Sirolimus-Based Therapy With or Without Cyclosporine: Long-Term Follow-up in Renal Transplant Patients J.M. Morales, J.M. Campistol, H. Kreis, G. Mourad, J. Eris, F.P. Schena, J.M. Grinyo, G. Nanni, A. Andres, N. Castaing, Y. Brault, J.T. Burke ABSTRACT 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 improve- ment in renal function with no increased risk of late acute rejection. S INCE ITS INTRODUCTION in the early 1980s, cyclo- sporine (CsA) has been widely used for immunosup- pression in renal transplantation. However, like the other calcineurin inhibitor, tacrolimus, CsA has undesirable adverse effects, including decreased renal function and increased blood pressure, two negative indicators for graft survival. 1,2 Studies comparing sirolimus (SRL) with CsA have found that SRL based therapy results in improved renal function. 3–6 Early CsA withdrawal from a SRL-CsA-corticosteroid regimen has also resulted in low acute rejection rates (22%) with signiﬁcantly better renal function. 7–9 SRL, therefore, represents an alterna- tive to calcineurin inhibitors in the maintenance period after transplantation. We report the results from a long-term, open-label, phase 3b extension study that was conducted to provide additional safety data on renal transplant patients treated with SRL in a variety of regimens. PATIENTS AND METHODS This multicenter, open-label extension study was conducted at approximately 40 centers in Europe, Canada, and Aus- From the Hospital 12 de Octubre (J.M.M.), Madrid, Spain; Hospital Clinic i Provincial (J.M.C.), Barcelona, Spain; Hôpital Necker (H.K.), Paris, France; C.H.U. Lapeyronie (G.M.), Montpel- lier, France; Royal Prince Alfred Hospital (J.E.), Camperdown, Australia; University of Bari (F.P.S.), Bari, Italy; Hospital de Bellvitge (J.M.G.), Barcelona, Spain; Catholic University of the Sacred Heart (G.N.), Rome, Italy; and Wyeth Research (N.C., Y.B., J.T.B.), Paris, France. Supported by a grant from Wyeth Research, Collegeville, Penn, USA. Address reprint requests to Dr José Maria Morales, Hospital 12 de Octubre, Unidad de Transplante Renal, Departamento de Nefrologı´a, Carretera de Andalucia, Km 5.4, 28041 Madrid, Spain. E-mail: jmorales@h12o.es © 2005 by Elsevier Inc. All rights reserved. 0041-1345/05/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2005.01.045 Transplantation Proceedings, 37, 693– 696 (2005) 693