Open-Label Study of Planned Transition from Tacrolimus to Sirolimus vs Continued Tacrolimus in Renal Allograft Recipients: Demographics and Interim Safety Results
Hospital do Rim e Hipertensão, São Paulo, Brazil
California Pacific Medical Center, San Francisco, CA
Queen Elizabeth Hospital, Woodville South, Australia
Presbyterian/St Luke's Medical Center, Denver, CO
Pfizer, Collegeville, PA
Meeting: 2013 American Transplant Congress
Abstract number: B1027
Purpose: Evaluate planned transition from tacrolimus (TAC) to sirolimus (SRL) vs continued TAC in renal allograft recipients.
Methods: This open-label, randomized, multinational phase 4 study screened patients at transplant. Patients received TAC and inosine monophosphate dehydrogenase inhibitor from transplant and were randomized 90-150 days posttransplant to continue on TAC or switch to SRL. Patients are being followed for 2y. Interim safety data (treatment-emergent AEs, BCAR, patient survival, graft loss) are presented for all randomized and dosed patients.
Results: In total, 254 patients (SRL 131; TAC 123) were evaluable for safety using preliminary data (mean age, 51.5y; male, 65%; white, 75%). To date, 222 patients (SRL 108; TAC 114) with assessable data have completed 12 mo and 95 patients have completed 24 mo (SRL 44; TAC 51). AEs are summarized in Table. Significantly more patients in the SRL group discontinued due to AEs (25 vs 4; P<.001) and lack of efficacy (6 vs 0; P=.03). Mild T-cell BCAR occurred in significantly more SRL patients (7 vs 0; P=.015), while antibody-mediated rejection was not different between the groups (3 vs 2; P=NS). Three patients in the SRL group and 1 in the TAC group died, and 1 patient in the SRL group experienced impending graft loss.
Conclusions: Interim safety results show no significant differences in patient survival or graft loss between the 2 groups. SRL was associated with a higher incidence of BCAR, AEs, and discontinuations due to AEs, consistent with its known safety profile.
| AE, n (%) | SRL (n=131) | TAC (n=123) |
| Acne | 17 (13.0)* | 0 |
| Anemia | 10 (7.6) | 3 (2.4) |
| Aphthous stomatitis | 12 (9.2)† | 1 (0.8) |
| Diarrhea | 25 (19.1) | 23 (18.7) |
| Dyslipidemia | 14 (10.7)† | 2 (1.6) |
| Headache | 17 (13.0) | 10 (8.1) |
| Hypertension | 14 (10.7) | 9 (7.3) |
| Hyperlipidemia | 11 (8.4)† | 2 (1.6) |
| Leukopenia | 15 (11.5) | 8 (6.5) |
| Mouth ulceration | 15 (11.5)* | 0 |
| Peripheral edema | 30 (22.9)† | 9 (7.3) |
| Proteinuria | 16 (12.2)* | 0 |
| Pyrexia | 16 (12.2) | 7 (5.7) |
| Upper respiratory tract infection | 20 (15.3) | 11 (8.9) |
| Urinary tract infection | 22 (16.8) | 15 (12.2) |
Tedesco-Silva, H.: Grant/Research Support, Novartis, Pfizer, Roche, Veloxis, Bristol-Myers Squibb. Peddi, R.: Grant/Research Support, Novartis, Pfizer, Astellas, Genentech. Russ, G.: Grant/Research Support, Novartis, Pfizer, Speaker’s Bureau, Pfizer, Other, Novartis, Advisory Board, Janssen Cilag, Advisory Board, Pfizer, Advisory Board. Marder, B.: Grant/Research Support, Pfizer. Hahn, C.: Employee, Pfizer, Stockholder, Pfizer. Li, H.: Employee, Pfizer, Stockholder, Pfizer. Flynn, A.: Employee, Pfizer, Stockholder, Pfizer. Schulman, S.: Employee, Pfizer, Stockholder, Pfizer.
To cite this abstract in AMA style:
Tedesco-Silva H, Peddi R, Russ G, Marder B, Hahn C, Li H, Flynn A, Schulman S. Open-Label Study of Planned Transition from Tacrolimus to Sirolimus vs Continued Tacrolimus in Renal Allograft Recipients: Demographics and Interim Safety Results [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/open-label-study-of-planned-transition-from-tacrolimus-to-sirolimus-vs-continued-tacrolimus-in-renal-allograft-recipients-demographics-and-interim-safety-results/. Accessed May 11, 2025.« Back to 2013 American Transplant Congress