Kaplan–Meier estimates for the time to confirmed disability progression according to prior treatment.

<p>N, number; NR, not reached; IM, immunomodulator; NTZ, Natalizumab; 95%CI, 95% confidence interval.</p

Adverse events (AEs) during fingolimod treatment.

<p>Adverse events (AEs) during fingolimod treatment.</p

Kaplan–Meier estimates for the time to a first confirmed relapse according to EDSS score.

<p>N, number; NR, not reached.</p

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

<div><p>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.</p><p>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.</p><p>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.</p><p>The real-world fingolimod benefits observed in this study seem to be similar than those observed in previous clinical trials.</p></div

Annualized relapse rate in the 24 months prior to fingolimod treatment and the first 24 months of fingolimod for total cohort and stratified according to prior treatment, sex, age at the fingolimod treatment initiation and number of prior treatments.

<p>* p<0.0001; ** p<0.01; *** p<0.05. EDSS, Expanded Disability Status Scale, FTY, fingolimod, IM, immunomodulator; NTZ, natalizumab; Tx, treatment.</p

Additional file 1: of Cross-cultural adaptation and validation of the VISA-A questionnaire for Chilean Spanish-speaking patients

VISA-A-CH. (DOCX 227 kb

Grand average ERPs for both sessions in nine selected electrodes.

<p>The X axis represents “time” expressed in milliseconds (ms) and the Y axis the “amplitude” of the ERP in microvolts (µV). The vertical dashed line indicates the onset of the stimulus. The black trace is for session 1 and the red trace for session 2. Note the increase in the P3 amplitude especially in centro-parietal derivations.</p

P3 component modulations at Pz electrode and topographic maps.

<p>P3 component modulations at Pz electrode and topographic maps.</p

Experimental procedure.

<p>The possible combinations for sets of cues and targets were six: No cue congruent (NC-C), No cue incongruent (NC-I), Central cue congruent (CC-C), Central cue incongruent (CC-I), Spatial cue congruent (SC-C) and Spatial cue incongruent (SC-I).</p

Contingent Negative Variation modulations at Cz electrode and topographic maps.

<p>Contingent Negative Variation modulations at Cz electrode and topographic maps.</p