Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation.
Abatacept
/ therapeutic use
Animals
Graft Rejection
/ drug therapy
Graft Survival
/ drug effects
Humans
Immunoconjugates
Immunologic Memory
/ drug effects
Immunosuppressive Agents
/ therapeutic use
Kidney Transplantation
/ adverse effects
Macaca mulatta
Methotrexate
/ therapeutic use
T-Lymphocytes, Regulatory
/ drug effects
costimulation
methotrexate
non-human primate
Journal
Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
05
12
2018
revised:
18
03
2019
accepted:
04
04
2019
pubmed:
22
4
2019
medline:
5
8
2020
entrez:
22
4
2019
Statut:
ppublish
Résumé
Belatacept, the CD28-B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28-B7-specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.
Identifiants
pubmed: 31006146
doi: 10.1111/ctr.13568
pmc: PMC6597274
mid: NIHMS1024837
doi:
Substances chimiques
Immunoconjugates
0
Immunosuppressive Agents
0
Abatacept
7D0YB67S97
Methotrexate
YL5FZ2Y5U1
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
e13568Subventions
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI051731
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI084150
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI079223
Pays : United States
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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