Sirolimus-Based Therapy With or Without Cyclosporine: Long-Term Follow-up in Renal Transplant Patients

• Published in: Transplantation proceedings Vol. 37; no. 2; pp. 693 - 696
• Main Authors: Morales, J.M., Campistol, J.M., Kreis, H., Mourad, G., Eris, J., Schena, F.P., Grinyo, J.M., Nanni, G., Andres, A., Castaing, N., Brault, Y., Burke, J.T.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2005; Elsevier Science
• Subjects: Adult; Biological and medical sciences; Creatinine - blood; Cyclosporine - therapeutic use; Drug Therapy, Combination; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glomerular Filtration Rate; Graft Rejection - epidemiology; Histocompatibility Testing; Humans; Immunosuppressive Agents - therapeutic use; Kidney Transplantation - immunology; Kidney Transplantation - mortality; Kidney Transplantation - physiology; Male; Medical sciences; Sirolimus - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Survival Analysis; Time Factors; Tissue Donors; Tissue, organ and graft immunology; Human; Sirolimus; Lactone; Patient; Transplantation; Homotransplantation; Macrolide; Long term; Kidney; Macrocycle; Medicine; Antibiotic; Treatment; Urinary system; Follow up study; Surgery; Graft; Ciclosporin; Immunosuppressive agent; Antibacterial agent
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2005.01.045

This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group,
n = 98) or without CsA (SRL group,
n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for ≥3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%,
P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.