Article detail · 2010
A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis
- Year
- 2010
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue New England Journal of Medicine
- Catalog match (ISSN) New England Journal of Medicine
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
BACKGROUND: Oral fingolimod, a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with either placebo or intramuscular interferon beta-1a, in phase 2 and 3 studies of multiple sclerosis. METHODS: In our 24-month, double-blind, randomized study, we enrolled patients who had relapsing-remitting multiple sclerosis, were 18 to 55 years of age, had a score of 0 to 5.5 on the Expanded Disability Status Scale (which ranges from 0 to 10, with higher scores indicating greater disability), and had had one or more relapses in the previous year or two or more in the previous 2 years. Patients received oral fingolimod at a dose of 0.5 mg or 1.25 mg daily or placebo. End points included the annualized relapse rate (the primary end point) and the time to disability progression (a secondary end point). RESULTS: A total of 1033 of the 1272 patients (81.2%) completed the study. The annualized relapse rate was 0.18 with 0.5 mg of fingolimod, 0.16 with 1.25 mg of fingolimod, and 0.40 with placebo (P<0.001 for either dose vs. placebo). Fingolimod at doses of 0.5 mg and 1.25 mg significantly reduced the risk of disability progression over the 24-month period (hazard ratio, 0.70 and 0.68, respectively; P=0.02 vs. placebo, for both comparisons). The cumulative probability of disability progression (confirmed after 3 months) was 17.7% with 0.5 mg of fingolimod, 16.6% with 1.25 mg of fingolimod, and 24.1% with placebo. Both fingolimod doses were superior to placebo with regard to MRI-related measures (number of new or enlarged lesions on T(2)-weighted images, gadolinium-enhancing lesions, and brain-volume loss; P<0.001 for all comparisons at 24 months). Causes of study discontinuation and adverse events related to fingolimod included bradycardia and atrioventricular conduction block at the time of fingolimod initiation, macular edema, elevated liver-enzyme levels, and mild hypertension. CONCLUSIONS: As compared with placebo, both doses of oral fingolimod improved the relapse rate, the risk of disability progression, and end points on MRI. These benefits will need to be weighed against possible long-term risks. (ClinicalTrials.gov number, NCT00289978.)
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Citations
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2,648 citations
OpenAlex cited_by_count (cache / database)
81 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis 2011
- Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study 2018
- Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod subgroup analyses of the double blind randomised placebo controlled FREEDOMS study 2012
- Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study 2012
- Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study 2017
- Switch to natalizumab versus fingolimod in active relapsing–remitting multiple sclerosis 2014
- Impact of Fingolimod Therapy on Magnetic Resonance Imaging Outcomes in Patients With Multiple Sclerosis 2012
- Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis 2015
- Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years 2020
- Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years 2020