Randomized Controlled Trial of FTY720 Versus MMF in De Novo Renal Transplantation

Tedesco‐Silva, Hélio; Pescovitz, Mark D.; Cibrik, Diane M.; Rees, Michael; Mulgaonkar, Shamkant; Kahan, Barry D.; Gugliuzza, Kristene; Rajagopalan, P. R.; Esmeraldo, Ronaldo de Matos; Lord, Hélène; Salvadori, Maurizio; Slade, Jennifer M.

doi:10.1097/01.tp.0000251718.95622.b3

Cited by 104 publications

(58 citation statements)

References 17 publications

(17 reference statements)

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“…The clinical trials assessing the use of fingolimod as an antirejection agent in renal transplant patients was reported by Salvadori et al 27 and Tedesco-Silva et al 28 Both these clinical trials evaluated higher-dose fingolimod (5 and 2.5 mg) in association with cyclosporine, and both reported higher rates of macular oedema (Salvadori et al: 2.2% at 5 mg dose, 1.3% at 2.5 mg dose), (Tedesco-Silva et al: 3.4% at 5 mg dose and 1.7% at 2.5 mg). Tedesco-Silva and Salvadori did not exclude patients with diabetes in the sample population.…”

Section: Fame and Its Association With Diabetesmentioning

confidence: 99%

“…25,26 Incidence of FAME Macular oedema has been a well-documented side effect of fingolimod since it was originally evaluated as an anti-rejection agent for renal transplantation. 27,28 Fingolimodassociated macular oedema was therefore monitored for and reported in the initial clinical trials investigating the efficacy of fingolimod for RRMS. The FREEDOMS study was a phase III multicentre, 24-month, double blind randomised study comparing 0.5 mg (n = 425) and 1.25 mg (n = 429) fingolimod daily treatment with placebo (n = 418) in patients with RRMS.…”

Section: Fingolimod and The Eyementioning

confidence: 99%

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Fingolimod: therapeutic mechanisms and ocular adverse effects

Mandal

Gupta

Fusi-Rubiano

et al. 2016

Eye

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Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity.

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Section: Fame and Its Association With Diabetesmentioning

confidence: 99%

Section: Fingolimod and The Eyementioning

confidence: 99%

Fingolimod: therapeutic mechanisms and ocular adverse effects

Mandal

Gupta

Fusi-Rubiano

et al. 2016

Eye

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“…Unexpectedly, both FTY720 treatment arms were associated with lower creatinine clearance and higher incidence of macular edema. 56,57 These results, unexplained but believed to be attributable to nonimmunological renal toxicity, indicated that FTY720 provided no benefit in comparison to standard care and resulted in temporary stopping of the development of FTY720 for renal transplantation.…”

Section: Fingolimod (Fty720)mentioning

confidence: 98%

Emerging Therapies for Multiple Sclerosis

Muraro

Bielekova

2007

Neurotherapeutics

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Summary:This review examines the mode of action, safety profile and clinical efficacy of some of the most promising new therapeutic strategies for multiple sclerosis. Autologous hematopoietic stem cell transplantation can regenerate a new and tolerant immune system and is a potentially effective rescue therapy in a subset of patients with aggressive forms of MS refractory to approved immunomodulatory and immunosuppressive agents. High-dose cyclophosphamide without stem cell support is suggested to induce prolonged remissions through similar immunological mechanisms with less toxicity. Fingolimod (FTY720) is a novel oral immunomodulating agent that acts through preventing lymphocyte recirculation from lymphoid organs. Monoclonal antibody therapy has provided scientists and clinicians the opportunity to rationally direct the therapeutic intervention against specific molecules. Targeting molecules of the immune system such as CD52 (alemtuzumab), CD25 (daclizumab), VLA-4 (natalizumab) and CD20 (rituximab) have resulted in potent immunomodulatory effects through sometimes unpredicted mechanisms. The potential of immunoglobulins to induce remyelination in the CNS is being investigated in an attempt to develop therapies promoting tissue repair and functional recovery. The evidence supporting the potential of these emerging immunotherapies suggests that strong progress is being made in the development of effective cures for multiple sclerosis.

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“…In these studies, fingolimod was associated with the development of macular edema (ME). 4 As a result of this important incidental finding, monitoring of ME was implemented in subsequent trials involving fingolimod in MS.…”

Section: Discussionmentioning

confidence: 99%

Fingolimod and macular edema

et al. 2014

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SummaryFingolimod causes macular edema (ME) by acting via the S1P3 receptor agonism, thereby reducing the tight junction between the endothelial cells of the retinal capillaries. This results in the breakdown of the inner blood retinal barrier, causing ME. Ophthalmologic evaluation including optical coherence tomography is recommended at baseline and then at 3 months, 6 months, and annually thereafter in all patients on fingolimod. The risk of ME increases in patients who are diabetic, have had uveitis, or who undergo intraocular procedures such as cataract surgery, and hence these patients need close monitoring. Cessation of the drug results in resolution of the ME. However, ME can also be treated using anti-inflammatory medication (steroids) in patients who opt to remain on fingolimod.F ingolimod is the first oral disease-modifying therapy approved for the treatment of multiple sclerosis (MS). The efficacy of fingolimod has been demonstrated in 2 large, phase III, double-blind, randomized trials.1,2 Practical aspects related to the use of fingolimod and its systemic side effects have been described. 3Fingolimod was used initially as an immunomodulator to augment the immunosuppressive effect of other drugs in renal transplant rejection. The dosage for renal transplant ranged between 2.5 and 5 mg, 5 and 10 times that approved for treatment of MS. Fingolimod failed to show a benefit for the prevention of renal allograft rejection over the conventional treatment in large phase III studies and hence further development in renal transplantation was stopped. In these studies, fingolimod was associated with the development of macular edema (ME).4 As

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Randomized Controlled Trial of FTY720 Versus MMF in De Novo Renal Transplantation

Abstract: While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

Cited by 104 publications

References 17 publications

Fingolimod: therapeutic mechanisms and ocular adverse effects

Fingolimod: therapeutic mechanisms and ocular adverse effects

Emerging Therapies for Multiple Sclerosis

Fingolimod and macular edema

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