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

Douglas J. Anderson, Denise J. Lo, Francis Leopardi, Mingqing Song, Elizabeth A. Strobert, Joe B. Jenkins, Christian P. Larsen, Allan D. Kirk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Article numbere13568
JournalClinical Transplantation
Issue number6
StatePublished - Jun 2019
Externally publishedYes


  • costimulation
  • methotrexate
  • non-human primate


Dive into the research topics of 'Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation'. Together they form a unique fingerprint.

Cite this