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Introducing the New Monoclonal Antibodies

State-of-the-art monoclonal antibody therapy, with Simulect (basiliximab) from Novartis and daclizumab from Roche, may address the issue of reducing rejection rates without increased morbidity - a key goal in treating transplantation recipients. In addition to their proven therapeutic benefits, these new treatments are tar more selective than the old monoclonal antibodies, which had significant side-effects.

Further to an international European study puhlished in the Aaocef (1987; 3561183-8) last year, clinical trial evidence presented at the meeting stows that prophylactic use of the new chimeric monoclonal antibody, Simulect in comhination with NeuraL significantly reduces the incidence of acute rejection after transplantation (Figure 1). In addition, Simulect appears to have key advantages over older monoclonals; it can he administered conveniently - in just two doses and is as safe and as well tolerated as placeho.

Transplant recipients are at the highest risk of acute rejection within the first month of surgery. Simulect reduces the incidence of acute rejection by blocking the binding of IL-? to its receptor on activated I-cells. Fharmacokinetic studies have demonstrated that a convenient dosing regimen ot two intravenous infusions of 2Umg ot Simulect given four days apart in the pen-transplant phase are sufficient to block IL-2 receptor binding for the first month after transplantation. Thus, a simple two-dose prophylactic regimen provides patients with protection against acute cellular rejection tor the entire tirst month - a high-risk period. Thus, when used in combination with Neural, Simulect dramatically reduces the risk of acute cellular rejection. In a major randomised US clinical trial presented at the meeting by Pr Roger Rajagopalan of the USA, 346 kidney transplant recipients were given either 2Umg Simulect or placebo at days zero and four post-transplant in addition to conventional immunosuppression with Neoral and steroids.

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The incidence of biopsy-confirmed rejection episodes within six months ot surgery were just 33 per cent in the group given monoclonal antibody treatment compared with 46 per cent in the placebo group (p=U.U1 5). Furthermore, there was less use ot steroids in the early weeks post-transplant and less need for anti- lymphocyte antibody anti-rejection therapy among patients who received Simulect (18 per cent) compared with those who received placebo (28 per cent) (p=O.041). Sixty seven per cent of the Simulect group was rejection-free at six months post-transplant compared with 54% of the placebo group (Figure 2). There was no ditference in the incidence ot adverse effects between the placebo and treatment groups up to 12 months post-transplant.

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" When used in combination with Neoral, Simulect dramatically reduces the risk of acute cellular rejection "

Preliminary findings from an economic evaluation of the Phase Ill international European trial on the prophylactic use of Simulect in addition to immunosuppressive therapy with Neoral and corticosteroids, shows that only 15 per cent of Simulect patients have an acute rejection episode before day 25 compared with 42 per cent ot patients who receive standard immunosuppressive therapy alone.

Thus, Simulect could potentially be used to promote earlier discharge of transplant patients from hospital with subsequent cost savings for the hospital and improved quality of life for patients. Further studies are ongoing in liver and heart transplantation and it is expected that these studies will involve more than 2,UUU patients. It is hoped that key studies in renal patients will show that Simulect's beneficial clinical effects on acute rejection translate into protection from chronic rejection and into subsequent long-term cost savings.