Background
Tacrolimus (TAC) monotherapy has been compared to TAC and mycophenolate mofetil (MMF)
in the randomized Tacrolimus in Combination, Tacrolimus Alone Compared (TICTAC) trial.
Long term results are now reported.
Methods
Demographics are presented with descriptive statistics. Time to event was determined
with Kaplan-Meier plots and Mantel-Cox Logrank statistics used to compare groups.
Results
One hundred and forty-seven (98 %) of the initial 150 TICTAC trial patients had long-term
follow-up data available. The median follow-up was 13.4 years (interquartile range
7.2-15.1 years). Post-transplant survival at 5, 10 and 15 years in the TAC monotherapy
group was 84.5 %, 66.9 %, and 52.7 %, and 94.4 %, 78.2 % and 56.1 % for patients randomized
to TAC / MMF (p = 0.19 logrank). The freedom from cardiac allograft vasculopathy (≥grade 1) was 100
%, 87.5 %, 69.3 % and 46.5 % at 1, 5, 10 and 15 years in the monotherapy group and
100 %, 76.9 %, 68.1 % and 54.4 % in the TAC/MMF group respectively (p = 0.96 logrank). Crossover of treatment assignment did not alter these findings.
The freedom from dialysis or renal replacement was 92.8 %, 84.2 % and 68.4 % for TAC
monotherapy patients versus 100 %, 93.4 % and 82.3 % for TAC/MMF patients at 5, 10
and 15-years post-transplant (p = 0.15 logrank).
Conclusions
Patients randomized to TAC/ MMF with 8-week steroid weaning had comparable outcomes
to those with similar steroid regimen but discontinuation of MMF at 2 week post-transplant.
The best outcomes were noted for patients initiated on TAC/ MMF including those where
MMF was discontinued for intolerance. Both strategies are reasonable alternatives
for patients post heart transplant.
Condensed Abstract
Tacrolimus monotherapy was compared to TAC and mycophenolate mofetil without long
term steroids in the randomized Tacrolimus in Combination, Tacrolimus Alone Compared
(TICTAC) trial. Post-transplant survival at 5, 10 and 15 years in the TAC monotherapy
group was 84.5%, 66.9 %, and 52.7 %, and 94.4 %, 78.2 % and 56.1 % for patients randomized
to TAC / MMF (p = 0.19 logrank). Cardiac allograft vasculopathy and kidney failure were similar between
groups. Immunosuppression should be individualized to avoid over treating some patients
while undertreating others.
KEYWORDS
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- New directions in immunosuppression after heart transplantation.Nat Rev Cardiol. 2013; 10: 422-427
- Tacrolimus and cardiac transplantation: a comparison of monotherapy and steroid-dependent patients.Transplant Proc. 2002; 34: 1845-1846
- Tacrolimus monotherapy in adult cardiac transplant recipients: intermediate-term results.J Heart Lung Transplant. 2001; 20: 59-70
- Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial).J Heart Lung Transplant. 2007; 26: 992-997
- A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.Circ Heart Fail. 2011; 4: 129-137
- International society for heart and lung transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.J Heart Lung Transplant. 2010; 29: 717-727
- The international thoracic organ transplant registry of the international society for heart and lung transplantation: thirty-eighth adult heart transplantation report - 2021; focus on recipient characteristics.J Heart Lung Transplant. 2021; 40: 1060-1072
- Duration of corticosteroid use and long-term outcomes after adult heart transplantation: a contemporary analysis of the international society for heart and lung transplantation registry.Clin Transplant. 2018; 32: e13340
- Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients.Am J Transplant. 2005; 5: 720-728
- Association between chronic use of immunosuppresive drugs and clinical outcomes from Coronavirus Disease 2019 (COVID-19) hospitalization: a retrospective cohort study in a large US health system.Clin Infect Dis. 2021; 3: e4124-e4130
- SARS-CoV2 and immunosuppression: a double-edged sword.Transpl Infect Dis. 2020; 22: e13404
- Characteristics and outcomes of recipients of heart transplant with Coronavirus Disease 2019.JAMA Cardiol. 2020; 5: 1165-1169
- Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center.Nephrol Dial Transplant. 2020; 35: 1250-1261
- Kidney transplant recipients infected by COVID-19: review of the initial published experience.Transpl Infect Dis. 2020; 22: e13426
- Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: Possible improvement by mycophenolate mofetil reduction.Clin Transplant. 2022; 36e14790
- Comparison of the immune response after an extended primary series of COVID-19 vaccination in kidney transplant recipients receiving standard versus mycophenolic acid-sparing immunosuppressive regimen.Transplant Direct. 2022; 8: e1393
- Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.JCI Insight. 2022; 7e157836
- Ongoing mycophenolate treatment impairs Anti-SARS-CoV-2 vaccination response in patients affected by chronic inflammatory autoimmune diseases or liver transplantation recipients: results of the RIVALSA prospective cohort.Viruses. 2022; 14: 1766
- High-dose mycophenolate use at vaccination is independently associated with breakthrough COVID-19 among lung transplant patients.Transplantation. 2022; 106: e271-e274
- Predicting a positive antibody response after 2 SARS-CoV-2 mRNA vaccines in transplant recipients: a machine learning approach with external validation.Transplantation. 2022; 106: e452-e460
- mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients.Am J Transplant. 2022; 22: 3137-3142
- The international thoracic organ transplant registry of the international society for heart and lung transplantation: 37th adult heart transplantation report-2020; focus on deceased donor characteristics.J Heart Lung Transplant. 2020; 39: 1003-1015
- Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940
Article info
Publication history
Published online: February 07, 2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 International Society for Heart and Lung Transplantation. All rights reserved.
