Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years' results of a randomized prospective clinical trial.
BACKGROUND
With the use of systemic cyclosporin A (CsA), graft prognosis after high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effects. In this prospectively randomized study mycophenolate mofetil (MMF), a safe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty.


METHODS
Twenty-nine high-risk keratoplasty patients were treated with MMF 2x 1 g daily; another 27 patients received CsA, aiming at blood trough levels of 120-150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both groups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively.


RESULTS
During the first year after operation, no graft failure was recorded. Two years postoperatively 92%/82% and 3 years postoperatively 74%/69% of grafts were clear in the MMF and CsA group, respectively (Kaplan Meier P=0.33, logrank test). In total, two graft failures were recorded in the MMF group and four in the CsA group. Three years postoperatively 53% of the grafts were rejection-free in the MMF group and 73% in the CsA group (Kaplan Meier P=0.46, log-rank test). Eight endothelial immune reactions were observed in the MMF group (three under systemic immunosuppression/five thereafter; six mild/two severe) and five in the CsA group (three under systemic immunosuppression/two thereafter; three mild/two severe). Side effects occurred in six patients under MMF and 11 under CsA.


CONCLUSIONS
Concerning efficacy, no statistically significant difference between systemic MMF and systemic CsA administered for 6 months after high-risk penetrating keratoplasty could be shown. Systemic MMF was proven to be at least as safe as CsA. The main mechanism in improving graft survival is a shift from severe to milder endothelial immune reactions, as already demonstrated for CsA. Thus, MMF may become an alternative to CsA for immunosuppression after penetrating high-risk keratoplasty. About 2 years postoperatively, pharmacologically induced relative immunological tolerance slowly decreases. Therefore, long-term administration of systemic MMF should be evaluated in further studies.
Reinhard
T
T
Eye Hospital, Heinrich Heine University, Düsseldorf, Germany. thomasreinhard@uni-duesseldorf.de
Reis
A
A
Böhringer
D
D
Malinowski
M
M
Voiculescu
A
A
Heering
P
P
Godehardt
E
E
Sunmacher
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016572:Cyclosporine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D012449:Safety
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid