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Current Status of Immunosuppression
In clinical practice, physicians adjust immuno-suppressive therapy to halance ettectiveness and side-effects. Furl 5 years, cyclosporin A has heen the cornerstone of immunosuppressive therapy across the world, together with steroids and other adjunctive therapy, depending on local protocols. The new advanced formulation, Neural, utters signiticantly hetter and more consistent ahsurption ut cycluspurin A. Over 5,000 patients have heen included in large gluhal clinical studies, and evidence across all organs demonstrates good tulerahility and safety (Table 1).
" Neoral offers significantly better and move consistent absorption of cyclosporin A "
The introduction of Neural presents the potential fur refining and individualising therapy, pussihly leading to a reduction in the cyclosporin A dosage - and even the elimination of concomitant toxic immunosuppressive agents like steroids. Many patients were successfully withdrawn even when using the old formulation, Reviewing retrospective data from the Cullahurative Transplant Study, Prof Gerhard Opelz from Germany demonstrated that in kidney transplant recipients initially assigned to triple therapy, the seven-year graft survival rate was significantly higher in patients switched to steroid-free immunosuppressiun with cycluspurin A, compared to those who remained oil triple or dual therapy with cycluspurin A and steroids (Figure 1). Cf greater relevance, Prof Claudlo Punticelli from Italy reported on a multicentre randumised study of 354 patients comparing the effects of cyclospurin A alone, douhie therapy with steroids, and triple therapy with steroids and azathiuprine. The study showed six-year survival rates of 94 per cent with munutherapy, 88 per cent with douhle therapy and 99 per cent with triple therapy. Ahout halt of the patients could he maintained without steroids using munutherapy with the 010 formulation of cycluspurin A. It seems reasonahie to predict that an even higher proportion of patients can he maintained on steroid-free immunusuppressiun using Neural.
The side-effects associated with the use of cyclospurin A are well understood after more than 15 years of clinical use. The transplant community is now evaluating the side-effect profiles of newer agents where there is less experience in the clinic, In liver transplantation immunosuppressive treatment with FK 506 is associated with a high level of adverse effects. Opelz presented preliminary data from a two-year study of renal transplant recipients showing that, in the first year after transplantation, a much higher rate of lymphuma is seen in the FK 506 group compared to the cycluspurin A group, giving cause fur concern.
Other adverse effects associated with FK 506 include new onset diahetes mellitus; neurupsychutuxicity including headaches, tremor and insomnia; speech pruhiems; nephrutoxicity as well as OP and liver toxicity. Reducing the dose of FK 506 can overcome adverse effects, hut conversion to Neural is a viahie option if this approach tails. Or Sukru Fmre from the USA reported that 18 per cent of 388 liver transplant recipients on munotherapy with EK 506 required conversion to Neural due to uncuntrollahle toxic side-effects. Toxicity prohlems were resolved 0 72 per cent of those patients switched to Neural early fin the first month post transplant) and in 68 per cent of those switched late (after 30 days). There was no increased risk of graft rejection. Immurtosuppressive therapy must he individualised fur each patient, hased on the immunologic risk and on tolerance to specific drugs. The next millennium may witness more flexihility in selecting and using agents.