Browsing by Author "Chen, Jeanne"

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    Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program
    (Wiley, 2023) Tillman, Emma; Nikirk, Miley G.; Chen, Jeanne; Skaar, Todd C.; Shugg, Tyler; Maddatu, Judith P.; Sharfuddin, Asif A.; Eadon, Michael T.; Medicine, School of Medicine
    Tacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence-based guidelines for CYP3A5 normal/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive CYP3A genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for CYP3A5 and CYP3A4 was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic-recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third-party payers. CYP3A5 normal/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only ≈66% of African Americans in our cohort were normal/intermediate metabolizers who required higher doses. Routine CYP3A5 genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.
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    Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience
    (Elsevier, 2021-12) Adebiyi, Oluwafisayo; Umukoro, Peter; Sharfuddin, Asif; Taber, Tim; Chen, Jeanne; Lane, Kathleen A.; Li, Xiaochun; Goggins, Williams; Yaqub, Muhammad S.; Biostatistics, School of Public Health
    Background Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. Methods We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. Results No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). Conclusions In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.
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    Steroid Free Three Drug Maintenance Regimen for Pancreas Transplant Alone: Comparison of Induction with Rabbit Antithymocyte Globulin +/- Rituximab
    (Wiley, 2018) Fridell, Jonathan; Mangus, Richard; Chen, Jeanne; Taber, Tim; Cabrales, Arianna E.; Sharfuddin, Asif; Yaqub, Muhammad; Powelson, John; Surgery, School of Medicine
    Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three‐drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7‐ and 90‐ days were 4% and 5%, and one year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7 or 90 day graft loss, 1 year patient or graft survival or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three drug immunosuppression regimen is an excellent strategy for PTA recipients.