higher for patients who are Epstein-Barr Virus (EBV) seronegative, meaning they have never been exposed to EBV. For this reason, belatacept is contraindicated and should only be used in patients who are EBV seropositive.
As with all immunosuppressive therapies, treatment with belatacept increases the risk of serious infections and other malignancies, including skin cancer. Patients are more susceptible to opportunistic infections because their immune defenses are lowered to prevent organ rejection. It is recommended that individuals on belatacept limit exposure to sunlight and UV light by using protective clothing and sunscreen.
Another serious, though rare, risk is Progressive Multifocal Leukoencephalopathy (PML), a rare brain infection that can lead to severe disability or death. Any new or worsening neurological or cognitive symptoms should be reported to a healthcare provider immediately. These warnings underscore the importance of careful patient selection and monitoring by a specialized transplant team.