Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in primary SPK transplantation: 3-year results of the Euro-SPK 001 trial.
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.
Saudek
Frantisek
F
Institute for Clinical and Experimental Medicine, Diabetes Center, Prague, Czech Republic.
Malaise
Jacques
J
Boucek
Petr
P
Adamec
Milos
M
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000628:therapy*; D004655:Emulsions; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007557:Israel; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy*; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology; D011446:Prospective Studies; D012449:Safety; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus