Varicella zoster virus and influenza vaccine antibody titres in patients from MAGNIFY-MS who were treated with cladribine tablets for highly active relapsing multiple sclerosis

Lette

Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study

Alemtuzumab; Disease-modifying therapy; Multiple sclerosisAlemtuzumab; Teràpia modificadora de la malaltia; Esclerosi múltipleAlemtuzumab; Terapia modificadora de la enfermedad; Esclerosis múltipleBackground and objectives: Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants (‘alemtuzumab-only’) could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab (‘IFN-alemtuzumab’). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5–7 years (11–13 years after alemtuzumab/IFN initiation). Methods: Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening [CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0], and 6-month confirmed disease improvement [CDI; >1.0-point EDSS decrease (baseline score ⩾2.0)]. Results: 43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3–13 for the alemtuzumab-only [0.17; 95% confidence interval (CI) 0.15–0.20] and IFN-alemtuzumab (0.14; 0.11–0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent. Conclusion: Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11–13 years, and most participants did not require more than one additional course.The TOPAZ study as well as writing and editorial support for this article were funded by Sanofi

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Esclerosis múltiple; Reacciones adversas; Infecciones respiratoriasEsclerosi múltiple; Reaccions adverses; Infeccions respiratòriesMultiple sclerosis; Adverse reactions; Respiratory infectionsObjective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.The study was funded by the Academia Española de Esclerosis Múltiple y Otras Enfermedades Autoinmunes (ACADEM), with a restricted investigational grant form Novartis. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Revisión sistemática sobre la eficacia y seguridad de los neuroestimuladores periféricos del ganglio esfenopalatino para el tratamiento de la cefalea crónica en racimos refractaria

[EN] Introduction: This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache. Development: Various medical databases were used to perform a systematic review of the scientific literature. The search for articles continued until 31 October 2016, and included clinical trials, systematic reviews and/or meta-analyses, health technology assessment reports, and clinical practice guidelines that included measurements of efficiency/effectiveness or adverse effects associated with the treatment. The review excluded cohort studies, case–control studies, case series, literature reviews, letters to the editor, opinion pieces, editorials, and studies that had been duplicated or outdated by later publications from the same institution. Regarding effectiveness, we found that SPG stimulation had positive results for pain relief, attack frequency, medication use, and patients’ quality of life. In the results regarding safety, we found a significant number of adverse events in the first 30 days following the intervention. Removal of the device was necessary in some patients. Little follow-up data, and no long-term data, is available. Conclusions: These results are promising, despite the limited evidence available. We consider it essential for research to continue into the safety and efficacy of SPG stimulation for patients with refractory chronic cluster headache. In cases where this intervention may be indicated, treatment should be closely monitored. [ES] Introducción: El objetivo es evaluar la eficacia y seguridad de los neuroestimuladores periféricos del ganglio esfenopalatino (GEP) para el tratamiento de la cefalea en racimos crónica refractaria al tratamiento. Desarrollo: Revisión sistemática de la literatura científica. Se identificaron estudios mediante una búsqueda en diferentes bases de datos. Las estrategias de búsqueda se realizaron hasta el 31 de octubre de 2016, incluyendo ensayos clínicos, revisiones sistemáticas o metaanálisis, informes de evaluación de tecnologías sanitarias y guías de práctica clínica que recogieran medidas de eficacia/efectividad o efectos adversos asociados al tratamiento. Se excluyeron estudios de cohortes, casos y controles, series de casos, revisiones narrativas, cartas al director, artículos de opinión, editoriales y estudios duplicados o desfasados por estudios posteriores de la misma institución. Respecto a la eficacia, los resultados son positivos tras la estimulación del GEP en relación con el alivio de dolor, el número de episodios, el uso de la medicación o la calidad de vida del paciente. En relación con la seguridad, hay un número importante de efectos adversos en los primeros 30 días de la intervención y en algunos pacientes fue necesaria la retirada del dispositivo. Los datos de seguimiento son a corto plazo y escasos. Conclusiones: Los resultados resultan prometedores a pesar de que la evidencia disponible es limitada. Consideramos fundamental continuar con la investigación sobre la seguridad y eficacia de los neuroestimuladores del GEP en la cefalea en racimos crónica. En aquellos casos en que pueda estar indicada la intervención, el tratamiento debería realizarse supervisado en un estudio de monitorización.S

ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs

Background: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. / Objective: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). / Methods: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk–benefit balance. / Results: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. / Conclusion: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS

Prolonged-release fampridine in multiple sclerosis: clinical data and real-world experience – report of an expert meeting

Prolonged-release (PR) fampridine is the only approved medication to improve walking in multiple sclerosis (MS), having been shown to produce a clinically meaningful improvement in walking ability in the subset of MS patients with Expanded Disability Status Scale 4-7. Recent responder subgroup analyses in the phase III ENHANCE study show a large effect size in terms of an increase of 20.58 points on the patient-reported 12-item MS Walking Scale in the 43% of patients classified as responders to PR-fampridine, corresponding to a standardized response mean of 1.68. Use of PR-fampridine in clinical practice varies across Europe, depending partly on whether it is reimbursed. A group of European MS experts met in June 2017 to discuss their experience with using PR-fampridine, including their views on the patient population for treatment, assessment of treatment response, re-testing and re-treatment, and stopping criteria. This article summarizes the experts' opinions on how PR-fampridine can be used in real-world clinical practice to optimize the benefits to people with MS with impaired walking ability.info:eu-repo/semantics/publishedVersio

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod : The Spanish GILENYA registry

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continuedto be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance

Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome : A MAGNIMS multicentre study

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research has been supported by a programme grant (14-358e) from the Dutch MS Research Foundation (Voorschoten, The Netherlands). The study in London was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.Background: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain. Objectives: The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis. Methods: We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3-6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010). Results: In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T (p = 0.005). For patients, this was 4.18 and 4.40, respectively (p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters. Conclusion: Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training

Single-subject structural cortical networks in clinically isolated syndrome

BACKGROUND: Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas, and they present the advantage of being extracted from previously acquired clinical magnetic resonance imaging (MRI) scans. SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis. OBJECTIVE: To investigate alterations of SCNs at the individual level in patients with clinically isolated syndrome (CIS), thereby assessing their clinical relevance. METHODS: We analyzed baseline data collected in a prospective multicenter (MAGNIMS) study. CIS patients (n = 60) and healthy controls (n = 38) underwent high-resolution 3T MRI. Measures of disability and cognitive processing were obtained for patients. Single-subject SCNs were extracted from brain 3D-T1 weighted sequences; global and local network parameters were computed. RESULTS: Compared to healthy controls, CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed. Alterations of centrality measures and clustering of connections were observed in specific cortical areas in CIS patients when compared with healthy controls. CONCLUSION: Our study indicates that SCNs can be used to demonstrate clinically relevant alterations of connectivity in CIS