Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: A pilot study in de novo kidney allograft recipients

S. Busque*, J. Leventhal, D. C. Brennan, S. Steinberg, G. Klintmalm, T. Shah, S. Mulgaonkar, J. S. Bromberg, F. Vincenti, S. Hariharan, D. Slakey, V. R. Peddi, R. A. Fisher, N. Lawendy, C. Wang, G. Chan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

This randomized, pilot study compared the Janus kinase inhibitor CP-690,550 (15 mg BID [CP15] and 30 mg BID [CP30], n = 20 each) with tacrolimus (n = 21) in de novo kidney allograft recipients. Patients received an IL-2 receptor antagonist, concomitant mycophenolate mofetil (MMF) and corticosteroids. CP-690,550 doses were reduced after 6 months. Due to a high incidence of BK virus nephropathy (BKN) in CP30, MMF was discontinued in this group. The 6-month biopsy-proven acute rejection rates were 1 of 20, 4 of 20 and 1 of 21 for CP15, CP30 and tacrolimus groups, respectively. BKN developed in 4 of 20 patients in CP30 group. The 6-month rates of cytomegalovirus disease were 2 of 20, 4 of 20 and none of 21 for CP15, CP30 and tacrolimus groups, respectively. Estimated glomerular filtration rate was >70 mL/min at 6 and 12 months (all groups). NK cells were reduced by ≤77% in CP-690,550-treated patients. In the CP-690,550 arms, there were modest lipid elevations and a trend toward more frequent anemia and neutropenia during the first 6 months. These data suggest that coadministration of CP-690,550 30 mg BID with MMF is associated with overimmunosuppression. At 15 mg BID, the efficacy/safety profile was comparable to the tacrolimus control group, excepting a higher rate of viral infection. Further dose-ranging evaluation of CP-690,550 is warranted.

Original languageEnglish (US)
Pages (from-to)1936-1945
Number of pages10
JournalAmerican Journal of Transplantation
Volume9
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • CP-690,550
  • Immunosuppression
  • Inhibitor
  • Janus kinase (JAK)
  • Kidney
  • Transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: A pilot study in de novo kidney allograft recipients'. Together they form a unique fingerprint.

Cite this