Recent trials in immunosuppression and their consequences for current therapy

被引:4
作者
Wohlfahrtova, Mariana [1 ,2 ]
Viklicky, Ondrej [1 ,2 ]
机构
[1] Inst Clin & Expt Med, Dept Nephrol, Transplant Ctr, Prague 14021 4, Czech Republic
[2] Inst Clin & Expt Med, Transplant Lab, Prague 14021 4, Czech Republic
关键词
biomarker-driven immunosuppression; calcineurin inhibitor; cell therapy; costimulation blockade; kidney transplantation; NOVO KIDNEY-TRANSPLANTATION; TWICE-DAILY TACROLIMUS; ALLOREACTIVE T-CELLS; PHASE-III; MAINTENANCE IMMUNOSUPPRESSION; THROMBOTIC MICROANGIOPATHY; MYCOPHENOLATE-MOFETIL; RENAL-TRANSPLANTATION; ALEMTUZUMAB INDUCTION; GENERIC TACROLIMUS;
D O I
10.1097/MOT.0000000000000093
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review Although the scarcity of clinical trials with de-novo immunosuppression has been typical over the last 2 years, several attempts have been made in drug conversion, dosing optimization, and bioequivalence. On the basis of recent clinical and animal studies, future directions of management and treatment are outlined. Recent findings Studies with new tacrolimus formulations showed better bioavailability and lower doses, which might translate into less toxicity. The long-term results of studies with costimulation blockade confirmed their safety and efficacy. Calcineurin inhibitor (CNI)-free regimens based on mTOR inhibitors were shown to be associated with increased risk of the humoral response. Therefore, ongoing trials are predominantly designed to minimize calcineurin inhibitor dose only. Biologics, such as B-cell-specific agents (bortezomib and rituximab) and complement inhibitors (eculizumab) used to treat antibody-mediated rejection, recurrence of glomerulonephritis, are shifted to more preventive applications. The pretransplant quantification of alloreactive memory/effector T cell response may help to better stratify a patient's immunologic risk and allow for drug minimization. Summary Despite clinical trials with innovative protocols with already established agents, tacrolimus-based and induction-based protocols have been shown to be the mainstay of immunosuppressive regimens. In the future, research aims to focus on biomarker-driven immunosuppression and cell therapy approaches.
引用
收藏
页码:387 / 394
页数:8
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