Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.
Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.
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DOI：
10.1111/ctr.14734
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发表时间：
2022-08
影响因子：
2.1
通讯作者：
Puliyanda, Dechu
中科院分区：
文献类型：
--
作者：
Pearl, Meghan;Weng, Patricia L.;Chen, Lucia;Dokras, Aditi;Pizzo, Helen;Garrison, Jonathan;Butler, Carrie;Zhang, Jennifer;Reed, Elaine F.;Kim, Irene K.;Choi, Jua;Haas, Mark;Zhang, Xiaohai;Vo, Ashley;Chambers, Eileen Tsai;Ettenger, Robert;Jordan, Stanley;Puliyanda, Dechu
抗体介导的排斥反应（AMR）的治疗选择有限。最近的研究表明，抑制白细胞介素-6（IL-6）/白细胞介素-6受体（IL-6 R）信号传导可以减轻炎症并减缓AMR进展。我们报告我们的经验，每月托珠单抗（抗IL-6 R）在25例儿童肾移植受者与AMR，难治IVIg/利妥昔单抗。从2013年1月至2019年6月，每例患者接受的托珠单抗中位（IQR）剂量为12（6.0-19.0）剂。对肾功能、活检结果和HLA DSA（通过免疫显性HLA DSA（iDSA）和相对强度评分（RIS））进行系列评估。从移植到AMR的中位（IQR）时间为41.4（24.3-67.7）个月，从AMR到首次使用托珠单抗的时间为10.6（8.3-17.6）个月。在托珠单抗治疗开始后15.8（8.4-35.7）个月的中位（IQR）随访时，除1例同种异体移植物丢失外，肾功能稳定。iDSA或RIS无显著降低。随访活检显示肾小管周围毛细血管炎（p=0.015）和C4d评分（p=0.009）降低。最常见的不良事件是血细胞减少。托珠单抗在难治性AMR儿科患者中耐受性良好，似乎可稳定肾功能。托珠单抗在该人群中治疗AMR的效用应进一步探索。
Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6) /interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression. We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From Jan 2013 to June 2019, a median (IQR) of 12 (6.0–19.0) doses of tocilizumab were given per patient. Serial assessments of renal function, biopsy findings, and HLA DSA (by immunodominant HLA DSA (iDSA) and relative intensity score (RIS)) were performed. Median (IQR) time from transplant to AMR was 41.4 (24.3–67.7) months, and time from AMR to first tocilizumab was 10.6 (8.3–17.6) months. At median (IQR) follow up of 15.8 (8.4–35.7) months post-tocilizumab initiation, renal function was stable except for 1 allograft loss. There was no significant decrease in iDSA or RIS. Follow up biopsies showed reduction in peritubular capillaritis (p=0.015) and C4d scoring (p=0.009). The most frequent adverse events were cytopenias. Tocilizumab in pediatric patients with refractory AMR was well tolerated and appeared to stabilize renal function. The utility of tocilizumab in the treatment of AMR in this population should be further explored.
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