Impact of induction immunosuppression on patient survival in heart transplant recipients treated with tacrolimus and mycophenolic acid in the current allocation era.


Journal

Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240

Informations de publication

Date de publication:
08 2019
Historique:
received: 20 11 2018
revised: 01 04 2019
accepted: 16 06 2019
pubmed: 24 6 2019
medline: 12 9 2020
entrez: 24 6 2019
Statut: ppublish

Résumé

The practice of induction therapy with either rabbit anti-thymocyte globulin (r-ATG) or interleukin-2 receptor antagonists (IL-2RA) is common among heart transplant recipients. However, its benefits in the setting of contemporary maintenance immunosuppression with tacrolimus/mycophenolic acid (TAC/MPA) are unknown. We compared post-transplant mortality among three induction therapy strategies (r-ATG vs IL2-RA vs no induction) in a retrospective cohort analysis of heart transplant recipients maintained on TAC/MPA in the Organ Procurement Transplant Network (OPTN) database between the years 2006 and 2015. We used a multivariable model adjusting for clinically important co-morbidities, and a propensity score analysis using the inverse probability weighted (IPW) method in the final analysis. In multivariable IPW analysis, r-ATG (HR = 1.23; 95% CI = 1.05-1.46, P = 0.01) remained significantly associated with a higher mortality. There was a trend toward having a higher mortality in the IL2-RA (HR = 1.11; 95% CI = 1.00-1.24, P = 0.06) group. Subgroup analyses failed to show a patient survival benefit in using either r-ATG or IL2-RA among any of the subgroups analyzed. In this contemporary cohort of heart transplant recipients receiving TAC/MPA, neither r-ATG nor IL2-RA were associated with a survival benefit. On the contrary, adjusted analyses showed a significantly higher mortality in the r-ATG group and a trend toward higher mortality in the IL2-RA group. While caution is needed in interpreting treatment effects in an observational cohort, these data call into question the benefit of induction therapy as a common practice and highlight the need for more studies.

Sections du résumé

BACKGROUND
The practice of induction therapy with either rabbit anti-thymocyte globulin (r-ATG) or interleukin-2 receptor antagonists (IL-2RA) is common among heart transplant recipients. However, its benefits in the setting of contemporary maintenance immunosuppression with tacrolimus/mycophenolic acid (TAC/MPA) are unknown.
METHODS
We compared post-transplant mortality among three induction therapy strategies (r-ATG vs IL2-RA vs no induction) in a retrospective cohort analysis of heart transplant recipients maintained on TAC/MPA in the Organ Procurement Transplant Network (OPTN) database between the years 2006 and 2015. We used a multivariable model adjusting for clinically important co-morbidities, and a propensity score analysis using the inverse probability weighted (IPW) method in the final analysis.
RESULTS
In multivariable IPW analysis, r-ATG (HR = 1.23; 95% CI = 1.05-1.46, P = 0.01) remained significantly associated with a higher mortality. There was a trend toward having a higher mortality in the IL2-RA (HR = 1.11; 95% CI = 1.00-1.24, P = 0.06) group. Subgroup analyses failed to show a patient survival benefit in using either r-ATG or IL2-RA among any of the subgroups analyzed.
CONCLUSION
In this contemporary cohort of heart transplant recipients receiving TAC/MPA, neither r-ATG nor IL2-RA were associated with a survival benefit. On the contrary, adjusted analyses showed a significantly higher mortality in the r-ATG group and a trend toward higher mortality in the IL2-RA group. While caution is needed in interpreting treatment effects in an observational cohort, these data call into question the benefit of induction therapy as a common practice and highlight the need for more studies.

Identifiants

pubmed: 31230375
doi: 10.1111/ctr.13651
doi:

Substances chimiques

Immunosuppressive Agents 0
Mycophenolic Acid HU9DX48N0T
Tacrolimus WM0HAQ4WNM

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13651

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK079328
Pays : United States

Informations de copyright

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Auteurs

Alpesh A Amin (AA)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Faris G Araj (FG)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Venkatesh K Ariyamuthu (VK)

Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas.

Mark H Drazner (MH)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Mehmet U S Ayvaci (MUS)

Information Systems, Naveen Jindal School of Business, University of Texas at Dallas, Dallas, Texas.

Pradeep P A Mammen (PPA)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Mutlu Mete (M)

Department of Computer Science, Texas A&M University-Commerce, Commerce, Texas.

Marcus A Urey (MA)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.

Bekir Tanriover (B)

Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas.

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