Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy

Abstract

Background: Belatacept is a novel immunosuppressive therapy designed to improve clinical outcomes associated with kidney transplant recipients while minimizing use of calcineurin inhibitors (CNIs). Methods: We searched for clinical trials related to administration of belatacept to kidney transplant patients compared to various immunosuppression regimens, as well as for studies that utilized data from belatacept trials to validate new surrogate measures. The purpose of this review is to consolidate the published evidence of belatacept's effectiveness and safety in renal transplant recipients to better elucidate its place in clinical practice. Results: Analysis of the results from the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppressive Trial (BENEFIT) study, a de novo trial that compared cyclosporine (CsA)-based therapy to belatacept-based therapy in standard criteria donors, found a significant difference in mean estimated glomerular filtration rate (eGFR) of 13-15 mL/ min/1.73 m 2 and 23-27 mL/min/1.73 m 2 at 1 year and 7 years, respectively. The BENEFIT-EXT study was similarly designed with the exception that it included extended criteria donors. Renal function improved significantly for the more intensive belatacept group in all years of the BENEFIT-EXT study; however, it was not significant in the less intensive group until 5 years after transplant. Belatacept regimens resulted in lower blood pressure, cholesterol levels, and incidence of new-onset diabetes after transplant compared to CsA-based regimens. Results from conversion of CNIs to belatacept therapy, dual therapy of belatacept with sirolimus, and belatacept with corticosteroid avoidance therapy are also included in this article. Conclusion:The evidence reviewed in this article suggests that belatacept is an effective alternative in kidney transplant recipients. Compared to CNI-based therapy, belatacept-based therapy results in superior renal function and similar rates of allograft survival. In terms of safety, belatacept was shown to have lower incidence of hypertension, hyperlipidemia, and diabetes; however, incidence of posttransplantation lymphoproliferative disorder and the cost of belatacept may hinder use of this medication.

Belatacept conversion in adolescent and young adult kidney transplant recipients

“…Studies in adults have demonstrated improvement in eGFR several years post conversion. 5 This case series shows that conversion from TAC to BELA immunosuppression in adolescents and young adults is safe and effective, as evidenced by maintenance of stable graft function and no increase in infections, hospitalizations, AR, dnDSA formation, or viral replication. These results need to be validated in larger conversion studies.…”

Basiliximab as maintenance immunosuppression in heart transplant recipients: A single pediatric center experience

“…However, infection was a common complication (33.3%), and 19% of patients discontinued therapy due to adverse effects 16 . Belatacept is contraindicated in patients who have an unknown EBV status or are EBV seronegative due to significantly increased risk of developing PTLD 17 . Notably, our patient cohort included 2 patients with chronic EBV viremia and 1 additional patient with a history of PTLD.…”

“…16 Belatacept is contraindicated in patients who have an unknown EBV status or are EBV seronegative due to significantly increased risk of developing PTLD. 17 Notably, our patient cohort included 2 patients with chronic EBV viremia and 1 additional patient with a history of PTLD. While receiving BAS, a third patient developed asymptomatic EBV viremia, and 1 patient was diagnosed with non-destructive PTLD of the tonsils; neither had disease progression on BAS therapy.…”

Penggunaan Produk Biosimilar pada Transplantasi Ginjal

“…11 Gambar 2. Mekanisme kerja belatacept12 Gambar 3. Milestone penelitian belatacept12 ANALISISpaling sering ditemukan adalah anemia, neutropenia, diare, sakit kepala, dan edema perifer.…”

“…Mekanisme kerja belatacept12 Gambar 3. Milestone penelitian belatacept12 ANALISISpaling sering ditemukan adalah anemia, neutropenia, diare, sakit kepala, dan edema perifer. Belatacept juga dikaitkan dengan risiko peningkatan terjadinya posttransplantation lymphoproliferative disorders (PTLD), yang terutama terjadi pada 18 bulan setelah transplantasi.…”