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DI-044 Late discontinuation of sotrastaurin: loss in efficacy and safety of renal transplantation?
  1. P Hannun,
  2. C Felipe,
  3. H Tedesco,
  4. J Medina
  1. Universidade Federal de São Paulo, Clinical Research, São Paulo, Brazil

Abstract

Background Renal transplant recipients previously treated by sotrastaurin (STA) had their immunosuppressive regimen changed because the STA development programme was interrupted. It is not established in the literature which immunosuppressive regimen is the most appropriate for late conversion.

Purpose To evaluate the efficacy and safety of changing immunosuppressive treatment in renal transplant recipients previously treated with STA.

Materials and methods A prospective study with 38 renal transplant recipients previously enrolled in clinical trials of the STA development program who were converted to other immunosuppressive regimens. The safety and efficacy data related to conversion were collected 2 weeks before conversion until 12 months after the conversion. Patients on STA and tacrolimus (TAC) were converted to mycophenolate sodium (MPS) and TAC and those who used STA and everolimus (EVL) changed to TAC and everolimus.

Results The mean age was 43 years and mean time of transplant 2.9 ± 1.0 years. A majority were women (53%) and living donor recipients (76%). In 29 (76%) patients, STA was replaced by TAC and in 9 patients (24%) by MPS. Six months after the conversion, the mean creatinine had increased 20% (1.17 vs. 1.40, p < 0. 001) in the population in which TAC was added. This group also experienced reduced renal function compared to baseline (67.5 vs. 56.8 mL/min/1.73 m2, p < 0. 001). The incidence of acute rejection was six times higher in patients using MPS compared to another group of patients (3.5 vs. 22%, p = 0.03), however we did not observe a significant increase in mean creatinine values (1.32 vs. 1.47, p = 0.155) or decrease in renal function (68.1 vs. 61.7 mL/min/1.73 m2 p = 0.089) after conversion. When these same parameters were compared to baseline values for each group there was a significant worsening of creatinine and renal function in the group using TAC and EVL (p < 0.001).

Two patients discontinued the use of everolimus due to lack of efficacy and one due to dyslipidaemia. One patient discontinued the use of tacrolimus due to nephrotoxicity. The MPS dose was reduced in 4 (44%) patients with gastrointestinal adverse events. We observed that after conversion from STA to TAC serum levels of EVL decreased (8.6 vs. 6.0, p < 0. 001), although the same dose of 3 mg/ day was maintained.

Conclusions The late conversion of STA to TAC or MPS reduced the effectiveness and safety of immunosuppressive regimens. The fluctuation of tacrolimus exposure and loss of synergistic effect between the pharmacokinetic of STN and EVL in the first weeks may have been the reason for these results.

No conflict of interest.

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