Everolimus with Optimized Cyclosporine Dosing in Renal Transplant Recipients: 6-Month Safety and Efficacy Results of Two Randomized Studies

American Journal of Transplantation

Volumn 4, Issue 4, 2004, Pages 626-635

  Vitko, Stefan ^a   Tedesco, Helio ^b   Eris, Josette ^c   Pascual, Julio ^d   Whelchel, John ^e   Magee, John C ^f   Campbell, Scott ^g   Civati, Giovanni ^h   Bourbigot, Bernard ⁱ   Alves Filho, Gentil ^j   Leone, John ^k   Garcia, Valter Duro ^l   Rigotti, Paolo ^m   Esmeraldo, Ronaldo ⁿ   Cambi, Vincenzo ^o   Haas, Tomas ^p   Jappe, Annette ^p   Bernhardt, Peter ^p   Geissler, Johanna ^p   Cretin, Nathalie ^p  

^a INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE   (Czech Republic)

^b HOSPITAL DO RIM E HIPERTENSÃO   (Brazil)

^c ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^d HOSPITAL RAMÓN Y CAJAL   (Spain)

^e PIEDMONT HOSPITAL   (United States)

^f UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^g PRINCESS ALEXANDRA HOSPITAL   (Australia)

^h OSPEDALE NIGUARDA CA GRANDA   (Italy)

ⁱ BREST UNIVERSITY HOSPITAL   (France)

^j UNIVERSITY OF CAMPINAS   (Brazil)

^k TAMPA GENERAL HOSPITAL   (United States)

^l Santa Casa de Misericoridia   (Brazil)

^m Policlinico Hospital   (Italy)

ⁿ HOSPITAL GERAL DE FORTALEZA   (Brazil)

^o Maggiore Hospital   (Italy)

^p NOVARTIS PHARMA AG   (Switzerland)

more..

Author keywords

Cyclosporine; Everolimus; Immunosuppressive regimen; Renal function; Therapeutic drug monitoring; Transplantation

Indexed keywords

ANTILIPEMIC AGENT; BASILIXIMAB; CORTICOSTEROID; CYCLOSPORIN A; EVEROLIMUS; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; RAPAMYCIN;

ACNE; ACUTE GRAFT REJECTION; ADULT; AGED; ANEMIA; ARTICLE; CANCER; CARDIOTOXICITY; CLINICAL TRIAL; CONCENTRATION RESPONSE; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; CREATININE BLOOD LEVEL; CYTOMEGALOVIRUS INFECTION; DIABETES MELLITUS; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; FEMALE; GASTROINTESTINAL DISEASE; HEMOLYTIC UREMIC SYNDROME; HERPES SIMPLEX; HUMAN; HYPERTENSION; INFECTION; KIDNEY BIOPSY; KIDNEY FUNCTION; KIDNEY GRAFT; LEUKOPENIA; LYMPHOCELE; MAJOR CLINICAL STUDY; MALE; PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SKIN DISEASE; SUBCUTANEOUS FAT DISORDER; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION;

ADULT; CYCLOSPORINE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY; KIDNEY TRANSPLANTATION; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; RANDOM ALLOCATION; RECEPTORS, INTERLEUKIN-2; SIROLIMUS; TIME FACTORS; TREATMENT OUTCOME;

EID: 11144357432     PISSN: 16006135     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1600-6143.2004.00389.x     Document Type: Article

References (35)

1. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, Mcintosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 96. N Engl J Med 2000; 342: 605-612.
2. Hariharan S, Mcbride MA, Cherikh WS, Tolleris CB, Bresnahan BA, Johnson CP. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 2002; 62: 311-318.
3. Kahan BD, Chang JY, Sehgal SN. Preclinical evaluation of a new potent immunosuppressive agent, rapamycin. Transplantation 1991; 52: 185-191.
4. Nashan B. Early clinical experience with a novel rapamycin derivative. Ther Drug Monit 2002; 24: 53-58.
5. Sehgal S. Rapamune (sirolimus, rapamycin): an overview and mechanism of action. Ther Drug Monit 1995; 17: 660-665.
6. Schuler W, Sedrani R, Cottens S et al. SDZ RAD, a new rapamycin derivative: pharmacologic properties in vitro and in vivo. Transplantation 1997; 64: 36-42.
7. Hausen B, Boeke K, Berry GJ, Segarra IT, Christians U, Morris RE. Suppression of acute rejection in allogenic rat lung transplantation: a study of the efficacy and pharmacokinetics of rapamycin derivative (SDZ RAD) used alone and in combination with a microemulsion formulation of cyclosporine. J Heart Lung Transplant 1999; 18: 150-159.
8. Schuurman H-J, Cottens S, Fuchs S et al. SDZ RAD, a new rapamycin derivative: synergism with cyclosporine. Transplantation 1997; 64: 32-35.
9. Serkova N, Hausen B, Berry GJ et al. Tissue distribution and clinical monitoring of the novel macrolide immunosuppressant SDZ-RAD and its metabolites in monkey lung transplant recipients: interaction with cyclosporine. J Pharmacol Exp Ther 2000; 294: 323-332.
10. Hausen B, Boeke K, Berry GJ et al. Coadministration of Neoral and the novel rapamycin analog, SDZ RAD, to rat lung allograft recipients: potentiation of immunosuppressive efficacy and improvement of tolerability by staggered simultaneous treatment. Transplantation 1999; 67: 956-962.
11. Vitko S, Margreiter R, Weimar W et al. and the RAD 201 Study Group. International, double-blind, parallel-group study of the safety and efficacy of Certican™ (RAD) versus mycophenolate mofetil (MMF) in combination with Neoral® and steroids. Am J Transplant 2001; 1 (Suppl. 1): 474, (Abstract) 1337.
12. Kaplan B, Tedesco-Silva H, Mendez R et al. and the RAD 251 Study Group. North/South American, double-blind, parallel group study of the safety and efficacy of Certican™ (RAD) versus mycophenolate mofetil (MMF) in combination with Neoral® and corticosteroids. Am J Transplant 2001; 1 (Suppl. 1): 475, (Abstract) 1339.
13. Curtis J, Nashan B, Ponticelli C et al. and the RAD 156 Study Group. One year results of a multicenter, open-label trial on safety, efficacy of Certican™ (RAD) used in combination with Simulect® corticosteroids and full or reduced dose Neoral® in renal transplantation. Am J Transplant 2001; 1 (Suppl. 1): 474, (Abstract) 1335.
14. Kovarik JM, Hsu C-H, Mcmahon L, Berthier S, Rordorf C. Population pharmacokinetics of everolimus in de novo renal transplant patients: impact of ethnicity and comedications. Clin Pharmacol Ther 2001; 70: 247-254.
15. Kovarik JM, Kaplan B, Tedesco-Silva H et al. Exposure-response relationships for everolimus in de novo kidney transplantation: defining a therapeutic range. Transplantation 2002; 73: 920-925.
16. Barama A, Perner F, Beauregard-Zollinger L, Prestele H. Absorption profiling of cyclosporine therapy for de novo kidney transplantation: a prospective, randomised study comparing sparse sampling to trough monitoring. Transplantation 2000; 69 (Suppl. 8): S162 (Abstract 19).
17. Halloran P, Helms LM, Kung L, Noujaim J. The temporal profile of calcineurin inhibition by cyclosporine in vivo. Transplantation 1999; 68: 1356-1361.
18. Sindhi R, Lavia MF, Paulling E et al. Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine + rapamycin regimen. Transplantation 2000; 69: 432-436.
19. Nankivell BJ, Gruenewald SM, Allen RD, Chapman JR. Predicting glomerular filtration rate after kidney transplantation. Transplantation 1995; 59: 1683-1689.
20. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
21. Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999; 55: 713-723.
22. Kahan BD, Julian BA, Pescovitz MD, Vanrenterghem Y, Neylan J. Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in Caucasian recipients of mis-matched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation 1999; 68: 1526-1532.
23. Kahan BD for The Rapamune US Study Group. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. Lancet 2000; 356: 194-202.
24. Macdonald AS, Rapamune Global Study Group. A worldwide, phase III, randomized, controlled safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. Transplantation 2001; 71: 271-280.
25. Podder H, Stepkowski SM, Napoli KL et al. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J Am Soc Nephrol 2001; 12: 1059-1071.
26. Johnson RWG, Kreis H, Oberbauer R, Brattström C, Claesson K, Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72: 777-786.
27. Basadonna GP, Matas AJ, Gillingham KJ et al. Early versus late acute renal allograft rejection: impact on chronic rejection. Transplantation 1993; 55: 993-995.
28. Leggat JE, Ojo AO, Leichtman AB et al. Long-term renal allograft survival: prognostic implication of the timing of acute rejection episodes. Transplantation 1997; 63: 1268-1272.
29. Oppenheimer F, Oyen O, Viljoen H, Vitko S, Falcone A, Cremer M. 36-month results of an international study with everolimus for the prevention of allograft rejection in de novo kidney transplant recipients. Am J Transplant 2003; 3 (Suppl. 5): 459 (Abstract).
30. Thervet E, Pfeffer P, Scolari MP et al. Clinical outcomes during the first 3 months post-transplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion (Neoral®). Transplantation 2003.
31. Libby P, Pober JS. Chronic rejection. Immunity 2001; 14: 387-397.
32. Jardine A. Assessing cardiovascular risk profile of immunosuppressive agents. Transplantation 2001; 72: S81-S88.
33. Margreiter R for the European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 2002; 359: 741-746.
34. Lebranchu Y, Bridoux F, Buchler M et al. Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am J Transplant 2002; 2: 48-56.
35. Lawen JG, Davies EA, Mourad G et al. Randomized double-blind study of immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with mycophenolate mofetil-containing triple therapy in renal transplantation. Transplantation 2003; 75: 37-43.