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Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation.

Publication ,  Journal Article
Anderson, DJ; Lo, DJ; Leopardi, F; Song, M; Strobert, EA; Jenkins, JB; Larsen, CP; Kirk, AD
Published in: Clin Transplant
June 2019

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.

Duke Scholars

Published In

Clin Transplant

DOI

EISSN

1399-0012

Publication Date

June 2019

Volume

33

Issue

6

Start / End Page

e13568

Location

Denmark

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Surgery
  • Methotrexate
  • Macaca mulatta
  • Kidney Transplantation
  • Immunosuppressive Agents
  • Immunologic Memory
  • Immunoconjugates
  • Humans
  • Graft Survival
 

Citation

APA
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MLA
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Anderson, D. J., Lo, D. J., Leopardi, F., Song, M., Strobert, E. A., Jenkins, J. B., … Kirk, A. D. (2019). Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation. Clin Transplant, 33(6), e13568. https://doi.org/10.1111/ctr.13568
Anderson, Douglas J., Denise J. Lo, Francis Leopardi, Mingqing Song, Elizabeth A. Strobert, Joe B. Jenkins, Christian P. Larsen, and Allan D. Kirk. “Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation.Clin Transplant 33, no. 6 (June 2019): e13568. https://doi.org/10.1111/ctr.13568.
Anderson DJ, Lo DJ, Leopardi F, Song M, Strobert EA, Jenkins JB, et al. Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation. Clin Transplant. 2019 Jun;33(6):e13568.
Anderson, Douglas J., et al. “Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation.Clin Transplant, vol. 33, no. 6, June 2019, p. e13568. Pubmed, doi:10.1111/ctr.13568.
Anderson DJ, Lo DJ, Leopardi F, Song M, Strobert EA, Jenkins JB, Larsen CP, Kirk AD. Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation. Clin Transplant. 2019 Jun;33(6):e13568.
Journal cover image

Published In

Clin Transplant

DOI

EISSN

1399-0012

Publication Date

June 2019

Volume

33

Issue

6

Start / End Page

e13568

Location

Denmark

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Surgery
  • Methotrexate
  • Macaca mulatta
  • Kidney Transplantation
  • Immunosuppressive Agents
  • Immunologic Memory
  • Immunoconjugates
  • Humans
  • Graft Survival