Acute relapse after initiation of Siponimod in a patient with secondary progressive MS

Rehana Hussain, Shirley O’Leary, Fides M. Pacheco, Tresa E. Zacharias, Paul Litvak, Peter Sguigna, Ellen Marder, Kevin Kia, Karanjit Kooner, Olaf Stüve

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sphingosine 1-phosphate (S1P) is a signaling molecule that binds to five G protein-coupled receptors (Proc Natl Acad Sci USA 108:751–756, 2011). Modulation of these receptors has been associated with pleiotropic biological effects in the immune, cardiovascular, and central nervous systems (CNS). The functional S1P receptor antagonist fingolimod was the first member of this class of pharmacotherapeutics to be approved for treatment of relapsing multiple sclerosis (MS). Siponimod is currently in clinical trial in patients with secondary progressive (SP) MS, a clinical trial for which there is an unmet need for disease-modifying agents. 10 weeks into the trial, the patient awoke with blurry vision in his left eye, and was subsequently diagnosed with an acute optic neuritis. Despite discontinuation of siponimod and treatment with pulse corticosteroids, the patient did not regain visual function in the affected eye. This is the first report of disease reactivation shortly after initiating siponimod in a patient with SPMS. This case illustrates that the known changes in lymphocyte numbers and composition in the CNS associated with S1P receptor antagonism during the SPMS disease stage may have adverse outcomes in some patients during treatment initiation, and that close clinical and paraclinical monitoring is advised.

Original languageEnglish (US)
Pages (from-to)606-610
Number of pages5
JournalJournal of Neurology
Volume263
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Chronic Progressive Multiple Sclerosis
Recurrence
Lysosphingolipid Receptors
Central Nervous System
Clinical Trials
Optic Neuritis
Lymphocyte Count
G-Protein-Coupled Receptors
Multiple Sclerosis
Adrenal Cortex Hormones
Therapeutics
1-(4-(1-((E)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino)-ethyl)-2-ethylbenzyl)-azetidine-3-carboxylic acid

Keywords

  • Lymphocytes
  • Multiple sclerosis
  • Pharmacotherapy
  • Relapse
  • Siponomid
  • Sphingosine1-phosphate
  • Therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Acute relapse after initiation of Siponimod in a patient with secondary progressive MS. / Hussain, Rehana; O’Leary, Shirley; Pacheco, Fides M.; Zacharias, Tresa E.; Litvak, Paul; Sguigna, Peter; Marder, Ellen; Kia, Kevin; Kooner, Karanjit; Stüve, Olaf.

In: Journal of Neurology, Vol. 263, No. 3, 01.03.2016, p. 606-610.

Research output: Contribution to journalArticle

Hussain, Rehana ; O’Leary, Shirley ; Pacheco, Fides M. ; Zacharias, Tresa E. ; Litvak, Paul ; Sguigna, Peter ; Marder, Ellen ; Kia, Kevin ; Kooner, Karanjit ; Stüve, Olaf. / Acute relapse after initiation of Siponimod in a patient with secondary progressive MS. In: Journal of Neurology. 2016 ; Vol. 263, No. 3. pp. 606-610.
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