A Multicenter, Open Label Pilot Study of Early (5 Day) Corticosteroid Cessation in De Novo Renal Transplant Recipients Under Simulect, Tacrolimus, and Sirolimus Therapy: One Year Results

Woodle, E. Steve; Vincenti, F.; Lorber, M. I.; Gritsch, Albin; Hricik, Donald E.; Washburn, K. W.; Matas, A. J.; Gallichio, M

doi:10.1097/00007890-200407271-00443

Cited by 5 publications

(5 citation statements)

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“…The low rate of biopsy‐confirmed acute rejection episodes [44] was difficult to evaluate as steroid treatment was administered to additional recipients who did not undergo biopsies. Despite the initial enthusiasm for a SRL–TRL combination for primary immunosuppression, variable and frequently equivocal results have been noted in preliminary, retrospective, nonrandomized, or single‐arm treatment reports including small patient numbers [44–51]. Furthermore, the different concentration ranges and use of various other immunosuppressants (detailed in Tables 3 and 4) obfuscate any firm conclusion about this regimen [52–59].…”

Section: Sirolimus In Combination With Tacrolimus: Results Of Clinicamentioning

confidence: 99%

Clinical application of sirolimus in renal transplantation: an update

Chueh

Kahan

2005

Transplant Int

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Summary In addition to an analysis of the final results of phase I/II and phase III clinical trials of sirolimus (SRL), this review focuses on the recent results of several studies in renal transplantation, which include diverse combinations of SRL with other immunosuppressive agents. While SRL was initially introduced as an adjunctive agent to calcineurin inhibitors, it is now serving as the base for therapies that spare or avoid these nephrotoxic drugs. However, to optimize the use of SRL as base therapy, further work is necessary to determine target concentrations, requirement for concomitant steroids and/or nucleoside synthesis blockers, and countermeasure therapy to overcome the drug's adverse effects.

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Section: Sirolimus In Combination With Tacrolimus: Results Of Clinicamentioning

confidence: 99%

Clinical application of sirolimus in renal transplantation: an update

Chueh

Kahan

2005

Transplant Int

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“…A number of studies over the past several years have demonstrated the ability of new, potent immunosuppressive agents (mycophenolate mofetil (MMF), tacrolimus and sirolimus) to allow intermediate (within 3-6 months posttransplant) or early CSWD (i.e. within the first month posttransplant), or following tacrolimus rescue therapy for refractory rejection (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Moreover, experiences from other studies have indicated that induction therapy with potent T cell depleting antibodies can ablate the increased risk of acute rejection with CSWD (14).…”

Section: Introductionmentioning

confidence: 99%

“…Our experience with early CSWD began in December 1995 (15) and has consisted of several studies that included enrollment of patients with one or more immunologic risk factors for acute rejection including African Americans (15)(16)(17)(18)(19)(20). In addition, we have conducted pilot studies in which only high immunologic risk patients, or patients with DGF (17,18), were enrolled.…”

Section: Introductionmentioning

confidence: 99%

Multivariate Analysis of Risk Factors for Acute Rejection in Early Corticosteroid Cessation Regimens Under Modern Immunosuppression

Woodle

Alloway

Buell

et al. 2005

American Journal of Transplantation

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The purpose of this study was to define risk factors for acute rejection with early corticosteroid withdrawal (CSWD; within 7 days posttransplant) in renal transplantation. Data from prospective, IRBapproved early CSWD trials were analyzed. Overall acute rejection rate in 308 patients was 17.1%. Acute rejection rates and observed risks (OR) in patients with individual risk factors were: repeat transplants 38.6%; current PRA >25%; 29.4%; African Americans 23.5%; delayed graft function (DGF) 26.1%; HLA DR mismatches >0 17.9%; female gender 19.7%; Thymoglobulin induction 15.3%; type 1 diabetes 30.8%; type 2 diabetes 11.1%; deceased donor recipients 21%; and living donor recipients 14%. Logistic regression analysis provided the following risks (OR) for acute rejection: repeat transplant 2.51; current PRA > 25% 1.53; African Americans 1.47; DGF 1.58; HLA DR mismatches > 0 1.61; female gender 1.43; Thymoglobulin induction 0.61; type 1 diabetes 2.23, type 2 diabetes 0.5, deceased donor recipients 1.11, and living donor recipients 0.9. Risk factors for acute rejection under early corticosteroid withdrawal are similar to those previously defined under chronic corticosteroid therapy. These observations provide implications for future CSWD trials including: use of T cell depleting antibody induction therapy (thymoglobulin) to reduce acute rejection risk, 2) enrollment stratification for high risk groups, and 3) modified immunosuppression for high risk groups.

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“…Corticosteroid-minimization with IL-2 receptor antagonists was also investigated using sirolimus-containing regimens. A multicenter, open-label pilot study in renal transplant patients evaluated a regimen of basiliximab, tacrolimus and sirolimus with corticosteroids tapered rapidly from day 1 to day 4 after transplantation, then discontinued [28]. Eighty per cent of patients continued to receive corticosteroid-free immunosuppression at 6 months, with a 100% patient and graft survival.…”

Section: Early Corticosteroid Withdrawal Using An 11-2 Receptor Antagmentioning

confidence: 99%

Interleukin-2 receptor antagonists and aggressive steroid minimization strategies for kidney transplant patients

Vincenti

2004

Transpl Int

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Steroid withdrawal during the first week after transplantation surgery, or complete avoidance of steroids, offers potential benefits. The interleukin-2 (IL-2) receptor antibodies, basiliximab and daclizumab, can enable aggressive steroid minimization protocols that are efficacious while reducing toxicity. A multicenter, randomized trial of kidney transplant recipients has shown the incidence of biopsy-proven acute rejection with basiliximab, cyclosporine and mycophenolate mofetil with steroids withdrawn at day 5 to be similar to a conventional triple-therapy regimen. A single perioperative dose of corticosteroids with an IL-2 receptor antagonist also seems as efficacious as standard steroid therapy. Corticosteroid-minimization with IL-2 receptor antagonists has also been investigated with sirolimus-containing regimens and has shown excellent outcomes. Experience with complete steroid avoidance, using an IL-2 receptor antagonist, is limited, but initial results are promising, particularly in pediatric patients. Administration of an IL-2 receptor antagonist with aggressive steroid minimization in selected, well-monitored patients seems reasonable, but further trials are required to define optimal protocols.

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A Multicenter, Open Label Pilot Study of Early (5 Day) Corticosteroid Cessation in De Novo Renal Transplant Recipients Under Simulect, Tacrolimus, and Sirolimus Therapy: One Year Results

Cited by 5 publications

References 0 publications

Clinical application of sirolimus in renal transplantation: an update

Clinical application of sirolimus in renal transplantation: an update

Multivariate Analysis of Risk Factors for Acute Rejection in Early Corticosteroid Cessation Regimens Under Modern Immunosuppression

Interleukin-2 receptor antagonists and aggressive steroid minimization strategies for kidney transplant patients

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