Belatacept: a new biologic and its role in kidney transplantation.

Objective: To review the pharmacology, efficacy, safety, and role of belatacept in maintenance immunosuppression in adult kidney transplant recipients (KTR).

Data Sources: PubMed, EMBASE, International Pharmaceutical Abstracts, Web of Knowledge (1990-November 2011), and Google were searched using the terms belatacept, kidney or renal, and transplant.

Study Selection And Data Extraction: Relevant articles (English language and human subjects) were reviewed. Selected studies included 3 Phase 2 and 2 Phase 3 trials. Data were compared with Food and Drug Administration (FDA) briefing documents and belatacept full prescribing information.

Data Synthesis: Belatacept, a cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin, is the first marketed intravenous maintenance immunosuppressant. It is approved for use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids to prevent rejection in adult KTR. Belatacept exhibits linear pharmacokinetics and first-order elimination. The less intensive regimen used in Phase 3 trials is approved by the FDA. In low-moderate immunologic risk KTR, short-term patient and allograft survival appear comparable with that seen with cyclosporine, with improved renal function despite more frequent and severe early acute rejection. Preliminary data from Phase 2 corticosteroid-avoidance and conversion trials suggest that better renal function, acceptable rejection rates, and comparable patient and allograft survival may be achieved with belatacept compared with calcineurin inhibitors (CNIs). Common adverse effects of belatacept include anemia, neutropenia, urinary tract infection, headache, and peripheral edema. While a more favorable cardiovascular and metabolic profile and lack of requirement for therapeutic drug monitoring are attractive, a higher frequency of posttransplant lymphoproliferative disorder is concerning. Belatacept drug costs are significantly higher than those of standard CNI- or sirolimus-based regimens.

Conclusions: Belatacept provides a new option for maintenance immunosuppression in adult KTR. Further research is needed to compare its efficacy and safety with standard tacrolimus-based regimens, to evaluate whether increased drug costs are offset by long-term improvements in patient and allograft survival, and to establish its role in the immunosuppression armamentarium.