Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients

Background 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. Methods We report our experience using monthly tocilizumab (ant...

Full description

Saved in:
Bibliographic Details
Published in:Clinical transplantation 2022-08, Vol.36 (8), p.e14734-n/a
Main Authors: 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
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized
antibody‐mediated rejection
Biopsy
Child
Graft Rejection - drug therapy
Graft Rejection - etiology
Graft Survival
HLA Antigens
Humans
IL‐6
Isoantibodies
kidney
Kidney - pathology
Kidney - physiology
Kidney Transplantation - adverse effects
monoclonal antibody therapy
pediatric
tocilizumab
transplant
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background 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. Methods We report our experience using monthly tocilizumab (anti‐IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From January 2013 to June 2019, a median (IQR) of 12 (6.019.0) 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. Results Median (IQR) time from transplant to AMR was 41.4 (24.367.7) months, and time from AMR to first tocilizumab was 10.6 (8.317.6) months. At median (IQR) follow up of 15.8 (8.435.7) 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 = .015) and C4d scoring (p = .009). The most frequent adverse events were cytopenias. Conclusions 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.
ISSN:0902-0063
1399-0012
DOI:10.1111/ctr.14734