Severe multiple sclerosis relapse under fingolimod therapy: Incident or coincidence?

Abstract

Fingolimod is the first orally administered disease-modifying drug that has been approved for treatment of relapsing-remitting multiple sclerosis (MS). After phosphorylation it acts as a nonselective functional antagonist of the sphingosine-1-phosphate receptor family (S1P1/3/4/5), trapping B and T lymphocytes in secondary lymphoid tissues. ### Case report. A 26-year-old woman was diagnosed with relapsing-remitting MS in February 2009 after an episode of mild sensory deficits. She was treated with interferon β-1a which was stopped in January 2010 due to elevated liver enzymes, and switched to interferon β-1b 2 months later. Despite 7 steroid-responsive relapses her Expanded Disability Status Scale (EDSS) remained stable (1.0 to 1.5) until the end of April 2010 (figure, A and B), when she had her first moderate relapse (EDSS 2.5). Assuming a lack of treatment efficacy, the patient discontinued interferon therapy but refused treatment with natalizumab due to safety concerns. Eventually she was enrolled in an open-label fingolimod trial on June 19, 2010. Figure Disease course, imaging, and laboratory results (A) The patient's disease course: bottom: results of blood immunophenotyping. (B) On May 3, 2010, 6 weeks before initiation of fingolimod therapy, the cerebral MRI (axial T2 and T1+Gd) disclosed several supratentorial and infratentorial multiple sclerosis lesions without gadolinium enhancement. The MRI was obtained immediately after a high-dose IV steroid treatment. (C) MRI at admission in September 2010. Left: the cerebral MRI (axial T2 and T1+Gd) disclosed 29 supratentorial and infratentorial ovoid as well as confluent active lesions, some with ring-like gadolinium enhancement. Moreover, there was a large lesion in the left cerebellar peduncle, without diffusion restriction in diffusion-weighted imaging (not shown). Right: MRI of the cervical and thoracic spinal …