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 c o-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreove r ICAM-1 mediates leukocyte invasion from the blood into tissue during infl ammatory processes. In animal studies using mouse monoclonal antibodies aga inst ICAM-1 (enlimomab), renal allograft survival has been improved and rep erfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Trans plant Study (EARTS) was a randomized, double-blind, parallel-group, placebo -controlled study lasting 1 year and performed in 10 transplant centers in Europe. Methods. A total of 262 recipients of cadaveric kidneys were given either e nlimomab or a placebo for 6 days and were given triple immunosuppressive th erapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, a nd each event was assessed by a committee including investigators and indep endent pathologists. Results. There was no significant difference in the incidences of first acu te 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 funct ion (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 occu rred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most im portant non-fatal adverse events were infections; however, there was no sta tistically significant difference between the incidences in the two groups (70% vs. 79%). Conclusion. Short term enlimomab induction therapy after renal transplantat ion did not reduce the rate of acute rejection or DGF.