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

Research output: Contribution to journalArticlepeer-review

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
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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