Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling

Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling

Bibliographic Details
Main Author: Desai, Vibha CA
Language:English
Published: University of Cincinnati / OhioLINK 2014
Subjects:
Pharmaceuticals
kidney
steroid withdrawal
discrete event simulation
united states renal data system
renal
diabetes
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416579177
id ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1416579177
record_format oai_dc
collection NDLTD
language English
sources NDLTD
topic Pharmaceuticals
kidney
steroid withdrawal
discrete event simulation
united states renal data system
renal
diabetes
spellingShingle Pharmaceuticals
kidney
steroid withdrawal
discrete event simulation
united states renal data system
renal
diabetes
Desai, Vibha CA
Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
author Desai, Vibha CA
author_facet Desai, Vibha CA
author_sort Desai, Vibha CA
title Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
title_short Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
title_full Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
title_fullStr Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
title_full_unstemmed Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling
title_sort comparative effectiveness of tacrolimus-based steroid sparing versus steroid withdrawal regimens in patients with kidney transplantation: results from discrete event simulation modeling
publisher University of Cincinnati / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416579177
work_keys_str_mv AT desaivibhaca comparativeeffectivenessoftacrolimusbasedsteroidsparingversussteroidwithdrawalregimensinpatientswithkidneytransplantationresultsfromdiscreteeventsimulationmodeling
_version_ 1719437514816618496
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14165791772021-08-03T06:28:08Z Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Withdrawal Regimens in Patients with Kidney Transplantation: Results from Discrete Event Simulation Modeling Desai, Vibha CA Pharmaceuticals kidney steroid withdrawal discrete event simulation united states renal data system renal diabetes Background: Acute rejection (AR) and graft loss (GL) that occur as a complication following kidney transplantation (KT) are a major cause of concern in patients with KT. Corticosteroids used as potent immunosuppressants in preventing AR and GL are associated with potentially serious side effects such as development or progression of cardiovascular diseases (CVD), new onset diabetes (NODM), infections and malignancies. Deaths with a functioning graft account for 40% of deaths following KT and CVD are a major cause of these deaths. Trials on tacrolimus-based regimen have found no significant difference in the AR or GL rates and a significant reduction in total cholesterol with steroid withdrawal regimens compared to steroid maintenance regimens. However, majority of these trials were short-term of a duration of <=5 years and included low immunologic risk patients. Long-term effects of these regimens on GL and cardiovascular events such as stroke, myocardial infarction (MI) and deaths due to CVD (D-Cardio) are not known.Objectives: The objectives of the study were to determine the optimal steroid withdrawal strategy that minimizes the incidence of both graft loss as well as cardiovascular events, amongst the five strategies: 1) steroid avoidance 2) 7-day steroid withdrawal 3) 6-month steroid withdrawal 4) 12-month steroid withdrawal and 5) steroid maintenance, using a discrete event simulation model.Methods: A discrete event simulation model was developed that included the following events: AR, GL, MI, stroke, other CVD, NODM, cancer, bacterial infection (BI), cytomegalovirus infection, fracture, D-Cardio, death due to GL and death due to other reasons. The United States Renal Data System registry that follows patients with transplantation was used to derive risk estimates of patients for the above events using parametric regressions adjusting for patients’ demographic characteristics, immunologic risks and comorbidities. The estimates were then used to obtain Weibull distributions to transition a cohort of 10,000 patients in the model, using minimum of sampled time approach. The model was run for 20 years for base patient with mediocre risk frequently seen in practice and for African-American patients and patients with a history of CVD.Results: At the end of 20 years, base patients in the 6-month and 12-month steroid withdrawal group were significantly less likely to experience MI (9.6-9.8% vs 12.2%), NODM (37.2%-42.4% vs 46.4%), BI (51.7%-57.6% vs 67.4%), fractures (51.1%-54.8%% vs 59.1%) and D-Cardio (24.5%-25.7% vs 28.8%), compared to steroid maintenance. The incidence of AR and GL were significantly higher in the steroid avoidance and 12-month steroid withdrawal group compared to the steroid maintenance group (42.6%-51.4% and 57.9%-76.4% vs 30.5% and 40.9%). Compared to base patient, patients with a history of CVD and African-American patients were more likely to have a GL (46.6%-58.0% vs 40.7%-42.2%) and NODM (44.4%-44.9% vs 37.2%-42.4%).Conclusion: At 20 years, the steroid withdrawal between 7-days to 12-month post kidney transplantation has benefits of significantly reduced rates of cardiovascular event with no significantly worse effects on AR and GL rates compared to steroid maintenance in mediocre risk patients. Future simulation studies on a heterogeneous patient population are needed. 2014 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416579177 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416579177 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.

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