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

Clin Transplant. 2019 Aug;33(8):e13651. doi: 10.1111/ctr.13651. Epub 2019 Jul 19.

Abstract

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.

Keywords: heart transplant; interleukin-2 receptor antagonist; mycophenolic acid; patient survival; rabbit anti-thymocyte globulin; tacrolimus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Follow-Up Studies
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / mortality*
  • Graft Survival
  • Heart Transplantation / adverse effects
  • Heart Transplantation / mortality*
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Postoperative Complications / drug therapy
  • Postoperative Complications / etiology
  • Postoperative Complications / mortality*
  • Prognosis
  • Resource Allocation
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus