Long-Term Effects of Monotherapy with Low Dose Tacrolimus

Purpose Monotherapy with tacrolimus alone (TAC-A) was found to be safe and effective in the TICTAC Trial. However, in that trial, tacrolimus levels were maintained at 10-12 ng/mL over the first year which resulted in a higher serum creatinine level compared to those left in combination. We have been using TAC-A at lower doses in patients who have developed leukopenia or thrombocytopenia due to immunosuppression or a natural state. The presence of cytomegalovirus infections and other viruses excluded those patients from being administered monotherapy. It has not been established whether low dose TAC-A is safe and effective. Methods Between 2010 and 2017 we assessed 151 heart transplant patients who are maintained on monotherapy with TAC-A. Patients were maintained on a low level of TAC-A between 4-7 ng/ml. These patients were assessed for subsequent 1-year rejection, subsequent 3-year survival, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), cardiac allograft vasculopathy (CAV, epicardial disease with angiographic stenosis>30%), and cardiac dysfunction (LVEF ≤ 40%). Furthermore, periodic testing was done with the T-cell immune function test to assess whether these patients were adequately immunosuppressed. Results Patients who were maintained on TAC-A had comparable outcomes compared to patients left in combination immunosuppression (see table). The T-cell immune function test showed that these patients had adequate immunosuppression (average was 276 ng/mL with a range of 56-794 ng/mL and standard deviation of 137.1 ng/mL) with the therapeutic range being 200-550ng/ml. Patients had an average of 11 Tacrolimus lab tests (range: 4-46). Conclusion Low dose TAC-A appears safe and effective in select patients after heart transplantation guided by T cell immune function testing. Further studies with larger number of patients will be needed to confirm these findings.