Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response.

Background: Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler's murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection in vitro. Objective: 1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide. Methods: A total of 101 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 80 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L). Results: Antiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3. Conclusion: Treatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response.

Fingolimod Use for the Treatment of Multiple Sclerosis in a Clinical Practice Setting in Madrid.

OBJECTIVE: To assess the effectiveness and safety of fingolimod use in a Spanish clinical practice setting. METHODS: Retrospective study with multiple sclerosis patients who received at least 1 fingolimod dose between January 2004 and January 2015. Effectiveness and safety data were collected during the entire treatment of each patient. Analysis was performed for the total population and stratified according to prior treatment, sex, and age at treatment initiation. RESULTS: A total of 167 patients were included, 50.9% had prior immunomodulator use, 33.5% natalizumab use, and 15.6% were naive patients. The annual relapse rate (ARR) decreased for the total population at month 12 (62%) and month 24 (84%) (P < 0.0001, in both cases); for naive patients (P < 0.05) and patients with prior immunomodulator use (P < 0.0001); for patients with prior natalizumab use, the ARR kept low after treatment initiation (0.23). After 24 months, the proportion of relapse-free patients was 70% or greater and disability progression-free patients was 80% or greater. No significant differences were observed when the results were compared by prior treatment, sex, or age. Thirty-two patients (19.2%) reported adverse drug reactions and 9.6% discontinued: 4.8% due to adverse drug reactions and 4.8% for lack of effectiveness. CONCLUSIONS: The results support fingolimod use due to clinical effectiveness, tolerability, and ease of administration.

[Monoclonal antibodies for the treatment of multiple sclerosis]. / Anticuerpos monoclonales para el tratamiento de la esclerosis múltiple.

Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs.

Dural cavernous haemangioma of the anterior cranial fossa.

Extra-axial cavernous haem angiomas are uncommon lesions histologically identical to cavernomas in other locations. However, their radiological features and clinical behaviour may differ. They are frequently misdiagnosed preoperatively, as they often mimic other tumours. We describe a patient suffering from loss of the sense of smell, due to a cavernous haemangioma implanted in the dura mater of the anterior cranial fossa close to the olfactory bulb. To our knowledge, this is the first patient reported with such a lesion.