Long term follow-up of the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial

Abstract

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. Demographics are presented with descriptive statistics. Time to event was determined with Kaplan-Meier plots and Mantel-Cox Logrank statistics used to compare groups. 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). 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. 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.