Sökning: onr:"swepub:oai:gup.ub.gu.se/266136" > Siponimod versus pl...
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000 | 08119naa a2201477 4500 | |
001 | oai:gup.ub.gu.se/266136 | |
003 | SwePub | |
008 | 240910s2018 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:137940861 | |
024 | 7 | a https://gup.ub.gu.se/publication/2661362 URI |
024 | 7 | a https://doi.org/10.1016/S0140-6736(18)30475-62 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1379408612 URI |
040 | a (SwePub)gud (SwePub)ki | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Kappos, Ludwig4 aut |
245 | 1 0 | a Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study |
264 | 1 | c 2018 |
520 | a © 2018 Elsevier Ltd 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 treatme nt 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 occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
700 | 1 | a Bar-Or, Amit4 aut |
700 | 1 | a Cree, Bruce A.C.4 aut |
700 | 1 | a Fox, Robert J.4 aut |
700 | 1 | a Giovannoni, Gavin4 aut |
700 | 1 | a Gold, Ralf4 aut |
700 | 1 | a Vermersch, Patrick4 aut |
700 | 1 | a Arnold, Douglas L.4 aut |
700 | 1 | a Arnould, Sophie4 aut |
700 | 1 | a Scherz, Tatiana4 aut |
700 | 1 | a Wolf, Christian4 aut |
700 | 1 | a Wallström, Erik4 aut |
700 | 1 | a Dahlke, Frank4 aut |
700 | 1 | a Achiron, Anat4 aut |
700 | 1 | a Achtnichts, Lutz4 aut |
700 | 1 | a Agan, Kadriye4 aut |
700 | 1 | a Akman-Demir, Gulsen4 aut |
700 | 1 | a Allen, Alison B.4 aut |
700 | 1 | a Antel, Jack P.4 aut |
700 | 1 | a Antiguedad, Alfredo Rodriguez4 aut |
700 | 1 | a Apperson, Michelle4 aut |
700 | 1 | a Applebee, Angela M.4 aut |
700 | 1 | a Ayuso, Guillermo Izquierdo4 aut |
700 | 1 | a Baba, Masayuki4 aut |
700 | 1 | a Bajenaru, Ovidiu4 aut |
700 | 1 | a Balasa, Rodica4 aut |
700 | 1 | a Balci, Belgin Petek4 aut |
700 | 1 | a Barnett, Michael4 aut |
700 | 1 | a Bass, Ann4 aut |
700 | 1 | a Becker, Veit U.4 aut |
700 | 1 | a Bejinariu, Mihaela4 aut |
700 | 1 | a Bergh, Florian Then4 aut |
700 | 1 | a Bergmann, Arnfin4 aut |
700 | 1 | a Bernitsas, Evanthia4 aut |
700 | 1 | a Berthele, Achim4 aut |
700 | 1 | a Bhan, Virender4 aut |
700 | 1 | a Bischof, Felix4 aut |
700 | 1 | a Bjork, Randall John4 aut |
700 | 1 | a Blevins, Gregg4 aut |
700 | 1 | a Boehringer, Matthias4 aut |
700 | 1 | a Boerner, Thomas4 aut |
700 | 1 | a Bonek, Robert4 aut |
700 | 1 | a Bowen, James D.4 aut |
700 | 1 | a Bowling, Allen4 aut |
700 | 1 | a Boyko, Alexey N.4 aut |
700 | 1 | a Boz, Cavit4 aut |
700 | 1 | a Bracknies, Vera4 aut |
700 | 1 | a Braune, Stefan4 aut |
700 | 1 | a Brescia Morra, Vincenzo4 aut |
700 | 1 | a Brochet, Bruno4 aut |
700 | 1 | a Brola, Waldemar4 aut |
700 | 1 | a Brownstone, Paul Kenneth4 aut |
700 | 1 | a Brozman, Miroslav4 aut |
700 | 1 | a Brunet, Donald4 aut |
700 | 1 | a Buraga, Ioan4 aut |
700 | 1 | a Burnett, Margaret4 aut |
700 | 1 | a Buttmann, Mathias4 aut |
700 | 1 | a Butzkueven, Helmut4 aut |
700 | 1 | a Cahill, Jonathan4 aut |
700 | 1 | a Calkwood, Jonathan C.4 aut |
700 | 1 | a Camu, William4 aut |
700 | 1 | a Cascione, Mark4 aut |
700 | 1 | a Castelnovo, Giovani4 aut |
700 | 1 | a Centonze, Diego4 aut |
700 | 1 | a Cerqueira, Joao4 aut |
700 | 1 | a Chan, Andrew4 aut |
700 | 1 | a Cimprichova, Andrea4 aut |
700 | 1 | a Cohan, Stanley4 aut |
700 | 1 | a Comi, Giancarlo4 aut |
700 | 1 | a Conway, Jill4 aut |
700 | 1 | a Cooper, Joanna A.4 aut |
700 | 1 | a Corboy, John4 aut |
700 | 1 | a Correale, Jorge4 aut |
700 | 1 | a Costell, Brian4 aut |
700 | 1 | a Cottrell, David A.4 aut |
700 | 1 | a Coyle, Patricia K.4 aut |
700 | 1 | a Craner, Matthew4 aut |
700 | 1 | a Cui, Liying4 aut |
700 | 1 | a Cunha, Luis4 aut |
700 | 1 | a Czlonkowska, Anna4 aut |
700 | 1 | a da Silva, Ana Martins4 aut |
700 | 1 | a de Sa, Joao4 aut |
700 | 1 | a de Seze, Jérôme4 aut |
700 | 1 | a Debouverie, Marc4 aut |
700 | 1 | a Debruyne, Jan4 aut |
700 | 1 | a Decoo, Danny4 aut |
700 | 1 | a Defer, Gilles4 aut |
700 | 1 | a Derfuss, Tobias4 aut |
700 | 1 | a Deri, Norma H.4 aut |
700 | 1 | a Dihenia, Bhupesh4 aut |
700 | 1 | a Dioszeghy, Peter4 aut |
700 | 1 | a Donath, Vladimir4 aut |
700 | 1 | a Dubois, Benedicte4 aut |
700 | 1 | a Duddy, Martin4 aut |
700 | 1 | a Duquette, Pierre4 aut |
700 | 1 | a Edan, Gilles4 aut |
700 | 1 | a Efendi, Husnu4 aut |
700 | 1 | a Elias, Stanton4 aut |
700 | 1 | a Lycke, Jan,d 1956u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xlycja |
710 | 2 | a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi4 org |
773 | 0 | t The Lancetg 391, s. 1263-1273q 391<1263-1273x 0140-6736x 1474-547X |
856 | 4 8 | u https://gup.ub.gu.se/publication/266136 |
856 | 4 8 | u https://doi.org/10.1016/S0140-6736(18)30475-6 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:137940861 |
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