TY - JOUR
T1 - Randomized phase 2b trial of tofacitinib (CP-690,550) in de novo kidney transplant patients
T2 - Efficacy, renal function and safety at 1 year
AU - Vincenti, F.
AU - Tedesco Silva, H.
AU - Busque, S.
AU - O'Connell, P.
AU - Friedewald, J.
AU - Cibrik, D.
AU - Budde, K.
AU - Yoshida, A.
AU - Cohney, S.
AU - Weimar, W.
AU - Kim, Y. S.
AU - Lawendy, N.
AU - Lan, S. P.
AU - Kudlacz, E.
AU - Krishnaswami, S.
AU - Chan, G.
PY - 2012/9
Y1 - 2012/9
N2 - In this Phase 2b study, 331 low-to-moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy-proven acute rejection (BPAR) with a serum creatinine increase of >0.3 mg/dL and >20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6-month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side-effects at the doses evaluated. The authors present the results of a phase 2b trial of tofacitinib in renal transplantation.
AB - In this Phase 2b study, 331 low-to-moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy-proven acute rejection (BPAR) with a serum creatinine increase of >0.3 mg/dL and >20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6-month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side-effects at the doses evaluated. The authors present the results of a phase 2b trial of tofacitinib in renal transplantation.
KW - cyclosporine
KW - kidney
KW - renal function
KW - tofacitinib
UR - http://www.scopus.com/inward/record.url?scp=84865587510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865587510&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2012.04127.x
DO - 10.1111/j.1600-6143.2012.04127.x
M3 - Article
C2 - 22682022
AN - SCOPUS:84865587510
SN - 1600-6135
VL - 12
SP - 2446
EP - 2456
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 9
ER -
