NEW IMMUNOSUPPRESSIVE AGENTS

N. Yoshimura¹, K. Uchida², K. Yuzawa³, Y. Fukuda⁴, Y. Ichikawa⁵, K. Akioka⁶, M. Fujisawa⁷, A. Sugitani⁸, S. Ito⁹, T. Nakatani¹⁰, T. Horimi^11
1Organ Transplant,and General Surgery, Kyoto Prefectural University of Medicine, Kyoto/JAPAN, ², Nagoya Daini Red Cross Hospital, Nagoya/JAPAN, ³, Mito Medical Center, Ibaragi/JAPAN, ⁴, JA Hiroshima Hospital, Hiroshima/JAPAN, ⁵, Hyogo Prefectural Nishinomiya Hospital, Hyogo/JAPAN, ⁶, Omihachiman Community Medical Center, Shiga/JAPAN, ⁷, Kobe university, Kobe/JAPAN, ⁸Department Of Organ Transplantation And Regenerative Medicine, Fijita-Heath University, Toyoake Aichi/JAPAN, ⁹, Gifu University, Gifu/JAPAN, ¹⁰Urology, Osaka City Graduate School of Medicine, Osaka/JAPAN, ¹¹, Kochi Health Sciences Center, Kochi/JAPAN

Body: Aims:Mizoribine(Mz),widely used antimetabolite in Japan with less adverse events,inhibits the proliferation of lymphocytes selectively via inhibition of inosine monophosphate dehydrogenase. The aim of this study is to compare the efficacy and safety of high-done Mz with mycophenolate mofetil(MMF) when combined with cyclosporine(CsA), basiliximab(Bas) and corticosteroid in renal transplantation in a Japanese multicenter study. Methods:A total of 90 patients were treated with high-dose Mz (6mg/kg),CsA,Bas and corticosteroid(Mz group). Patients in control group(MMF group:n=72) were treated with MMF(2000mg/day) instead of Mz. In both group,CsA was started at a dose of 7mg/kg to maintain blood levels at the target therapeutic range;200ng/ml(C0),1200ng/ml(C2)and 6000ng-hr/ml (AUC0-9). Bas (20mg/body) was administrated on the day and 4 days after transplantation. Mz was adjusted to maintain target C0 level of 1μg/ml. Rejection was diagnosed by biopsy including episode or protocol. CMVantigenemia (C7-HRP) was measured every two week for 6 mo. Results:All patients and grafts are surviving except for one case who died of infection in Mz group and one case who died of fulminant hepatitis in MMF group.Patients and grafts survival rate was 98.9% in Mz group and 98.6% in MMF group,respectively(n.s.). There was no significant difference in the overall incidence of acute rejection between in Mz group (21.1%) and in MMF group(15.3%).Mean serum creatinine levels at 1 year were 1.51±0.61 mg/dl and 1.54±0.74 mg/dl in Mz and MMF group, respectively(n.s.),demonstrating comparable efficacy. The incidence of CMV disease was 0% and 13.9%(p<0.001) and positive rates of CMV antigenemia were 28.9% and 51.4% in Mz and MMF group,respectively (P<0.01). Gancyclovir-treatment was done in 5.6% of Mz group and in 27.0% of MMF group(p<0.01). There was no significant difference in terms of liver dysfunction or bone marrow suppression.Mean serum unic acid levels were 7.15±1.79mg/dl and 6.03±1.79 mg/dl at 1 mo (p<0.05) and 7.06±1.78mg/dl and 7.15±1.61mg/dl at 3 mo (n.s.) in Mz and MMF group,respectively. Conclusion:High-dose Mz regimen including CsA,Bas, Steroid was effective and safe in renal transplantation reducing the frequency of CMV-related events.

Disclosure: All authors have declared no conflicts of interest.