Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial

Calabresi, Peter A.; Radüe, Ernst Wilhelm; Goodin, Douglas S.; Jeffery, Douglas; Rammohan, Kottil; Reder, Anthony T.; Vollmer, Timothy; Agius, Mark; Kappos, Ludwig; Stites, Tracy; Li, Bingbing; Cappiello, Linda; Rosenstiel, Philipp von; Lublin, Fred

doi:10.1016/s1474-4422(14)70049-3

Cited by 760 publications

(797 citation statements)

References 13 publications

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“…Studies on MS disease activity, such as clinical drug trials, indicate that the number of new MRI lesions is approximately 4–12 times larger than the number of new clinical relapses during the same time period 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Such “clinically silent” MRI lesions stress the importance of monitoring patients with MRI even in the absence of clinical signs of disease activity.…”

Section: Resultsmentioning

confidence: 99%

“…While we acknowledge this and would like to emphasize that the MRI frequency and timing should be adapted to the clinical situation, it is our opinion that general recommendations of MRI frequency are still valuable in the clinical care of patients. The recommendations regarding MRI frequency presented here are based on clinical experience and extrapolation of study data on the level of disease activity seen in treated and untreated patients with MS in phase III studies 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20…”

Section: Resultsmentioning

confidence: 99%

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Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

et al. 2016

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Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

et al. 2016

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“…FTY was generally well tolerated in the aforementioned trials of up to 2 years' duration, with most adverse events (AE) being manageable and of mild‐to‐moderate severity 3, 4, 6. The cumulative datasets from clinical trials and their extensions, plus post‐marketing studies, have well delineated the safety profile of FTY in patients with RRMS 11…”

Section: Safety Profile Of Fingolimod Therapymentioning

confidence: 99%

“…Two large, phase III, double‐blind, randomized trials have shown superior efficacy of FTY compared with placebo (2‐year FREEDOMS and FREEDOMS II studies)3, 4 or i.m. IFN‐β1a (1‐year TRANSFORMS and extended TRANSFORMS studies) 5, 6.…”

Section: Clinical Utility Of Fingolimodmentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

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“…Fingolimod is a sphingosine 1‐phosphate (S1P) receptor modulator and exerts its therapeutic effects by modulating the S1P receptors expressed on peripheral lymphocytes 3, 4. The efficacy and safety profile of fingolimod has been well demonstrated in clinical trial programs and in real‐world settings 5, 6, 7, 8, 9, 10…”

Section: Introductionmentioning

confidence: 99%

Determination of Seminal Concentration of Fingolimod and Fingolimod‐Phosphate in Multiple Sclerosis Patients Receiving Chronic Treatment With Fingolimod

David

Berwick

Pezous

et al. 2017

Clinical Pharm in Drug Dev

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The safety profile of fingolimod 0.5 mg, approved therapy for relapsing multiple sclerosis, is well established in clinical and real‐world studies. As fingolimod is teratogenic in rats, it was considered important to assess the concentrations of fingolimod and its active metabolite, fingolimod‐phosphate, in the semen of male patients on treatment and the risk of harming a fetus in a pregnant partner. In this multicenter open‐label study, 13 male patients receiving fingolimod for at least 6 months provided 1 semen and 1 blood sample for analyte concentration measurements. The steady‐state seminal concentrations of fingolimod and fingolimod‐phosphate were close to those simultaneously observed in blood. The amount of fingolimod‐related material in 10 mL of ejaculate was estimated to be 47.5 ng. The estimated fingolimod and fingolimod‐phosphate blood Cmax values in a woman having regular sexual intercourse with a male patient treated with fingolimod 0.5 mg were approximately 400 and 2400 times smaller than the estimated values in the embryo‐fetal development study in rats at the no‐observed‐adverse‐event level. Consequently, the risk of harming a fetus in a pregnant woman is considered extremely unlikely.

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Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial

Cited by 760 publications

References 13 publications

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

Neurological safety of fingolimod: An updated review

Determination of Seminal Concentration of Fingolimod and Fingolimod‐Phosphate in Multiple Sclerosis Patients Receiving Chronic Treatment With Fingolimod

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