دورية أكاديمية
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
| العنوان: | Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study |
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| المؤلفون: | Kappos L., Bar-Or A., Cree B. A. C., Fox R. J., Giovannoni G., Gold R., Vermersch P., Arnold D. L., Arnould S., Scherz T., Wolf C., Wallstrom E., Dahlke F., Achiron A., Achtnichts L., Agan K., Akman-Demir G., Allen A. B., Antel J. P., Antiguedad A. R., Apperson M., Applebee A. M., Ayuso G. I., Baba M., Bajenaru O., Balasa R., Balci B. P., Barnett M., Bass A., Becker V. U., Bejinariu M., Bergh F. T., Bergmann A., Bernitsas E., Berthele A., Bhan V., Bischof F., Bjork R. J., Blevins G., Boehringer M., Boerner T., Bonek R., Bowen J. D., Bowling A., Boyko A. N., Boz C., Bracknies V., Braune S., Brescia Morra V., Brochet B., Brola W., Brownstone P. K., Brozman M., Brunet D., Buraga I., Burnett M., Buttmann M., Butzkueven H., Cahill J., Calkwood J. C., Camu W., Cascione M., Castelnovo G., Centonze D., Cerqueira J., Chan A., Cimprichova A., Cohan S., Comi G., Conway J., Cooper J. A., Corboy J., Correale J., Costell B., Cottrell D. A., Coyle P. K., Craner M., Cui L., Cunha L., Czlonkowska A., da Silva A. M., de Sa J., de Seze J., Debouverie M., Debruyne J., Decoo D., Defer G., Derfuss T., Deri N. H., Dihenia B., Dioszeghy P., Donath V., Dubois B., Duddy M., Duquette P., Edan G., Efendi H., Elias S., Emrich P. J., Estruch B. C., Evdoshenko E. P., Faiss J., Fedyanin A. S., Feneberg W., Fermont J., Fernandez O. F., Ferrer F. C., Fink K., Ford H., Ford C., Francia A., Freedman M., Frishberg B., Galgani S., Garmany G. P., Gehring K., Gitt J., Gobbi C., Goldstick L. P., Gonzalez R. A., Grandmaison F., Grigoriadis N., Grigorova O., Grimaldi L. M. E., Gross J., Gross-Paju K., Gudesblatt M., Guillaume D., Haas J., Hancinova V., Hancu A., Hardiman O., Harmjanz A., Heidenreich F. R., Hengstman G. J. D., Herbert J., Herring M., Hodgkinson S., Hoffmann O. M., Hofmann W. E., Honeycutt W. D., Hua L. H., Huang D., Huang Y., Hupperts R., Imre P., Jacobs A. K., Jakab G., Jasinska E., Kaida K., Kalnina J., Kaprelyan A., Karelis G., Karussis D., Katz A., Khabirov F. A., Khatri B., Kimura T., Kister I., Kizlaitiene R., Klimova E., Koehler J., Komatineni A., Kornhuber A., Kovacs K., Koves A., Kozubski W., Krastev G., Krupp L. B., Kurca E., Lassek C., Laureys G., Lee L., Lensch E., Leutmezer F., Li H., Linker R. A., Linnebank M., Liskova P., Llanera C., Lu J., Lutterotti A., Lycke J., Macdonell R., Maciejowski M., Maeurer M., Magzhanov R. V., Maida E. -M., Malciene L., Mao-Draayer Y., Marfia G. A., Markowitz C., Mastorodimos V., Matyas K., Meca-Lallana J., Merino J. A. G., Mihetiu I. G., Milanov I., Miller A. E., Millers A., Mirabella M., Mizuno M., Montalban X., Montoya L., Mori M., Mueller S., Nakahara J., Nakatsuji Y., Newsome S., Nicholas R., Nielsen A. S., Nikfekr E., Nocentini U., Nohara C., Nomura K., Odinak M. M., Olsson T., van Oosten B. W., Oreja-Guevara C., Oschmann P., Overell J., Pachner A., Panczel G., Pandolfo M., Papeix C., Patrucco L., Pelletier J., Piedrabuena R., Pless M., Polzer U., Pozsegovits K., Rastenyte D., Rauer S., Reifschneider G., Rey R., Rizvi S. A., Robertson D., Rodriguez J. M., Rog D., Roshanisefat H., Rowe V., Rozsa C., Rubin S., Rusek S., Sacca F., Saida T., Salgado A. V., Sanchez V. E. F., Sanders K., Satori M., Sazonov D. V., Scarpini E. A., Schlegel E., Schluep M., Schmidt S., Scholz E., Schrijver H. M., Schwab M., Schwartz R., Scott J., Selmaj K., Shafer S., Sharrack B., Shchukin I. A., Shimizu Y., Shotekov P., Siever A., Sigel K. -O., Silliman S., Simo M., Simu M., Sinay V., Siquier A. E., Siva A., Skoda O., Solomon A., Stangel M., Stefoski D., Steingo B., Stolyarov I. D., Stourac P., Strassburger-Krogias K., Strauss E., Stuve O., Tarnev I., Tavernarakis A., Tello C. R., Terzi M., Ticha V., Ticmeanu M., Tiel-Wilck K., Toomsoo T., Tubridy N., Tullman M. J., Tumani H., Turcani P., Turner B., Uccelli A., Urtaza F. J. O., Vachova M., Valikovics A., Walter S., Van Wijmeersch B., Vanopdenbosch L., Weber J. R., Weiss S., Weissert R., West T., Wiendl H., Wiertlewski S., Wildemann B., Willekens B., Visser L. H., Vorobeychik G., Xu X., Yamamura T., Yang Y. N., Yelamos S. M., Yeung M., Zacharias A., Zelkowitz M., Zettl U., Zhang M., Zhou H., Zieman U., Ziemssen T. |
| المساهمون: | Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C. |
| بيانات النشر: | Lancet Publishing Group NEW YORK |
| سنة النشر: | 2018 |
| المجموعة: | Università degli Studi di Genova: CINECA IRIS |
| الوصف: | Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS.Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3.0-6.5 were randomly assigned (2: 1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials. gov, number NCT01665144.Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16.8 years (SD 8.3), and the mean time since conversion to SPMS was 3.8 years (SD 3.5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0.79, 95% CI 0.65-0.95; relative risk reduction 21%; p=0.013). Adverse events ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/29576505; info:eu-repo/semantics/altIdentifier/wos/WOS:000428791600025; volume:391 (10127); firstpage:1263; lastpage:1273; numberofpages:11; journal:THE LANCET; http://hdl.handle.net/11567/977935Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85044304126 |
| DOI: | 10.1016/S0140-6736(18)30475-6 |
| الإتاحة: | https://doi.org/10.1016/S0140-6736Test(18)30475-6 http://hdl.handle.net/11567/977935Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.24955A07 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/S0140-6736(18)30475-6 |
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