Evaluation of the effect of tofacitinib exposure on outcomes in kidney transplant patients.

Abstract

Tofacitinib fixed-dose regimens attained better kidney function and comparable efficacy to cyclosporine (CsA) in kidney transplant patients, albeit with increased risks of certain adverse events. This post-hoc analysis evaluated whether a patient subgroup with an acceptable risk-benefit profile could be identified. Tofacitinib exposure was a statistically significant predictor of serious infection rate. One-hundred and eighty six kidney transplant patients were re-categorized to above-median (AME) or below-median (BME) exposure groups. The 6-month biopsy-proven acute rejection rates in AME, BME and CsA groups were 7.8%, 15.7% and 17.7%, respectively. Measured glomerular filtration rate was higher in AME and BME groups versus CsA (61.2 and 67.9 vs. 53.9 mL/min) at Month 12. Fewer patients developed interstitial fibrosis and tubular atrophy (IF/TA) at Month 12 in AME (20.5%) and BME (27.8%) groups versus CsA (48.3%). Serious infections occurred more frequently in the AME group (53.0%) than in BME (28.4%) or CsA (25.5%) groups. Posttransplant lymphoproliferative disorder (PTLD) only occurred in the AME group. In kidney transplant patients, the BME group preserved the clinical advantage of comparable acute rejection rates, improved renal function and a lower incidence of IF/TA versus CsA, and with similar rates of serious infection and no PTLD.

• Authors: F Vincenti, H T Silva, S Busque, P J O'Connell, G Russ, K Budde, A Yoshida, M A Tortorici, M Lamba, N Lawendy, W 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. 15 Issue 6 Pg. 1644-53 (Jun 2015) ISSN: 1600-6143 [Electronic] United States
• PMID: 25649117 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Immunosuppressive Agents
• Piperidines
• Pyrimidines
• Pyrroles
• Cyclosporine
• tofacitinib

Topics

• Adult
• Biopsy
• Cyclosporine (adverse effects, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Glomerular Filtration Rate (drug effects, physiology)
• Graft Rejection (epidemiology, prevention & control)
• Humans
• Immunosuppressive Agents (adverse effects, pharmacology, therapeutic use)
• Kidney (drug effects, pathology, physiopathology)
• Kidney Transplantation
• Lymphoproliferative Disorders (epidemiology)
• Male
• Middle Aged
• Piperidines (adverse effects, pharmacology, therapeutic use)
• Pyrimidines (adverse effects, pharmacology, therapeutic use)
• Pyrroles (adverse effects, pharmacology, therapeutic use)
• Randomized Controlled Trials as Topic
• Risk Assessment
• Risk Factors