Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

[Structural and functional changes of the hippocampus in patients with multiple sclerosis and their relationship with memory processes]. / Cambios estructurales y funcionales del hipocampo en pacientes con esclerosis múltiple y su relación con procesos de memoria.

INTRODUCTION: One of the most prevalent cognitive deficits in multiple sclerosis (MS) patients relates to (both verbal and visual) information encoding, a process related the hippocampus. AIM: To assess the relationship between information learning and long-term retention processes and hippocampal volume and functional connectivity (FC) in MS patients. SUBJECTS AND METHODS: MS patients and a control group of healthy volunteers were assessed using the brief neuro-psychological battery, which includes tests of verbal and visual memory. Gray matter volume was assessed through the voxel based morphometry technique, and a study of seed-based FC focused on the region of ??interest (hippocampus) was also conducted. RESULTS: Results revealed that, as compared to the control group, MS patients display gray matter atrophy at the left hippocampus gray matter and smaller FC between left hippocampus and brainstem, cerebellum, fusiform gyrus and superior temporal gyrus. Association analyses were performed between memory tests performance and both volumetric and FC changes. Results showed a positive correlation between gray matter hippocampal (bilateral) volume and verbal memory performance of the MS group. Further, in MS patients, a positive correlation between visual memory performance and FC between the left hippocampus and several temporal regions was also found. CONCLUSIONS: The results of the present study reveal a relationship between structural and functional changes in the hippocampus of MS patients and their performance on verbal and visual memory tests.

TITLE: Cambios estructurales y funcionales del hipocampo en pacientes con esclerosis multiple y su relacion con procesos de memoria.Introduccion. Una de las alteraciones cognitivas mas prevalentes en los pacientes con esclerosis multiple son los problemas de codificacion de la informacion (tanto verbal como visual), proceso relacionado con el hipocampo. Objetivo. Estudiar la relacion entre los procesos de aprendizaje y retencion de la informacion a largo plazo con el volumen hipocampal y la conectividad funcional (CF) en pacientes con esclerosis multiple comparados con un grupo control. Sujetos y metodos. Ambos grupos fueron evaluados con la bateria neuropsicologica breve, que incluye pruebas de memoria verbal y visual. Se realizo el estudio de volumetria de la sustancia gris mediante la tecnica de morfometria basada en el voxel y un estudio de CF de voxel de semilla centrado en la zona de interes (hipocampo). Se realizaron analisis de asociacion entre rendimiento en memoria y cambios volumetricos y de CF. Resultados. Los resultados mostraron atrofia en la sustancia gris en el hipocampo izquierdo y una menor CF entre el hipocampo izquierdo y el troncoencefalo, el cerebelo, el giro fusiforme y el giro temporal superior en los pacientes respecto al grupo control. En el grupo de pacientes se observa una correlacion positiva entre la sustancia gris en ambos hipocampos y el rendimiento en memoria verbal, asi como una correlacion positiva entre el rendimiento en memoria visual y la CF entre el hipocampo izquierdo y diversas regiones temporales. Conclusiones. Los resultados muestran una relacion entre el rendimiento de memoria verbal y visual, y cambios estructurales y funcionales en el hipocampo en pacientes con esclerosis multiple.

[Provincial stroke code: characteristics and impact on health care]. / Código ictus provincial: características e impacto asistencial.

INTRODUCTION: Endovenous thrombolysis is the preferred treatment in the early hours following cerebral infarction and delays are the main obstacle preventing it from being used on a more widespread basis. The stroke code (SC) is a system that allows stroke patients to be identified quickly and taken to the most suitable hospital for such treatment to be implemented. AIM. To determine the impact of extending the intra-hospital SC (ISC) to a provincial SC (PSC). PATIENTS AND METHODS: The system consists in a prospective register of cases of SC treated in a provincial stroke centre. Data on the cases of cerebral infarction admitted consecutively the year prior to and after beginning the PSC (1st November 2008) were collected. RESULTS: In one year 318 SC were handled: 61.2% were extra-hospital SC (ESC). A total of 45 patients were thrombolysed: 14.2% of the activations and 25.7% of cerebral infarctions with the code activated. The gross annual rate of thrombolysis was 7.7/100,000 inhabitants (95% confidence interval, 95% CI = 5.7-10.4). Primary medicine activated 34% of the codes. There are no significant differences between ESC and ISC as regards the percentage of correct activations and thrombolysis. The door-to-needle delay is shorter in ESC (59.7 ± 24 versus 74.4 ± 20 minutes; p = 0.012). The time slot from 22 pm to 8 am covers 23.6% of the SC and 22.2% of cases of thrombolysed patients. From the first to the second period, SC activation rises from 11.1% to 37.9% of cerebral infarctions and thrombolysis increases from 3.8 to 12.7% (p < 0.0001; odds ratio = 4.1; 95% CI = 1.9-8.6). CONCLUSIONS: The PSC allowed thrombolysis of cerebral infarction to be carried out in four times as many cases, as well as improving the health care chain and extending it throughout the whole province.