TY - JOUR
T1 - Center-driven and clinically driven variation in US liver transplant maintenance immunosuppression therapy
T2 - A national practice patterns analysis
AU - Nazzal, Mustafa
AU - Lentine, Krista L.
AU - Naik, Abhijit S.
AU - Ouseph, Rosemary
AU - Schnitzler, Mark A.
AU - Zhang, Zidong
AU - Randall, Henry
AU - Dharnidharka, Vikas R.
AU - Segev, Dorry L.
AU - Kasiske, Bertram L.
AU - Hess, Gregory P.
AU - Alhamad, Tarek
AU - McAdams-Demarco, Mara
AU - Axelrod, David A.
N1 - Funding Information:
M.N. is supported by the Saint Louis University Liver Center. K.L.L., M.A.S., Z.Z., V.R.D., D.L.S., and D.A.A. are supported by the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Funding Information:
This work was conducted under the auspices of the Minneapolis Medical Research Foundation (MMRF), contractor for the Scientific Registry of Transplant Recipients (SRTR), as a deliverable under contract no. HHSH250201000018C (US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation). As a US Government-sponsored work, there are no restrictions on its use. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the US Government. The authors thank SRTR colleague Nan Booth, MSW, MPH, ELS, for article editing.
Funding Information:
This work was supported by grants from the Saint Louis University Liver Center and the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK102981.
Publisher Copyright:
Copyright © 2018 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
PY - 2018/7
Y1 - 2018/7
N2 - Background. Variation in the use of immunosuppression regimens after liver transplant has not been well described. Methods. Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. Results. In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m 2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). Conclusions. Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.
AB - Background. Variation in the use of immunosuppression regimens after liver transplant has not been well described. Methods. Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. Results. In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m 2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). Conclusions. Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.
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U2 - 10.1097/TXD.0000000000000800
DO - 10.1097/TXD.0000000000000800
M3 - Article
C2 - 30046654
AN - SCOPUS:85064154314
SN - 2373-8731
VL - 4
JO - Transplantation Direct
JF - Transplantation Direct
IS - 7
M1 - e364
ER -