Siponimod for the treatment of secondary progressive multiple sclerosis

被引:32
作者
Dumitrescu, Laura [1 ]
Constantinescu, Cris S. [2 ]
Tanasescu, Radu [1 ,2 ]
机构
[1] Univ Med & Pharm Carol Davila, Colentina Hosp, Dept Neurol, Dept Neurosci, Bucharest, Romania
[2] Univ Nottingham, Acad Clin Neurol, Div Clin Neurosci, Nottingham, England
关键词
BAF312; disease-modifying therapies; multiple sclerosis; progressive multiple sclerosis; siponimod; sphingosine; 1-phosphate; DISEASE-MODIFYING THERAPIES; SPHINGOSINE; 1-PHOSPHATE; INTERFERON BETA-1B; ORAL FINGOLIMOD; DOUBLE-BLIND; FOLLOW-UP; PATIENT; BAF312; PLACEBO; SPHINGOSINE-1-PHOSPHATE;
D O I
10.1080/14656566.2018.1551363
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Multiple sclerosis (MS) is a chronic central nervous system immune-mediated disease with an important inflammatory component associated with focal demyelination and widespread neurodegeneration. In most cases, the clinical presentation is relapsing-remitting, followed by a secondary progressive phase, characterized by disability accrual unrelated to relapses. In a minority, the phenotype is progressive from the beginning. Major therapeutic achievements have been made concerning the relapsing phase but modifying the evolution of progressive MS remains an unmet need. Areas covered: This review covers siponimod (BAF312), a new sphingosine 1-phosphate receptor modulator, and its role in the treatment of secondary progressive MS. The authors reviewed PubMed English literature using the keywords 'siponimod' or 'BAF312' and 'multiple sclerosis.' They also present the pharmacological profile of siponimod, as well as clinical efficacy and safety, with emphasis on the recently published results of a Phase III trial. Phase II data in relapsing MS are also summarized. Expert opinion: Siponimod may reduce the activity of the disease and has a modest effect on the gradual disability accrual. If approved, it may become one of the few available therapy options for secondary progressive MS.
引用
收藏
页码:143 / 150
页数:8
相关论文
共 54 条
[31]   Evidence for a two-stage disability progression in multiple sclerosis [J].
Leray, Emmanuelle ;
Yaouanq, Jacqueline ;
Le Page, Emmanuelle ;
Coustans, Marc ;
Laplaud, David ;
Oger, Joel ;
Edan, Gilles .
BRAIN, 2010, 133 :1900-1913
[32]   Defining the clinical course of multiple sclerosis: Results of an international survey [J].
Lublin, FD ;
Reingold, SC .
NEUROLOGY, 1996, 46 (04) :907-911
[33]   Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial [J].
Lublin, Fred ;
Miller, David H. ;
Freedman, Mark S. ;
Cree, Bruce A. C. ;
Wolinsky, Jerry S. ;
Weiner, Howard ;
Lubetzki, Catherine ;
Hartung, Hans-Peter ;
Montalban, Xavier ;
Uitdehaag, Bernard M. J. ;
Merschhemke, Martin ;
Li, Bingbing ;
Putzki, Norman ;
Liu, Fonda C. ;
Haering, Dieter A. ;
Kappos, Ludwig .
LANCET, 2016, 387 (10023) :1075-1084
[34]   Defining the clinical course of multiple sclerosis The 2013 revisions [J].
Lublin, Fred D. ;
Reingold, Stephen C. ;
Cohen, Jeffrey A. ;
Cutter, Gary R. ;
Sorensen, Per Soelberg ;
Thompson, Alan J. ;
Wolinsky, Jerry S. ;
Balcer, Laura J. ;
Banwell, Brenda ;
Barkhof, Frederik ;
Bebo, Bruce, Jr. ;
Calabresi, Peter A. ;
Clanet, Michel ;
Comi, Giancarlo ;
Fox, Robert J. ;
Freedman, Mark S. ;
Goodman, Andrew D. ;
Inglese, Matilde ;
Kappos, Ludwig ;
Kieseier, Bernd C. ;
Lincoln, John A. ;
Lubetzki, Catherine ;
Miller, Aaron E. ;
Montalban, Xavier ;
O'Connor, Paul W. ;
Petkau, John ;
Pozzilli, Carlo ;
Rudick, Richard A. ;
Sormani, Maria Pia ;
Stueve, Olaf ;
Waubant, Emmanuelle ;
Polman, Chris H. .
NEUROLOGY, 2014, 83 (03) :278-286
[35]   Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis [J].
Luchetti, Sabina ;
Fransen, Nina L. ;
van Eden, Corbert G. ;
Ramaglia, Valeria ;
Mason, Matthew ;
Huitinga, Inge .
ACTA NEUROPATHOLOGICA, 2018, 135 (04) :511-528
[36]   Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder [J].
Min, Ju-Hong ;
Kim, Byoung Joon ;
Lee, Kwang Ho .
MULTIPLE SCLEROSIS JOURNAL, 2012, 18 (01) :113-115
[37]   ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis [J].
Montalban, X. ;
Gold, R. ;
Thompson, A. J. ;
Otero-Romero, S. ;
Amato, M. P. ;
Chandraratna, D. ;
Clanet, M. ;
Comi, G. ;
Derfuss, T. ;
Fazekas, F. ;
Hartung, H. P. ;
Havrdova, E. ;
Hemmer, B. ;
Kappos, L. ;
Liblau, R. ;
Lubetzki, C. ;
Marcus, E. ;
Miller, D. H. ;
Olsson, T. ;
Pilling, S. ;
Selmaj, K. ;
Siva, A. ;
Sorensen, P. S. ;
Sormani, M. P. ;
Thalheim, C. ;
Wiendl, H. ;
Zipp, F. .
EUROPEAN JOURNAL OF NEUROLOGY, 2018, 25 (02) :215-237
[38]   Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis [J].
Montalban, X. ;
Hauser, S. L. ;
Kappos, L. ;
Arnold, D. L. ;
Bar-Or, A. ;
Comi, G. ;
de Seze, J. ;
Giovannoni, G. ;
Hartung, H. -P. ;
Hemmer, B. ;
Lublin, F. ;
Rammohan, K. W. ;
Selmaj, K. ;
Traboulsee, A. ;
Sauter, A. ;
Masterman, D. ;
Fontoura, P. ;
Belachew, S. ;
Garren, H. ;
Mairon, N. ;
Chin, P. ;
Wolinsky, J. S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (03) :209-220
[39]   Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration [J].
Novgorodov, Alexander S. ;
El-Alwani, Mazen ;
Bielawski, Jacek ;
Obeid, Lina M. ;
Gudz, Tatyana I. .
FASEB JOURNAL, 2007, 21 (07) :1503-1514
[40]   Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator? [J].
Okajima, F .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2002, 1582 (1-3) :132-137