title: Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Maintenance Regimens in Kidney Transplantation: Results from Discrete Event Simulation.
abstract: Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk.
  
  
  
  To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal.
  
  
  
  A discrete event simulation was developed including, as events, AR, GL, myocardial infarction (MI), stroke, cytomegalovirus, and new onset diabetes mellitus (NODM), among others. Data from the United States Renal Data System were used to estimate event-specific parametric regressions, which accounted for steroid-sparing regimen (avoidance, early 7-d withdrawal, 6-mo withdrawal, 12-mo withdrawal, and maintenance) as well as patients' demographics, immunologic risks, and comorbidities. Regression-equation results were used to derive individual time-to-event Weibull distributions, used, in turn, to simulate the course of patients over 20 y.
  
  
  
  Patients on steroid avoidance or an early-withdrawal regimen were more likely to experience AR (45.9% to 55.0% v. 33.6%, P < 0.05) and GL (51.5% to 68.8% v. 37.8%, P < 0.05) compared to patients on steroid maintenance. Patients in 6-mo and 12-mo steroid withdrawal groups were less likely to experience MI (11.1% v. 13.3%, P < 0.05), NODM (30.7% to 34.4% v. 37.7%, P < 0.05), and cardiac death (29.9% to 30.5% v. 32.4%, P < 0.05), compared to steroid maintenance.
  
  
  
  Strategies of 6- and 12-mo steroid withdrawal post-kidney transplantation are expected to reduce the rates of adverse cardiovascular events and other outcomes with no worsening of AR or GL rates compared with steroid maintenance.
authors.affiliation: Researcher, HealthCore, Andover, MA, USA (VCAD).
authors.forename: Vibha C A
authors.initials: VCA
authors.lastname: Desai
authors.affiliation: Assistant Professor of Operations Management, College of Business, Clemson University, Clemson, SC, USA (YF).
authors.forename: Yann
authors.initials: Y
authors.lastname: Ferrand
authors.affiliation: Assistant Professor of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USA (TMC).
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Cavanaugh
authors.affiliation: Professor of Economics, Carl H. Lindner College of Business, and Adjunct Professor of Clinical Pharmacy, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USA (CMLK).
authors.forename: Christina M L
authors.initials: CML
authors.lastname: Kelton
authors.affiliation: Chief Scientist, Evidera, and Adjunct Professor of Epidemiology and of Medicine, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada (JJC).
authors.forename: J Jaime
authors.initials: JJ
authors.lastname: Caro
authors.affiliation: Professor of Pediatrics-Nephrology, School of Medicine, University of Colorado, Aurora, CO, USA (JG).
authors.forename: Jens
authors.initials: J
authors.lastname: Goebel
authors.affiliation: Chair and Professor of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USA (PCH).
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Heaton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology; D003198:Computer Simulation; D016208:Databases, Factual; D020000:Decision Support Systems, Clinical; D005260:Female; D006084:Graft Rejection / Q000150:complications*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013256:Steroids / Q000494:pharmacology*; D016559:Tacrolimus / Q000494:pharmacology*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D016559:Tacrolimus
keywords: acute rejection; cardiovascular event; discrete event simulation; graft loss; immunosuppression; kidney transplant; steroid maintenance; steroid withdrawal