Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.
IL-6
antibody-mediated rejection
kidney
monoclonal antibody therapy
pediatric
tocilizumab
transplant
Journal
Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
18
05
2022
received:
27
02
2022
accepted:
20
05
2022
pubmed:
4
6
2022
medline:
11
8
2022
entrez:
3
6
2022
Statut:
ppublish
Résumé
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 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35657013
doi: 10.1111/ctr.14734
pmc: PMC9378624
mid: NIHMS1811181
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
HLA Antigens
0
Isoantibodies
0
tocilizumab
I031V2H011
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14734Subventions
Organisme : NIAID NIH HHS
ID : K23 AI139335
Pays : United States
Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Am J Transplant. 2007 Feb;7(2):408-15
pubmed: 17229080
Am J Transplant. 2018 Feb;18(2):293-307
pubmed: 29243394
Am J Transplant. 2009 May;9(5):1063-71
pubmed: 19344434
Nat Rev Nephrol. 2012 Apr 17;8(6):348-57
pubmed: 22508180
Kidney Int. 2017 Mar;91(3):729-737
pubmed: 28104301
Pediatr Transplant. 2017 Dec;21(8):
pubmed: 28929636
Pediatr Nephrol. 2016 Aug;31(8):1341-8
pubmed: 27048228
Trials. 2019 Jan 11;20(1):37
pubmed: 30635033
Transpl Int. 2019 Jan;32(1):38-48
pubmed: 30076765
Clin Transplant. 2020 Aug;34(8):e13908
pubmed: 32415711
Rheumatology (Oxford). 2022 Mar 2;61(3):953-962
pubmed: 33993216
Transplantation. 2009 Aug 27;88(4):568-74
pubmed: 19696641
Transplant Proc. 2009 Jan-Feb;41(1):429-30
pubmed: 19249572
Exp Clin Transplant. 2013 Oct;11(5):404-7
pubmed: 24128133
J Am Soc Nephrol. 2009 Mar;20(3):629-37
pubmed: 19158356
J Am Soc Nephrol. 2012 Dec;23(12):2061-71
pubmed: 23160511
Rheumatol Int. 2021 Jul 9;:
pubmed: 34241658
J Am Soc Nephrol. 2013 Mar;24(4):655-64
pubmed: 23449533
Am J Transplant. 2009 Nov;9(11):2520-31
pubmed: 19843030
Transplantation. 2008 Nov 15;86(9):1214-21
pubmed: 19005402
Am J Transplant. 2012 Feb;12(2):388-99
pubmed: 22081892
Transplantation. 2020 Apr;104(4):856-863
pubmed: 31385933
Transplantation. 2017 Jan;101(1):32-44
pubmed: 27547870
Clin Exp Immunol. 1988 Feb;71(2):314-9
pubmed: 3280187
Nephrol Dial Transplant. 1997 Apr;12(4):753-9
pubmed: 9141007
Pediatr Transplant. 2013 Nov;17(7):E149-55
pubmed: 23901848
Transplantation. 2010 Jul 15;90(1):68-74
pubmed: 20463643
Am J Transplant. 2009 Nov;9(11):2532-41
pubmed: 19843031
Am J Transplant. 2017 Sep;17(9):2381-2389
pubmed: 28199785
Front Pharmacol. 2021 Apr 15;12:651222
pubmed: 33935762
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Hum Immunol. 2016 Apr;77(4):346-52
pubmed: 26867813
J Am Soc Nephrol. 2021 Mar;32(3):708-722
pubmed: 33443079
Am J Transplant. 2015 Nov;15(11):2921-30
pubmed: 26096305
Transplantation. 2021 Aug 1;105(8):1818-1824
pubmed: 33534530
Am J Transplant. 2021 Jul;21(7):2543-2554
pubmed: 33331082
N Engl J Med. 2005 Feb 10;352(6):558-69
pubmed: 15703421
Am J Kidney Dis. 2021 Apr;77(4 Suppl 1):A7-A8
pubmed: 33752804
Transpl Int. 2019 Aug;32(8):775-788
pubmed: 30955215
Transplantation. 2020 May;104(5):911-922
pubmed: 31895348
Pediatr Transplant. 2019 Dec;23(8):e13597
pubmed: 31657095
Pediatr Transplant. 2017 May;21(3):
pubmed: 28092129
J Am Soc Nephrol. 2018 Feb;29(2):591-605
pubmed: 29242250
Am J Transplant. 2014 Feb;14(2):272-83
pubmed: 24472190
Transpl Int. 2012 Nov;25(11):1165-73
pubmed: 22897111