Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in primary SPK transplantation: 3-year results of the Euro-SPK 001 trial
ek Saudek1
ek1 Adamec11 Institute for Clinical and Experimental Medicine, Diabetes Center, Prague, Czech Republic and 2 Department of Kidney and Pancreas Transplantation and Organ Procurement, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
Correspondence and offprint requests to: Dr Jacques Malaise, Department of Kidney and Pancreas Transplantation and Organ Procurement, Cliniques Universitaires St Luc, Université Catholique de Louvain, Avenue Hippocrate, 10/2207, B-1200 Brussels, Belgium. Email: jacques.malaise{at}chir.ucl.ac.be
Background. Single-centre and retrospective studies suggest superiority of tacrolimus over cyclosporin as cornerstone immunosuppressive therapy for simultaneous pancreas–kidney (SPK) transplantation. This open-label, multicentre trial compared the efficacy and safety of tacrolimus with cyclosporin microemulsion (ME) in diabetic patients with end-stage renal disease undergoing their first cadaveric SPK transplantation. The 3-year results are reported.
Methods. Patients were recruited from 10 centres in Europe and one centre in Israel: 103 were randomized to receive tacrolimus (initial dose: 0.2 mg/kg/day p.o.) and 102 to cyclosporin-ME (7 mg/kg/day p.o.). All patients received concomitant rabbit anti-T-cell globulin induction, mycophenolate mofetil (MMF) and short-term corticosteroids.
Results. Fewer patients receiving tacrolimus (36.9%) than cyclosporin-ME (57.8%) were discontinued from treatment (P = 0.003). The initial episodes of biopsy-proven rejection were moderate or severe in just one out of 31 (3%) tacrolimus-treated patients compared with 11 out of 39 (28%) patients receiving cyclosporin-ME (P = 0.009). While 3-year patient and kidney survival rates were similar in the two treatment groups, pancreas survival was superior with tacrolimus (89.2 vs 72.4%; P = 0.002). Thrombosis resulted in pancreas graft loss in 10 patients receiving cyclosporin-ME and in only two treated with tacrolimus (P = 0.02). Overall adverse event frequency was similar in both groups, but MMF intolerance was more frequent with tacrolimus and hyperlipidaemia more frequent with cyclosporin-ME.
Conclusions. In this 3-year study, tacrolimus was more effective than cyclosporin-ME in preventing moderate or severe kidney or pancreas rejection after SPK transplantation. It also provided superior pancreas survival and reduced the risk of pancreas graft thrombosis.
Keywords: cyclosporin microemulsion; immunosuppression; rejection; simultaneous pancreas–kidney transplantation; tacrolimus