Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review.
BACKGROUND
Mycophenolate mofetil (MMF) has increasingly replaced azathioprine (AZA) as the antimetabolite of choice in immunosuppressive protocols. Initial trials comparing MMF with AZA in patients receiving cyclosporine A sandimmune showed a clinical benefit in reducing the incidence of acute rejections. It has been questioned whether this benefit remains significant when using newer formulations of cyclosporine A (neoral) and tacrolimus.


METHODS
Literature searches were performed using the Transplant Library, Cochrane library, Medline, and Embase for all randomized controlled trials directly comparing MMF with AZA in renal transplant recipients. Trials were assessed for quality using the Jadad scoring system. Trials were pooled using meta-analysis software. Confidence intervals were set at 95%.


RESULTS
Nineteen relevant studies were identified, including a total of 3143 patients. MMF significantly reduces the risk of acute rejection when used in combination with any calcineurin inhibitor (relative risk 0.62, 0.55-0.87, P<0.00001). The hazard for graft loss, including death with a functioning graft, is also significantly reduced in patients treated with MMF (hazard ratio 0.76, 0.59-0.98, P=0.037). There is no significant difference in patient survival or renal transplant function between groups. Risk of adverse events, including cytomegalovirus infection, anemia, leukopenia or rates of malignancy, does not differ significantly. A greater risk of diarrhea is seen in MMF-treated patients.


CONCLUSIONS
We have shown that MMF used with a calcineurin inhibitor does indeed confer a clinical benefit over AZA by reducing the risk of acute rejection and also possibly reducing graft loss. This effect is independent of whether MMF is used in combination with sandimmune, neoral or tacrolimus.
Knight
Simon R
SR
Clinical Effectiveness Unit, Centre for Evidence in Transplantation, Royal College of Surgeons of England and the London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
Russell
Neil K
NK
Barcena
Leticia
L
Morris
Peter J
PJ
D000208:Acute Disease; D001379:Azathioprine / Q000627:therapeutic use*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine