Rebound after discontinuation of teriflunomide in patients with multiple sclerosis: 2 case reports.

Teriflunomide is an oral first-line disease modifying treatment (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS). It can take up to two years to achieve systemic clearance of teriflunomide to an acceptable level, but this washout period may be accelerated by administration of cholestyramine. Relapse of multiple sclerosis (MS) during washout of teriflunomide or other first-line DMT is not as common. We report two patients with RRMS who experienced a relapse after the accelerated elimination period (AEP) of teriflunomide and confirmation of negative plasmatic levels (<0.02 µg/ml). In cases of risk of MS activity, we should not wait for teriflunomide negative plasmatic levels confirmation before starting the next DMT to reduce the risk of relapse.

Altered individual behavioral and EEG parameters are related to the EDSS score in relapsing-remitting multiple sclerosis patients.

Functional neuroanatomy of cognitive impairment in multiple sclerosis is currently still a challenge. During the progression of the disease, several cognitive mechanisms deteriorate thus diminishing the patient's quality of life. A primary objective in the cognitive assessment of multiple sclerosis (MS) patients is to find reliable measures utilizing diverse neuroimaging techniques. Moreover, especially relevant in the clinical environment is finding technical approaches that could be applied to individual participants and not only for group analysis. A 64-channel electroencephalographic recording (EEG) was made with thirty participants divided into three groups of equivalent size (N = 10) (healthy control, low-EDSS (1-2.5) and moderate-EDSS (4-6)). Correlation analysis was applied to multiple measures: behavior, neuropsychological tests (Paced Auditory Serial Addition Test, 3 seconds (PASAT-3s) and the Symbol Digit Modality Test (SDMT)), Expanded Disability Status Scale (EDSS), even-related potential (P3) and event-related desynchronization (ERD) parameters and the correlation scores between individual participant's P3/ERD maps and the healthy grand average P3/ERDmaps. Statistical analysis showed that diverse parameters exhibited significant correlations. A remarkable correlation was the moderate score found between SDMT and EDSS (r = -0.679, p = 0.0009). However, the strongest correlation was between the value of integrated measures (reaction time, P3 and ERD latency) and EDSS (r = 0.699, p = 0.0006). In regard to correlations for grand average maps between groups, the P3 component exhibited a lower score according to a more deteriorated condition (higher EDSS). In contrast, ERD maps remained stable with an increase of EDSS. Lastly, a Z-transformation of individual values of all variables included in the study exhibited heterogeneity in cognitive alterations in the multiple sclerosis participants.

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

BACKGROUND: Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. PATIENTS AND METHODS: In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. RESULTS: Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. CONCLUSION: Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: An observational study.

Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments. A multivariante model was used to assess the ARR with baseline characteristics. The safety profile (adverse events [AEs]) was also described. Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the total cohort, patients previously treated with immunomodulatory and naïve patients (p<0.0001 all cases). However, patients previously treated with natalizumab kept a constant ARR. The ARR results and the consequent increase in the proportion of relapse-free patients were independent of the age at treatment initiation, number of prior treatments, gender and basal Gd+ lesions. Although fingolimod was effective regardless the basal EDSS score and ARR prior to fingolimod treatment, better outcomes were observed in patients with basal EDSS score <3 (0.2 vs. 0.4; p = 0.0244) and ARR ≥ 2 prior to fingolimod treatment (p = 0.0338). Only the basal EDSS score was association with ARR in the first 24 months of fingolimod treatment in the multivariante model (p = 0.0439). The cumulative probability of disability progression was 20% (month-24) in the total cohort, and was independent from prior treatment, age at treatment initiation, number of prior treatments, gender, basal EDSS score, basal Gd+ lesions and ARR prior to treatment. The real-world fingolimod benefits observed in this study seem to be similar than those observed in previous clinical trials.