Background and rationale for mechanism of action, efficacy, and safety of fingolimod (Gilenya), the first oral therapy for remitting-relapsing multiple sclerosis

Wills Eye Institute Neuro-Ophthalmology Service, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Current opinion in ophthalmology (Impact Factor: 2.5). 09/2011; 22(6):447-50. DOI: 10.1097/ICU.0b013e32834be03b
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    • "In phase 2, phase 3, and extension studies, fingolimod exhibited a relatively good safety and tolerability profile. Most commonly reported adverse events in the fingolimod group were mild infections, mainly of the lower respiratory tract, increased alanine aminotransferase levels, bradycardia, first and second degree atrioventricular blocks at the time of first administration, hypertension, macular edema, mild decrease in lung function, and lowering of peripheral blood lymphocyte count, as expected from the mechanism of action of fingolimod [11] [12] [13]. The European Medicines Agency (EMA) approved fingolimod as a single agent disease modifying therapy in patients with unsatisfactory disease control despite treatment with a beta interferon or in treatment-na¨ıve patients with rapidly evolving severe multiple sclerosis, providing a second-line treatment option in highly active RRMS. "
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    ABSTRACT: Objective . The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods . One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results . Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions . Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.
    06/2015; 2015(2). DOI:10.1155/2015/763418
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    ABSTRACT: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and is the common cause of optic neuritis. Fingolimod, an immunosuppressive agent, is used in MS to prevent acute exacerbations. We report a case of relapsing-remitting MS treated with fingolimod. The patient presented with an acute decrease in vision in the left eye. Eye examination showed clinical macular edema (ME) in the left eye, which was confirmed on fluorescein angiogram and optical coherence tomography (OCT). After discontinuation of fingolimod and treatment with topical corticosteroid medication, there was complete resolution of the ME. The ME as a side-effect of fingolimod is reversible after discontinuing, which was seen on OCT.
    Journal of Neurology 02/2012; 259(2):386-8. DOI:10.1007/s00415-011-6367-4 · 3.38 Impact Factor
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    ABSTRACT: The pathophysiology of multiple sclerosis (MS) is typically characterised by inflammation and demyelination leading to neurodegeneration, which is associated with disability and the progressive stages of MS. The visual system is a valuable tool for studying neurodegeneration and potential neuroprotection in the central nervous system due to its ease of accessibility. Optical coherence tomography (OCT) is a non-invasive tool, which can be used to measure the thickness of the retinal nerve fibre layer (RNFL). The thickness of RNFL is reduced following the development of MS and optic neuritis and can therefore be used as a correlate of global axonal loss. OCT is currently being investigated as a structural outcome measure for neuroprotective clinical trials of MS. This review describes the relationship between MS and optic neuritis and the associated RNFL thinning, the technology and advancements of OCT, the role of OCT in clinical trials for new neuroprotective therapies in MS and the future role of OCT in MS research.
    CNS & neurological disorders drug targets 05/2012; 11(5):518-27. DOI:10.2174/187152712801661185 · 2.63 Impact Factor