Everolimus (
Certican) is a novel proliferation signal inhibitor with potent
immunosuppressant effects that has been shown to prevent and reverse acute rejection in preclinical models of kidney, heart, and
lung transplantation. These effects have been confirmed by clinical studies in which
everolimus demonstrated comparable efficacy to
azathioprine and
mycophenolate mofetil in heart and
renal transplantation, respectively, when combined with full-dose
cyclosporine (
CsA; Neoral). Experimental studies have also shown that
everolimus inhibits smooth muscle cell proliferation and prevents neointimal thickening and transplant
arteriosclerosis. Importantly,
everolimus was shown to significantly reduce both the incidence and severity of cardiac allograft vasculopathy in recipients of heart transplants, which if confirmed in long-term studies, could provide a major advantage in these patients. Use of
everolimus was also associated with lower rates of
cytomegalovirus infection in both indications. Studies in which
everolimus was combined with reduced-exposure CsA have demonstrated significantly improved renal function when compared with full-dose regimens, with no loss of efficacy. The results of preclinical and clinical studies with
everolimus thus indicate that this novel proliferation signal inhibitor will be an important addition to the armamentarium by enhancing graft survival and minimizing toxicity.