Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.
BACKGROUND
Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection. However, evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid. We aimed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin.


METHODS
The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion (Neoral) and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. Analysis was by intention to treat.


RESULTS
168 patients per group entered phase A. 56 (34%) assigned mycophenolate mofetil and 58 (35%) assigned azathioprine had clinical rejections (risk reduction [RR] on mycophenolate mofetil compared with azathioprine 13.7% [95% CI -25.7% to 40.7%], p=0.44). 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 (16%) taking mycophenolate mofetil and 11 (12%) taking azathioprine had clinical rejections (RR -16.2%, [-157.5% to 47.5%], p=0.71). Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine (phase A 2665 Euros [SD 586] vs Euros 184 [62]; phase B 5095 Euros [2658] vs 322 Euros [170], p<0.0001 for both).


CONCLUSIONS
In recipients of cadaver kidney-transplants given ciclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive. Standard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil, at least for kidney grafts.
Clinical Research Centre for Rare Diseases, Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Bergamo, Italy.
Giuseppe
G
Remuzzi
Mariadomenica
M
Lesti
Eliana
E
Gotti
Maria
M
Ganeva
Borislav D
BD
Dimitrov
Bogdan
B
Ene-Iordache
Giulia
G
Gherardi
Donato
D
Donati
Maurizio
M
Salvadori
Silvio
S
Sandrini
Umberto
U
Valente
Giuseppe
G
Segoloni
Georges
G
Mourad
Stefano
S
Federico
Paolo
P
Rigotti
Vito
V
Sparacino
Jean-Louis
JL
Bosmans
Norberto
N
Perico
Piero
P
Ruggenenti
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine