Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.
Details
Serval ID
serval:BIB_A14B68C4B829
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.
Journal
Archives of Neurology
Working group(s)
FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) Study Group
Contributor(s)
Calandra T., DiMarco J., Easton JD., Hudson LD., Kesselring J., Laupacis A., Temkin N., Weinshenker BG., Zarbin M., Calabresi P., Hohlfeld R., Kappos L., O'Connor P., Polman C., Beran R., Paine M., MacDonell R., Heard R., Boundy K., Van Opdenbosch L., Bartholomé E., Pandololfo M., Seeldrayers P., Dubois B., Vande Gaer L., Decoo D., Mulleners E., Bhan V., Brunet D., Kremenchutzky M., Selchen DH., Lachapelle J., Christie S., Veloso F., Devonshire V., Rektor I., Ondrich V., Kanovsky P., Zapletalová O., Ambler Z., Ehler E., Meluzinova E., Havrdová E., Pazdera L., Vysata O., Vachova M., Gross-Paju K., Kallela M., Kinnunen E., Sumelahti ML., Eralinna JP., Airas L., Clavelou P., Moreau T., Vermersch P., Pelletier J., Camu W., Damier P., Wiertlewski S., Labauge P., Gout O., Lubetzki C., Edan G., De Seze J., Menck S., Haas J., Einhäupl M., Harms L., Wandinger KP., Zipp F., Kieseier B., Anders D., Berghoff M., Oschmann P., Rosenkranz T., Heesen C., Bergh FT., Sailer M., Hohlfeld R., Bischoff F., Marziniak M., Muller M., Kleiter I., Steinbrecher A., Kowalik A., Melms A., Weissert R., Wiendl H., Karageorgiou C., Fakas N., Maltezou M., Mitsikostas D., Káposzta Z., Rozsa C., Valikovics A., Kerényi L., Hutchinson M., Milo R., Miller A., Shahien R., Achiron A., Polman C., Frequin S., Jongen P., Zwanikken C., Hintzen R., Anten B., Hupperts R., Visser L., Kochanowicz J., Drozdowski W., Fryze W., Wajgt A., Selmaj K., Kozubski W., Dorobek M., Pniewski J., Czlonkowska A., Kwiecinski H., Stepien A., Panea C., Boeru G., Perju-Dumbrava L., Zaharia C., Popescu CD., Balasa R., Bejenaru O., Yakupov EZ., Yakhhno N., Kotov S., Shmyrev V., Zavalishin I., Elchaninov AP., Stolyarov I., Odinak M., Turcani P., Kurča E., Vyletĕlka J., Heckman J., Isaacs M., Coetzee C., Lycke J., Hillert J., Olsson T., Kappos L., Gugleta K., Sturzenegger R., Schluep M., Goebels N., Linnebank M., Irkec C., Karabudak R., Turan OF., Neyal M., Işik N., Sutlas PN., Akman-Demir G., Siva A., Idiman E., Kocaman A., Zorlu Y., Sevim S., Cottrell D., Silber E., Barnes D., Bates D., Constantinescu C., Sharrack B., Bendfeldt K., Radue EW.
ISSN
1538-3687 (Electronic)
ISSN-L
0003-9942
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
69
Number
10
Pages
1259-1269
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't Publication Status: ppublish. pdf type: clinical trials
Abstract
OBJECTIVE: To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study.
DESIGN: Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics.
SETTING: Worldwide, multicenter clinical trial.
PATIENTS: Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272).
MAIN OUTCOME MEASURES: We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume.
RESULTS: Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability.
CONCLUSION: These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00289978
DESIGN: Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics.
SETTING: Worldwide, multicenter clinical trial.
PATIENTS: Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272).
MAIN OUTCOME MEASURES: We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume.
RESULTS: Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability.
CONCLUSION: These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00289978
Keywords
Administration, Oral, Adolescent, Adult, Brain/drug effects, Brain/pathology, Disability Evaluation, Dose-Response Relationship, Drug, Double-Blind Method, Encephalitis/drug therapy, Encephalitis/etiology, Female, Gadolinium/diagnostic use, Humans, Immunosuppressive Agents/therapeutic use, International Cooperation, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis/complications, Multiple Sclerosis/drug therapy, Outcome Assessment (Health Care), Propylene Glycols/therapeutic use, Sphingosine/analogs & derivatives, Sphingosine/therapeutic use, Time Factors, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
30/01/2014 16:24
Last modification date
20/08/2019 16:07
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