A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group.
BACKGROUND
T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lastingl year and performed in 10 transplant centers in Europe.


METHODS
A total of 262 recipients of cadaveric kidneys were given either enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists.


RESULTS
There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and enlimomab groups (39% vs. 45%), and enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%).


CONCLUSIONS
Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.
Salmela
K
K
4th Department of Surgery, Helsinki University Central Hospital, Finland.
Wramner
L
L
Ekberg
H
H
Hauser
I
I
Bentdal
O
O
Lins
L E
LE
Isoniemi
H
H
Bäckman
L
L
Persson
N
N
Neumayer
H H
HH
Jørgensen
P F
PF
Spieker
C
C
Hendry
B
B
Nicholls
A
A
Kirste
G
G
Hasche
G
G
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002102:Cadaver; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007116:Immunization, Passive; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1