title: Variation in Comedication Use According to Kidney Transplant Immunosuppressive Regimens: Application of Integrated Registry and Pharmacy Claims Data.
abstract: BACKGROUND
  Modern immunosuppression therapies (ISx) have many side effects, and transplant recipients must take an array of "comedications" to help mitigate complications. Comedication use patterns are not well described in large, representative samples because of lack of data.
  
  
  METHODS
  We integrated national U.S. transplant registry data with pharmacy records (2005-2010) from a large pharmaceutical claims clearinghouse to examine treatments for anemia, metabolic disorders, and infections in relation to ISx regimens in months 6-12 post-transplantation (N = 22,453). Associations of ISx with comedication use (adjusted odds ratio [aOR]) were quantified with multivariate logistic regression including adjustment for recipient, donor, and transplant factors.
  
  
  RESULTS
  Compared to a reference regimen of tacrolimus, mycophenolic acid, and prednisone, sirolimus-based ISx was associated with significantly more common use of erythropoiesis-stimulating agents (aOR 2.52, 95% confidence interval [CI] 2.06-3.09), iron (aOR 2.26, 95% CI 1.92-2.65), statins (aOR 1.47, 95% CI 1.33-1.63), fibrates (aOR 2.35, 95% CI 1.90-2.90), and phosphorous binders (aOR 2.85, 95% CI 1.80-4.50). Patterns were similar after adjustment for first-year estimated glomerular filtration rate, except the association with phosphorous binders was no longer significant. Cyclosporine-based ISx was associated with more common erythropoiesis-stimulating agent use, including after estimated glomerular filtration rate adjustment (aOR 1.61, 95% CI 1.24-2.10). Compared to those who were being administered triple ISx, recipients receiving tacrolimus-based dual and monotherapies had lower use of statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs), and antibacterial agents. Recipients of steroid-free ISx were less commonly treated for post-transplantation diabetes.
  
  
  CONCLUSIONS
  Alternate ISx regimens are associated with varying treatment requirements for hematologic, metabolic. and infectious complications. Comedication use should be considered in the cost-effectiveness and individualization of ISx regimens.
authors.affiliation: Saint Louis University Center for Abdominal Transplantation, St Louis, Missouri. Electronic address: lentinek@slu.edu.
authors.forename: K L
authors.initials: KL
authors.lastname: Lentine
authors.affiliation: University of Michigan, Ann Arbor, Michigan.
authors.forename: A S
authors.initials: AS
authors.lastname: Naik
authors.affiliation: Saint Louis University Center for Abdominal Transplantation, St Louis, Missouri.
authors.forename: M
authors.initials: M
authors.lastname: Schnitzler
authors.affiliation: Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: D
authors.initials: D
authors.lastname: Axelrod
authors.affiliation: Saint Louis University Center for Abdominal Transplantation, St Louis, Missouri.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: D C
authors.initials: DC
authors.lastname: Brennan
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: D L
authors.initials: DL
authors.lastname: Segev
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.
authors.forename: B L
authors.initials: BL
authors.lastname: Kasiske
authors.affiliation: Saint Louis University Center for Abdominal Transplantation, St Louis, Missouri.
authors.forename: H
authors.initials: H
authors.lastname: Randall
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: V R
authors.initials: VR
authors.lastname: Dharnidharka
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000008:administration & dosage; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016247:Information Storage and Retrieval; D016030:Kidney Transplantation / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000008:administration & dosage; D016017:Odds Ratio; D010594:Pharmacies / Q000706:statistics & numerical data*; D011183:Postoperative Complications / Q000188:drug therapy*; D011184:Postoperative Period; D011241:Prednisone / Q000008:administration & dosage; D012042:Registries / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage; D014481:United States
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus