Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study.
BACKGROUND
In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial.


METHODS
The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event.


RESULTS
The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group.


CONCLUSIONS
Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile.
Margreiter
Raimund
R
Department of Transplant Surgery, University Hospital Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. raimund.margreiter@uibk.ac.ch
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014181:Transplantation Immunology / Q000187:drug effects; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D016559:Tacrolimus