title: 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: Stanford University School of Medicine, Stanford, CA, USA. sbusque@stanford.edu
authors: S
authors: S
authors: Busque
authors: J
authors: J
authors: Leventhal
authors: D C
authors: DC
authors: Brennan
authors: S
authors: S
authors: Steinberg
authors: G
authors: G
authors: Klintmalm
authors: T
authors: T
authors: Shah
authors: S
authors: S
authors: Mulgaonkar
authors: J S
authors: JS
authors: Bromberg
authors: F
authors: F
authors: Vincenti
authors: S
authors: S
authors: Hariharan
authors: D
authors: D
authors: Slakey
authors: V R
authors: VR
authors: Peddi
authors: R A
authors: RA
authors: Fisher
authors: N
authors: N
authors: Lawendy
authors: C
authors: C
authors: Wang
authors: G
authors: G
authors: Chan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001706:Biopsy; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D010880:Piperidines; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases; D009173:Mycophenolic Acid; D016559:Tacrolimus