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

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.

• Authors: 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
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 9 Issue 8 Pg. 1936-45 (Aug 2009) ISSN: 1600-6143 [Electronic] United States
• PMID: 19660021 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Calcineurin Inhibitors
• Immunosuppressive Agents
• Piperidines
• Pyrimidines
• Pyrroles
• tofacitinib
• Janus Kinases
• Mycophenolic Acid
• Tacrolimus

Topics

• Adrenal Cortex Hormones (adverse effects, therapeutic use)
• Adult
• Aged
• Biopsy
• Calcineurin Inhibitors
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Glomerular Filtration Rate (physiology)
• Graft Rejection (immunology, prevention & control)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Janus Kinases (antagonists & inhibitors)
• Kaplan-Meier Estimate
• Kidney (pathology, physiopathology)
• Kidney Transplantation (immunology, pathology, physiology)
• Male
• Middle Aged
• Mycophenolic Acid (adverse effects, analogs & derivatives, therapeutic use)
• Pilot Projects
• Piperidines
• Pyrimidines (adverse effects, therapeutic use)
• Pyrroles (adverse effects, therapeutic use)
• Tacrolimus (adverse effects, therapeutic use)
• Transplantation, Homologous
• Young Adult