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

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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.

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    Authors and Affiliations

    1. Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX, 75216, USA

      Rehana Hussain, Shirley O’Leary, Ellen Marder & Olaf Stüve

    2. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

      Rehana Hussain, Tresa E. Zacharias, Paul Litvak, Peter Sguigna, Ellen Marder & Olaf Stüve

    3. Spinal Cord Injury Unit, VA North Texas Health Care System, Medical Service, Dallas, TX, USA

      Fides M. Pacheco

    4. Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

      Fides M. Pacheco

    5. Dermatology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA

      Kevin Kia

    6. Department of Dermatology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

      Kevin Kia

    7. Ophthalmology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA

      Karanjit Kooner

    8. Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

      Karanjit Kooner

    9. Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

      Olaf Stüve

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    1. Rehana Hussain
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    2. Shirley O’Leary
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    3. Fides M. Pacheco
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    4. Tresa E. Zacharias
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    5. Paul Litvak
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    7. Ellen Marder
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    9. Karanjit Kooner
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    10. Olaf Stüve
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    Correspondence to Olaf Stüve.

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    Conflicts of interest

    Dr. Olaf Stüve serves on the editorial boards of JAMA Neurology, Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders. Dr. Stüve has served on data monitoring committees for Pfizer and Sanofi-Aventis without monetary compensation. Dr. Stüve collaborated with Medscape on educational initiatives. Dr. Stüve represented Novartis in front of a Scientific Advisory Group at the European Medicines Agency (EMA). Dr. Stüve has advised Genentech and Sanofi-Aventis. Dr. Stüve has consulted for Huron Life Sciences and Navigant Consulting. Dr. Stüve currently receives grant support from Teva Pharmaceuticals and Opexa Therapeutics. Dr. Stüve received travel support from Pfizer. Dr. Stüve is funded by a Merit grant from the US Department of Veterans Affairs.

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    R. Hussain and S. O’Leary contributed equally.

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    Hussain, R., O’Leary, S., Pacheco, F.M. et al. Acute relapse after initiation of Siponimod in a patient with secondary progressive MS. J Neurol 263, 606–610 (2016). https://doi.org/10.1007/s00415-015-7999-6

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    • DOI: https://doi.org/10.1007/s00415-015-7999-6

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