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托珠单抗治疗肾移植受者急性活动性抗体介导排斥反应的疗效与安全性

Efficacy and Safety of Tocilizumab in the Treatment of Acute Active Antibody-mediated Rejection in Kidney Transplant Recipients.

作者信息

Pottebaum April A, Venkatachalam Karthikeyan, Liu Chang, Brennan Daniel C, Murad Haris, Malone Andrew F, Alhamad Tarek

机构信息

Department of Pharmacy, Barnes Jewish Hospital, St. Louis, MO.

Division of Nephrology, Washington University in St. Louis, St. Louis, MO.

出版信息

Transplant Direct. 2020 Mar 13;6(4):e543. doi: 10.1097/TXD.0000000000000988. eCollection 2020 Apr.

Abstract

UNLABELLED

Antibody-mediated rejection (AMR) continues to have a deleterious impact on kidney allograft survival. Recent evidence supports use of tocilizumab for treatment of chronic active AMR, but it has not been assessed for treatment of acute active AMR.

METHODS

We performed a single-center, observational study of kidney transplant recipients who received at least 1 dose of tocilizumab in addition to conventional therapies for acute active AMR between October 2016 and October 2018 with follow-up through August 2019.

RESULTS

Seven patients were included. All 7 patients received tocilizumab 8 mg/kg (max dose, 800 mg) monthly. We noted a 50% or greater reduction in immunodominant donor-specific antibodies in 4 of 6 patients. Renal function improved or stabilized in all patients throughout the duration of therapy. One patient developed cytomegalovirus esophagitis and 1 had a potential hypersensitivity reaction. In the extended follow-up, 1 patient had mixed rejection and 2 patients had T-cell-mediated rejection, which occurred 6 to 24 mo after completion of therapy.

CONCLUSIONS

Tocilizumab may be considered as an addition to conventional therapies for treatment of acute active AMR. More studies are needed to determine which patients may benefit from therapy and to examine the appropriate duration of treatment.

摘要

未标注

抗体介导的排斥反应(AMR)持续对肾移植受者的存活产生有害影响。近期证据支持使用托珠单抗治疗慢性活动性AMR,但尚未对其治疗急性活动性AMR进行评估。

方法

我们对2016年10月至2018年10月期间接受急性活动性AMR常规治疗的同时至少接受1剂托珠单抗治疗的肾移植受者进行了一项单中心观察性研究,并随访至2019年8月。

结果

纳入7例患者。所有7例患者均每月接受8mg/kg(最大剂量800mg)的托珠单抗治疗。我们注意到6例患者中有4例免疫优势供体特异性抗体减少了50%或更多。在整个治疗期间,所有患者的肾功能均有所改善或稳定。1例患者发生巨细胞病毒食管炎,1例有潜在的过敏反应。在延长随访中,1例患者发生混合性排斥反应,2例患者发生T细胞介导的排斥反应,均在治疗完成后6至24个月出现。

结论

托珠单抗可作为急性活动性AMR常规治疗的辅助药物。需要更多研究来确定哪些患者可能从治疗中获益,并探讨合适的治疗时长。

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