Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Relapse recovery in relapsing-remitting multiple sclerosis: An analysis of the CombiRx dataset.

BACKGROUND: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery. OBJECTIVE: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS). METHODS: Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to unconfirmed and confirmed relapse recovery. RESULTS: CombiRx included 1008 participants. We investigated 240 relapses. Median time to relapse recovery was 111 days. Most recovery events took place within 1 year of relapse onset: 202 of 240 (84%) individuals recovered during follow-up, 161 of 202 (80%) by 180 days, and 189 of 202 (94%) by 365 days. Relapse severity was the only factor associated with relapse recovery. CONCLUSION: Recovery from relapses takes place up to approximately 1 year after the event. Relapse severity, but no other patient factors, was associated with the speed of relapse recovery. Our findings inform clinical practice and trial design in RRMS.

Disease modifying therapy switching in relapsing multiple sclerosis: A Delphi consensus of the demyelinating expert group of the Spanish society of neurology.

BACKGROUND: The increase in available disease modifying therapies (DMTs) for multiple sclerosis has led to greater emphasis on improving treatment sequencing paradigms. This article summarises the opinions from a panel of 25 experts on treatment switching approaches in relapsing multiple sclerosis (RMS). METHODS: A modified Delphi consensus process was carried out to develop clinically relevant statements for aiding treatment decisions in patients with RMS between the 16th January and the 9th October 2019. A sub-group of two experts (core group) carried out an extensive review of the literature and formulated 106 statements for the expert panel to evaluate. RESULTS: From a total number of 106 statements that were submitted to the expert panel for critical evaluation, consensus (at least 80% of the panelists agreed) was reached on 99 of them. These statements cover treatment objectives, reasons for DMT switching, suboptimal response criteria, strategies for treatment change and washout periods. CONCLUSION: The agreed statements provide up-to-date guidance on DMT sequencing for optimal patient management.

Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab.

Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4wks or extended interval dose (EID) of 300 mg/6wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual's dosing schedule.

¿Va a cambiar la neurología tras la pandemia de Covid-19 en los próximos cinco años?. Estudio de enfoque mediante informadores clave / Will neurological care change over the next 5 years due to the COVID-19 pandemic?

INTRODUCCIÓN: La pandemia de Covid-19 va a conllevar cambios en la asistencia neurológica, que no se pueden prever fácilmente a largo plazo. MATERIAL Y MÉTODOS: A través de un modelo de informadores clave, se busca el consenso siendo los encuestados, jefes de servicio de Neurología con conocimiento amplio de la situación al haber actuado durante la pandemia, de cómo va a ser la especialidad en un plazo de cinco años. RESULTADOS: Aunque se obtiene un grado de acuerdo bajo entre encuestados, si se describen acuerdos por consenso a nivel mayor (85%) y menor (70%). Los principales acuerdos se refieren al incremento de precauciones, al uso de la telemedicina, al mantenimiento de las consultas telefónicas, a la reducción de asistencia a las consultas evitando que hayan salas de espera con un número alto de personas, al desarrollo de técnicas docentes no presenciales y a la adaptación en el desarrollo de ensayos clínicos en relación a la visita de los monitores. Sin embargo, no se acuerda que haya cambios en la indicación de exploraciones complementarias, ni en la propia exploración neurológica. CONCLUSIÓN: El método de informadores clave ha permitido conocer que cambios se pueden prever tras la pandemia

INTRODUCTION: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. MATERIAL AND METHODS: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. RESULTS: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. CONCLUSION: The key informant survey identified the foreseeable changes in neurological care after the pandemic

Psychometric properties of the SDM-Q-9 questionnaire for shared decision-making in multiple sclerosis: item response theory modelling and confirmatory factor analysis.

BACKGROUND: Shared decision-making is a cornerstone of patient-centred care. The 9-item Shared Decision-Making Questionnaire (SDM-Q-9) is a brief self-assessment tool for measuring patients' perceived level of involvement in decision-making related to their own treatment and care. Information related to the psychometric properties of the SDM-Q-9 for multiple sclerosis (MS) patients is limited. The objective of this study was to assess the performance of the items composing the SDM-Q-9 and its dimensional structure in patients with relapsing-remitting MS. METHODS: A non-interventional, cross-sectional study in adult patients with relapsing-remitting MS was conducted in 17 MS units throughout Spain. A nonparametric item response theory (IRT) analysis was used to assess the latent construct and dimensional structure underlying the observed responses. A parametric IRT model, General Partial Credit Model, was fitted to obtain estimates of the relationship between the latent construct and item characteristics. The unidimensionality of the SDM-Q-9 instrument was assessed by confirmatory factor analysis. RESULTS: A total of 221 patients were studied (mean age = 42.1 ± 9.9 years, 68.3% female). Median Expanded Disability Status Scale score was 2.5 ± 1.5. Most patients reported taking part in each step of the decision-making process. Internal reliability of the instrument was high (Cronbach's α = 0.91) and the overall scale scalability score was 0.57, indicative of a strong scale. All items, except for the item 1, showed scalability indices higher than 0.30. Four items (items 6 through to 9) conveyed more than half of the SDM-Q-9 overall information (67.3%). The SDM-Q-9 was a good fit for a unidimensional latent structure (comparative fit index = 0.98, root-mean-square error of approximation = 0.07). All freely estimated parameters were statistically significant (P < 0.001). All items presented standardized parameter estimates with salient loadings (>0.40) with the exception of item 1 which presented the lowest loading (0.26). Items 6 through to 8 were the most relevant items for shared decision-making. CONCLUSIONS: The SDM-Q-9 presents appropriate psychometric properties and is therefore useful for assessing different aspects of shared decision-making in patients with multiple sclerosis.

Country break-out session highlights.

Individuals with multiple sclerosis (MS) spasticity present a wide range of symptoms and disability levels that are frequently challenging to manage. At the MS Experts Summit 2015, five country breakout sessions were conducted in parallel, and mainly in the native language, to examine various aspects about the management of treatment-resistant MS spasticity. Topics covered included video documentation of MS spasticity management (Germany), use of cannabinoid medicines in daily practice (Italy), multidisciplinary approach to MS spasticity care (France), titration and adherence to treatments for MS spasticity (Spain) and management of MS symptoms (Norway/Rest of World). For the benefit of all attendees, session highlights were collated and presented in a Plenary Session which is summarized herein.

Apolipoprotein alleles and the response to interferon-ß-1b in multiple sclerosis.

BACKGROUND: Results for the e4/e2 alleles of the ApoE gene as markers of susceptibility, clinical and radiological progression, and cognitive deterioration in patients with multiple sclerosis (MS) are contradictory. AIM: The usefulness of these markers in predicting the response to interferon-ß-1b (IFNß-1b) was evaluated. MATERIAL AND METHODS: 95 patients with relapsing-remitting MS treated with IFNß-1b (mean follow-up 7.44 years) were studied. We correlated the e4 and e2 alleles with the time to the first relapse or to a 1-point worsening on the Expanded Disability Status Scale, time to moderate disability, progression index, and treatment discontinuation due to inefficacy. RESULTS: We found no association between the e4 allele and any of the variables. The e2 allele was associated with increased time to moderate disability. CONCLUSION: The e4 allele of ApoE has no prognostic value for the response to IFNß-1b. The e2 allele delayed the progression of disability in our MS patient cohort.

Interferon-beta1b in multiple sclerosis: effect on progression of disability and clinical markers of treatment response.

There is limited long-term data on the effect of interferon-beta1b (IFN-beta1b) on disability progression in patients with multiple sclerosis (MS). There is also no reliable way of predicting individual responses to IFN-beta1b treatment. This prospective study investigated early clinical prognostic markers of disease activity and progression in 115 patients with relapsing-remitting MS (RRMS) treated with IFN-beta1b for almost 5 years. The study also compared progression of disability in IFN-beta1b-treated patients with a historic untreated cohort of MS patients (n = 44). The number of relapses in the first 2 years of MS and in the 2 years before treatment predicted an early relapse after IFN-beta1b treatment. The IFN-beta1b-treated group experienced a slower progression of disability than the untreated cohort, suggesting that IFN-beta1b treatment delays progression of disability in RRMS.