BTS 2013 Report – The TAESR trial – outcomes after one year

by Maria Dalby reporting on the presentation by Adam McLean, Hammersmith Hospital, London.  Tacrolimus administered once daily in an extended-release formulation is as safe and effective as conventional twice-daily tacrolimus after alemtuzumab induction and early steroid withdrawal. No difference was seen between the two treatment arms in patient or graft survival or rejection rates, and stable tacrolimus plasma levels were established equally quickly in both groups.

Dr Adam McLean at the West London Renal & Transplant Centre at Hammersmith Hospital is the principal investigator of the Standard Versus Prolonged-release Tacrolimus Monotherapy After Alemtuzumab Induction in Kidney Transplantation (TAESR), and reported on the outcomes after one year.

Tacrolimus administered twice daily has been included in the standard immunosuppressive protocol at Hammersmith Hospital since 1995. The rationale for the TAESR trial was to validate the safety and efficacy of once-daily extended-release tacrolimus as a maximally simplified regimen versus the standard protocol. Patients were randomised 1:1 to receive either extended-release (once daily) or conventional (twice daily) tacrolimus as maintenance monotherapy following induction therapy with alemtuzumab and a short course (7 days) of corticosteroids. Patients who had received prior significant myelosuppressive immunosuppression were excluded from the trial, as were patients who were hepatitic B or C or HIV positive or had undergone simultaneous pancreas and kidney transplantation or antibody-incompatible transplantation. With regard to procedures, the standard protocol was followed which involves aggressive monitoring for rejection with biopsies and treatment of rejection episodes with intravenous and oral steroids and mycophenolate mofetil. The primary efficacy outcome was patient survival with a functioning graft at one year. Based on previous experience, the study was statistically powered to detect a non-inferiority margin of 10% between once-daily and twice-daily tacrolimus.

A total of 52 patients received once-daily tacrolimus and 50 patients received twice-daily tacrolimus. The one-year primary efficacy endpoint was achieved in November 2012. No statistically significant difference was observed between the two treatment groups with respect to survival with a functioning graft (92.3% in the once-daily tacrolimus arm vs. 96% in the twice-daily tacrolimus arm, p=NS). In addition, there was no statistically significant difference in the rate of delayed graft function (23.1% vs. 22.0%; p=0.584) or the time to achieve stable tacrolimus plasma levels (7.7±1.4 days vs. 9.4±1.7 days; 95% CI 0.54, 1.24; p=0.344). One death occurred in the twice-daily tacrolimus group due to liver necrosis; two patients in the once-daily arm experienced graft failure due to haemorrhage and one due to antibody-mediated rejection (AMR), whereas one patient in the twice-daily arm experienced graft failure due to an infection. Rejection-free survival at one year was 14% in the once-daily arm compared with 16% in the twice-daily arm (p=NS). No statistically significant difference was seen with respect to graft function (measured as creatinine clearance and estimated glomerular filtration rate) or tacrolimus trough levels. Summarising, Dr McLean pointed out that despite the somewhat weak power of the study, the results at one year show that once-daily tacrolimus is as safe and effective as the twice daily option, with the potential for greater patient convenience and reduced nephrotoxicity.