title: 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: University of California, San Francisco, CA.
authors: F
authors: F
authors: Vincenti
authors: Hospital do Rim e Hipertensao, São Paulo, Brazil.
authors: H T
authors: HT
authors: Silva
authors: Stanford University, Stanford, CA.
authors: S
authors: S
authors: Busque
authors: Westmead Hospital, Westmead, Australia.
authors: P J
authors: PJ
authors: O'Connell
authors: The Royal Adelaide Hospital, Adelaide, Australia.
authors: G
authors: G
authors: Russ
authors: Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: K
authors: K
authors: Budde
authors: Henry Ford Hospital, Detroit, MI.
authors: A
authors: A
authors: Yoshida
authors: Pfizer Inc, Groton, CT, Collegeville, PA.
authors: M A
authors: MA
authors: Tortorici
authors: Pfizer Inc, Groton, CT, Collegeville, PA.
authors: M
authors: M
authors: Lamba
authors: Pfizer Inc, Groton, CT, Collegeville, PA.
authors: N
authors: N
authors: Lawendy
authors: Pfizer Inc, Groton, CT, Collegeville, PA.
authors: W
authors: W
authors: Wang
authors: Pfizer Inc, Groton, CT, Collegeville, PA.
authors: G
authors: G
authors: Chan
mesh_terms: D000328:Adult; D001706:Biopsy; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D016572:Cyclosporine; C479163:tofacitinib
keywords: clinical research/practice; immunosuppressive regimens; kidney transplantation/nephrology; pharmacokinetics/pharmacodynamics