Impact of induction immunosuppression on patient survival in heart transplant recipients treated with tacrolimus and mycophenolic acid in the current allocation era.
Female
Follow-Up Studies
Graft Rejection
/ drug therapy
Graft Survival
Heart Transplantation
/ adverse effects
Humans
Immunosuppression Therapy
/ methods
Immunosuppressive Agents
/ therapeutic use
Male
Middle Aged
Mycophenolic Acid
/ therapeutic use
Postoperative Complications
/ drug therapy
Prognosis
Resource Allocation
Retrospective Studies
Risk Factors
Survival Rate
Tacrolimus
/ therapeutic use
heart transplant
interleukin-2 receptor antagonist
mycophenolic acid
patient survival
rabbit anti-thymocyte globulin
tacrolimus
Journal
Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240
Informations de publication
Date de publication:
08 2019
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.
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
e13651Subventions
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.