title: Acute relapse after initiation of Siponimod in a patient with secondary progressive MS.
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.
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX, 75216, USA.|Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Rehana
authors.initials: R
authors.lastname: Hussain
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX, 75216, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: O'Leary
authors.affiliation: Spinal Cord Injury Unit, VA North Texas Health Care System, Medical Service, Dallas, TX, USA.|Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Fides M
authors.initials: FM
authors.lastname: Pacheco
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Tresa E
authors.initials: TE
authors.lastname: Zacharias
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Litvak
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sguigna
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX, 75216, USA.|Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Marder
authors.affiliation: Dermatology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA.|Department of Dermatology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kia
authors.affiliation: Ophthalmology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA.|Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Karanjit
authors.initials: K
authors.lastname: Kooner
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX, 75216, USA. olaf.stuve@utsouthwestern.edu.|Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. olaf.stuve@utsouthwestern.edu.|Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. olaf.stuve@utsouthwestern.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D000328:Adult; D001384:Azetidines / Q000009:adverse effects*; D001593:Benzyl Compounds / Q000009:adverse effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012008:Recurrence; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000139:chemically induced / Q000473:pathology
chemical_list: D001384:Azetidines; D001593:Benzyl Compounds; C578989:siponimod
keywords: Lymphocytes; Multiple sclerosis; Pharmacotherapy; Relapse; Siponomid; Sphingosine 1-phosphate; Therapy