Variation in comedication use according to kidney transplant immunosuppressive regimens: Application of integrated registry and pharmacy claims data

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.