Occurrence of area postrema syndrome during follow-up: phenotype and influence over NMOSD activity in LATAM in real-world settings.

INTRODUCTION: We aimed to assess the frequency, duration, and severity of area postrema syndrome (APS) during follow-up in neuromyelitis optica spectrum disorder (NMOSD) patients, as well as its association with inflammatory activity and prognostic factors of APS severity in a real-world setting. METHODS: We conducted a retrospective study on a cohort of Latin American (LATAM) NMOSD patients who had experienced APS during their follow-up. Patients from Mexico, Peru, Brazil, Colombia, Panama, Chile and Argentina patients who met 2015 NMOSD criteria were included. We evaluated data on symptom type (nausea, vomiting and/or hiccups), frequency, duration, severity (measured by APS severity scale), association with other NMOSD core relapses, and acute treatments (symptomatic and immunotherapy or plasmapheresis). Logistic regression was conducted to evaluate factors associated with APS severity (vs. mild-moderate). RESULTS: Out of 631 NMOSD patients, 116 (18.3%) developed APS during their follow-up. The most common APS phenotype was severe. Inflammatory activity (i.e., relapses) significantly decreased after the onset of APS. Half of the patients experienced isolated APS with a median duration of 10 days, and the most frequently used acute treatment was IV steroids. All three symptoms were present in 44.6% of the patients. APS symptoms resolved following immunotherapy. Logistic regression did not identify independent factors associated with the severity of APS. CONCLUSIONS: Our findings indicate that 18.3% of NMOSD patients developed APS during the follow-up period, with most patients fulfilling criteria for severe APS. The inflammatory activity decreased after the onset of APS compared to the previous year.

Burden of treatment and quality of life in relapsing remitting multiple sclerosis patients under early high efficacy therapy in Argentina: Data from the Argentinean registry.

The objective of this study was to describe and compare the burden of treatment (BOT) and the quality of life (QoL) in early high efficacy therapy (HET) vs. escalation therapy in relapsing remitting multiple sclerosis (RRMS) patients included in RelevarEM, the Argentinean registry of MS (RelevarEM, NCT 03,375,177). METHODS: cross sectional study conducted between September and December 2022. Participating patients were adults, RRMS patients who initiated (during the last three years) their treatment with a HET (natalizumab, ocrelizumab, alemtuzumab, cladribine) or with escalation treatment (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate or fingolimod). Clinical and demographic aspect were collected. QoL and BOT was measured with the validated to Spanish MusiQol and BOT questionnaire. Propensity score (PS)-based nearest-neighbor matching was applied to homogenize groups. Comparisons were be done using a linear regression analysis model stratified by matched pairs, with BOT and QoL assessments as main outcomes. RESULTS: 269 patients were included in the analysis, mean age 33.7 ± 5.7 years, 193 (71.7 %) were female. A total of 136 patients were on early HET while 133 were on escalation therapy. In the entire group the mean total BOT score (±SD) was 48.5 ± 15.3 while in the group of patients receiving early HET we observed that the mean BOT score (±SD) was 43.5 ± 12.2 vs. 54.3 ± 13.3 in escalation treatment (p < 0.0001). Regarding the score QoL (±SD), in the entire sample we observed a global score of 77.4 ± 11.2. When we stratified groups, in HET (±SD) it was 81.3 ± 14 vs. 74.1 ± 18.3 in escalation therapy (p = 0.0003). CONCLUSION: in this multicenter study that included 269 patients from Argentina we observed in early HET a significantly lower BOT and higher QoL than patients receiving escalation therapy.

Clinical impact of gender and age at onset on disease trajectory in primary progressive multiple sclerosis patients.

BACKGROUND AND OBJECTIVES: Primary-progressive multiple sclerosis (PPMS) is characterized by gradual neurological deterioration without relapses. This study aimed to investigate the clinical impact of gender and age at disease onset on disease progression and disability accumulation in patients with this disease phenotype. METHODS: Secondary data from the RelevarEM registry, a longitudinal database in Argentina, were analyzed. The cohort comprised patients with PPMS who met inclusion criteria. Statistical analysis with multilevel Bayesian robust regression modeling was conducted to assess the associations between gender, age at onset, and Expanded Disability Status Scale (EDSS) score trajectories. RESULTS: We identified 125 patients with a confirmed diagnosis of PPMS encompassing a total of 464 observations. We found no significant differences in EDSS scores after 10 years of disease progression between genders (-0.08; credible interval (CI): -0.60, 0.42). A 20-year difference in age at onset did not show significant differences in EDSS score after 10 years of disease progression (0.281; CI: -0.251, 0.814). Finally, we also did not find any clinically relevant difference between gender EDSS score with a difference of 20 years in age at onset (-0.021; CI: -0.371, 0.319). CONCLUSION: Biological plausibility of gender and age effects does not correlate with clinical impact measured by EDSS score.

Incidence of SARS-CoV-2 infection in patients with multiple sclerosis who received SARS-CoV-2 vaccines and are under treatment with high-efficacy therapies in Argentina.

We aimed to evaluate the incidence of SARS-CoV-2 breakthrough infection of SARS-CoV-2 vaccines in people with MS (PwMS) on high-efficacy disease-modifying therapies (HET) included in the national MS registry in Argentina (RelevarEM). METHODS: Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI). RESULTS: Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period. CONCLUSIONS: We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina.

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: A study from the RelevarEM registry.

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients.

Evaluation of the use of high-efficacy treatments (HETs) in patients with relapsing-remitting multiple sclerosis in Argentina.

BACKGROUND: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years. METHODS: A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included. RESULTS: Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0-1 year) and in treatment-experienced patients it was 5 years (IQR: 3-9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2. CONCLUSION: The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS.

Serological response to SARS-COV-2 vaccines in patients with multiple sclerosis in Argentina / Respuesta serológica a vacunas contra SARS-CoV-2 en pacientes con esclerosis múltiple en Argentina

Abstract Introduction : The objective was to assess the im munogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. Methods : A prospective cohort study between May and December 2021. The primary outcome was im munogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evalua ted based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. Results : 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting mul tiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immu nological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed anti bodies against spike antigen among those that were on ocrelizumab compared to other groups (p ≤ 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diag nosed with COVID-19. Conclusion: We found that MS patients that recei ved Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Resumen Introducción : El objetivo fue evaluar la inmunogeni cidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT 03375177). Métodos : Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detec ción de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la defi nición del Ministerio de Salud. Resultados : Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remiten te-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pa cientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas he terólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p ≤ 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión : Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Frequency of new asymptomatic MRI lesions during attacks and follow-up of patients with NMOSD in a real-world setting.

BACKGROUND: We aimed to assess the frequency of new asymptomatic lesions on brain and spinal imaging (magnetic resonance imaging (MRI)) and their association with subsequent relapses in a large cohort of neuromyelitis optica spectrum disorder (NMOSD) patients in Argentina. METHODS: We retrospectively reviewed 675 MRI (225 performed during an attack and 450 during the relapse-free period (performed at least 3 months from the last attack)) of NMOSD patients who had at least 2 years of clinical and MRI follow-up since disease onset. Kaplan-Meier (KM) curves were used for depicting time from remission MRI to subsequent relapse. RESULTS: We included 135 NMOSD patients (64.4% were aquaporin-4-immunoglobulin G (AQP4-IgG)-positive). We found that 26 (19.26%) and 66 (48.88%) of patients experienced at least one new asymptomatic MRI lesion during both the relapse-free period and attacks, respectively. The most frequent asymptomatic MRI lesions were optic nerves followed by short-segment myelitis during the relapse-free period and attacks. KM curves did not show differences in the time taken to develop a new relapse. CONCLUSION: Our findings showed that new asymptomatic lesions are relatively frequent. However, the presence of new asymptomatic MRI lesions during the relapse-free period and at relapses was not associated with a shorter time to developing subsequent relapses.

Serological response to SARS-CoV-2 vaccines in patients with multiple sclerosis in Argentina.

INTRODUCTION: The objective was to assess the immunogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. METHODS: A prospective cohort study between May and December 2021. The primary outcome was immunogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evaluated based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. RESULTS: 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting multiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immunological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed antibodies against spike antigen among those that were on ocrelizumab compared to other groups (p = 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diagnosed with COVID-19. CONCLUSION: We found that MS patients that received Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Introducción: El objetivo fue evaluar la inmunogenicidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT03375177). Métodos: Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detección de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la definición del Ministerio de Salud. Resultados: Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remitente-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pacientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas heterólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p = 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión: Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Clinical outcomes and prognostic factors in patients with optic neuritis related to NMOSD and MOGAD in distinct ethnic groups from Latin America.

BACKGROUND: Optic neuritis (ON) can be an initial manifestation of neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin 4-antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD). Additionally, both diseases may have overlapping paraclinical and radiological features. These diseases may have different outcomes and prognoses. We aimed to compare clinical outcomes and prognostic features of patients with NMOSD and MOGAD presenting ON as first attack, from different ethnic groups in Latin America. METHODS: We conducted a retrospective observational multicenter study in patients from Argentina (n = 61), Chile (n = 18), Ecuador (n = 27), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 49) with MOGAD or NMOSD related ON. Predictors of disability outcomes at last follow-up, namely visual disability (Visual Functional System Score ≥4), motor disability (permanent inability to walk further than 100 m unaided) and wheelchair dependence based on EDSS score were evaluated. RESULTS: After a mean disease duration of 42.7 (±40.2) months in NMOSD and 19.7 (±23.6) in MOGAD, 55% and 22% (p>0.001) experienced permanent severe visual disability (visual acuity from 20/100 to 20/200), 22% and 6% (p = 0.01) permanent motor disability and 11% and 0% (p = 0.04) had become wheelchair dependent, respectively. Older age at disease onset was a predictor of severe visual disability (OR=1,03 CI95%1.01-1.05, p = 0.03); older age at disease onset (OR=1,04 CI95%1.01-1.07, p = 0.01), higher number of relapses (OR=1,32 CI95%1.02-1.71, p = 0.03) and rituximab treatment (OR=0,36 CI95%0.14-0.90, p = 0.02) were predictors of permanent motor disability, whereas ON associated with myelitis at disease onset was a predictor of wheelchair dependency (OR=4,16, CI95%1.23-14.08, p = 0,02) in NMOSD patients. No differences were found when evaluating distinct ethnic groups (Mixed vs. Caucasian vs. Afro-descendant) CONCLUSIONS: NMOSD was associated with poorer clinical outcomes than MOGAD. Ethnicity was not associated with prognostic factors. Distinct predictors of permanent visual and motor disability and wheelchair dependency in NMOSD patients were found.

Therapeutic strategies in NMOSD and MOGAD patients: A multicenter cohort study in Latin America.

PURPOSE: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. METHODS: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. RESULTS: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60). CONCLUSION: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Neuromyelitis optica spectrum disorders with and without associated autoimmune diseases.

OBJECTIVES: We aimed to determinate the frequency of this association and compare the features of neuromyelitis optica spectrum disorder (NMOSD) with and without associated autoimmune diseases (AD) in a Latin American (LATAM) population in clinical practice. METHODS: We retrospectively reviewed the medical records of patients with NMOSD according to the 2015 diagnostic criteria. Patients from Argentina (n=77), Brazil (n=46), and Venezuela (n=17) were enrolled and classified into two groups as follows: with AD or without AD. Clinical, paraclinical (including aquaporin-4 antibodies (AQP4-ab) status), magnetic resonance imaging (MRI), and prognosis data were analyzed and compared. Kaplan-Meier (KM) and the Nelson-Aalen estimator analyses were performed to estimate both time and the cumulative hazard risk of disability reaching an EDSS≥4; and time for the first recurrence. RESULTS: Out of 140 patients, 33 (23.5%) patients had associated an AD at presentation. The most frequent associated AD was Hashimoto disease (n=10) followed by lupus (n=7) and Sjogren's syndrome (n=6). However, rituximab use (42.4% vs. 21.5%, p=0.02), female gender (82.2% vs. 100%, p=0.006), corticospinal lesions on MRI (0% vs. 12.5%, p=0.01) at onset, and positivity for antinuclear antibodies (21.2% vs. 48.4%, p=0.03) were significantly associated with NMOSD patients with AD in comparison to NMOSD patients without AD. No differences were found in other clinical and paraclinical aspects between groups. KM and Nelson-Aalen estimator analyses did not show differences between groups. CONCLUSION: NMOSD patients associated with AD were observed in 23.5%. In addition, NMOSD patients with and without associated AD were similar in most evaluated features.

Disease activity after discontinuation of disease-modifying therapies in patients with multiple sclerosis in Argentina: data from the nationwide registry RelevarEM.

INTRODUCTION: The discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is commonly seen in real-world settings due to several factors. AREA COVER: The aim of this study is to describe the frequency of disease activity after discontinuation of DMTs in MS patients included in the Argentinean MS and NMOSD registry. DISCUSION: Patients with relapsing remitting MS (RRMS) and active secondary progressive MS (SPMS) were included based on the following criteria: they discontinued treatment for more than 6 months, they had been treated with a DMT for ≥2 years, and they had at least 6 months of follow-up in the registry after discontinuation. Demographic and clinical data were collected. Disease activity during follow-up was defined as the presence of a clinical relapse or a new magnetic resonance (MRI) lesion (either new lesions on T2-weighted sequence and/or contrast enhancement). Bivariate analysis was applied to identify clinical and demographic factors related to disease activity. CONCLUSION: We included 377 patients (75.5% RRMS, 22.5% SPMS) who had discontinued DMTs. The mean (SD) follow-up after discontinuation was 15.7 (7.9) months. After discontinuation, the presence of relapse was detected in 18.8% and 3.5% in RRMS and SPMS, respectively; and new MRI activity in 22% and 3.5%, respectively. We found that higher risk of relapse and MRI activity was associated with younger age (p < 0.001), shorter disease duration (p < 0.001), and RRMS phenotype (p = 0.006). Males showed higher MRI activity (p 0.011). This study provides real-world data that can guide physicians when considering discontinuation of DMTs.

Disability outcomes in NMOSD and MOGAD patients: data from a nationwide registry in Argentina.

The objective was to evaluate time to reach an EDSS of 4, 6, and 7 in NMOSD and MOGAD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03,375,177). METHODS: NMOSD patients diagnosed according to 2015 criteria and with MOGAD were identified. Patients with at least 3 years of follow-up and periodic clinical evaluations with EDSS outcomes were included. AQP4-antibody and MOG-antibody status was recorded, and patients were stratified as seropositive and seronegative for AQP4-antibody. EDSS of 4, 6, and 7 were defined as dependent variables. Log rank test was used to identify differences between groups. RESULTS: Registry data was provided for a total of 137 patients. Of these, seventy-five presented AQP4-ab-positive NMOSD, 45 AQP4-ab-negative NMOSD, and 11 MOGAD. AQP4-ab status was determined by cell-based assay (CBA) in 72% of NMOSD patients. MOG-ab status was tested by CBA in all cases. Mean time to EDSS of 4 was 53.6 ± 24.5 vs. 63.1 ± 32.2 vs. 44.7 ± 32 months in seropositive, seronegative NMOSD, and MOGAD, respectively (p = 0.76). Mean time to EDSS of 6 was 79.2 ± 44.3 vs. 75.7 ± 48.6 vs. 54.7 ± 50 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.23), while mean time to EDSS of 7 was 86.8 ± 54 vs. 80.4 ± 51 vs. 58.5 ± 47 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.39). CONCLUSION: No differences were observed between NMOSD (seropositive and seronegative) and MOGAD in survival curves.

Brain volume loss and physical and cognitive impairment in naive multiple sclerosis patients treated with fingolimod: prospective cohort study in Buenos Aires, Argentina.

BACKGROUND: The percentage of brain volume loss (PBVL) has been classically considered as a biomarker in multiple sclerosis (MS). OBJECTIVE: The objective of the present study was to analyze if the PBVL during the 1st year after the onset of the disease predicts physical and cognitive impairment (CI). METHODS: Prospective study that included naïve patients without cognitive impairment who initiated MS treatment with fingolimod. Patients were followed for 3 years and relapses, expanded disability status scale (EDSS) progression (defined as worsening of 1 point on the EDSS), the annual PBVL (evaluated by structural image evaluation using normalization of atrophy [SIENA]), and the presence of CI were evaluated. Cognitive impairment was defined in patients who scored at least 2 standard deviations (SDs) below controls on at least 2 domains. The PBVL after 1 year of treatment with fingolimod was used as an independent variable, while CI and EDSS progression at the 3rd year of follow-up as dependent variables. RESULTS: A total of 71 patients were included, with a mean age of 35.4 ± 3 years old. At the 3rd year, 14% of the patients were classified as CI and 6.2% had EDSS progression. In the CI group, the PBVL during the 1st year was - 0.52 (±0.07) versus -0.42 (±0.04) in the no CI group (p < 0.01; odds ratio [OR] = 2.24; 95% confidence interval [CI]: 1.72-2.44). In the group that showed EDSS progression, the PBVL during the 1st year was - 0.59 (±0.05) versus - 0.42 (±0.03) (p < 0.01; OR = 2.33; 95%CI: 1.60-2.55). CONCLUSIONS: A higher PBVL during the 1st year in naïve MS patients was independently associated with a significant risk of CI and EDSS progression.

ANTECEDENTES: A porcentagem de perda de volume cerebral (PPVC) é um biomarcador na esclerose múltipla (EM). OBJETIVO: Analisar se a PPVC durante o 1° ano após o início da doença prediz deterioração física (DF) e cognitiva (DC) em pacientes com EM. MéTODOS: Estudo de coorte prospectivo que incluiu pacientes recém-diagnosticados sem comprometimento cognitivo que iniciaram tratamento com fingolimode. Os pacientes foram acompanhados por 3 anos, sendo avaliados a presença de recidivas, progressão da Escala Expandida do Estado de Incapacidade (EDSS, na sigla em inglês) (definida como agravamento de 1 ponto na EDSS), o PPVC anual (avaliado pela avaliação de imagem estrutural de atrofia normalizada [SIENA, na sigla em inglês) e a presença de DC (avaliada no início do estudo e nos 2° e 3° anos). O PPVC no 1° ano de tratamento com fingolimode foi utilizado como variável independente. RESULTADOS: foram incluídos 71 pacientes com idade média de 35,4 ± 3 anos. No 3° ano, 14% dos pacientes tiveram DC e 6,2% tiveram progressão de EDSS. No grupo DC, o PPVC durante o 1o ano foi - 0,52 (±0,07) versus - 0,42 (±0,04) no grupo sem DC (p < 0,01; razão de probabilidades [OR, na sigla em inglês] = 2,24; intervalo de confiança [IC] de 95%: 1,72­2,44). No grupo que apresentou progressão da EDSS, o PPVC durante o 1° ano foi de - 0,59 (±0,05) versus - 0,42 (±0,03) (p < 0,01; OR = 2,33; IC95%: 1,60­2,55). CONCLUSõES: Um maior PPVC durante o 1° ano foi associado a um risco significativo de progressão de DC e EDSS durante o seguimento.

Incidence of COVID-19 after vaccination in people with multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

The objective of the study was to evaluate the incidence of COVID-19 after complete vaccination in people with multiple sclerosis (PwMS) included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). METHODS: cohort study conducted between May 2021 and December 2021. The primary outcome was the appearance of infection during the follow-up time (at least three months after complete vaccination (second dose)). Data was collected through the contact between the treating physician and the patient. Specific information was requested (date, symptoms, need for hospitalization, ventilatory assistance, treatment, and evolution). The contact was made every 30 days during the period of 3 months after the full dose vaccination. A positive COVID-19 case was defined according to the definition established by the Ministry of Health in Argentina. Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density. RESULTS: A total of 576 PwMS were included, mean age 45.2 ± 13 years, 432 (75%) RRMS, 403 (70%) were female. The mean and median time of follow-up after the second dose was 91 ± 17 and 94 ± 21 days respectively. Most frequent first and second dose received was Astra-Zeneca vaccine, followed by Sputnik V vaccine. During follow-up a total of twenty COVID-19 cases were observed for a total exposure time of 39,557 days. The overall cumulative incidence for the observed period was 3.4% (SE 0.4%) with an overall incidence density of 5 × 10.000 patients/day (95%CI 0.7-12). We observed more cases in woman than men with an incidence density of 6 × 10.000 patients/day (95%CI 0.9-9) vs. 3 × 10.000 patients/day (95%CI 0.2-6) respectively, but not significantly different (IRR 1.7 95% CI 0.56-7.37 p = 0.15). CONCLUSION: we found an incidence density of breakthrough COVID-19 infection of 5 × 10.000 patients/day (95%CI 0.7-12) after vaccination in Argentina.

Brain volume loss and physical and cognitive impairment in naïve multiple sclerosis patients treated with fingolimod: prospective cohort study in Buenos Aires, Argentina / Perda de volume cerebral e comprometimento físico e cognitivo em pacientes recém-diagnosticados com esclerose múltipla tratados com fingolimode: estudo de coorte prospectivo em Buenos Aires, Argentina

Abstract Background The percentage of brain volume loss (PBVL) has been classically considered as a biomarker in multiple sclerosis (MS). Objective The objective of the present study was to analyze if the PBVL during the 1st year after the onset of the disease predicts physical and cognitive impairment (CI). Methods Prospective study that included naïve patients without cognitive impairment who initiated MS treatment with fingolimod. Patients were followed for 3 years and relapses, expanded disability status scale (EDSS) progression (defined as worsening of 1 point on the EDSS), the annual PBVL (evaluated by structural image evaluation using normalization of atrophy [SIENA]), and the presence of CI were evaluated. Cognitive impairment was defined in patients who scored at least 2 standard deviations (SDs) below controls on at least 2 domains. The PBVL after 1 year of treatment with fingolimod was used as an independent variable, while CI and EDSS progression at the 3rd year of follow-up as dependent variables. Results A total of 71 patients were included, with a mean age of 35.4 ± 3 years old. At the 3rd year, 14% of the patients were classified as CI and 6.2% had EDSS progression. In the CI group, the PBVL during the 1st year was-0.52 (± 0.07) versus-0.42 (± 0.04) in the no CI group (p < 0.01; odds ratio [OR] = 2.24; 95% confidence interval [CI]: 1.72-2.44). In the group that showed EDSS progression, the PBVL during the 1st year was - 0.59 (± 0.05) versus - 0.42 (± 0.03) (p < 0.01; OR = 2.33; 95%CI: 1.60-2.55). Conclusions A higher PBVL during the 1st year in naïve MS patients was independently associated with a significant risk of CI and EDSS progression.

Resumo Antecedentes A porcentagem de perda de volume cerebral (PPVC) é um biomarcador na esclerose múltipla (EM). Objetivo Analisar se a PPVC durante o 1° ano após o início da doença prediz deterioração física (DF) e cognitiva (DC) em pacientes com EM. Métodos Estudo de coorte prospectivo que incluiu pacientes recém-diagnosticados sem comprometimento cognitivo que iniciaram tratamento com fingolimode. Os pacientes foram acompanhados por 3 anos, sendo avaliados a presença de recidivas, progressão da Escala Expandida do Estado de Incapacidade (EDSS, na sigla em inglês) (definida como agravamento de 1 ponto na EDSS), o PPVC anual (avaliado pela avaliação de imagem estrutural de atrofia normalizada [SIENA, na sigla em inglês) e a presença de DC (avaliada no início do estudo e nos 2° e 3° anos). O PPVC no 1° ano de tratamento com fingolimode foi utilizado como variável independente. Resultados foram incluídos 71 pacientes com idade média de 35,4 ± 3 anos. No 3° ano, 14% dos pacientes tiveram DC e 6,2% tiveram progressão de EDSS. No grupo DC, o PPVC durante o 1o ano foi - 0,52 (± 0,07) versus - 0,42 (± 0,04) no grupo sem DC (p<0,01; razão de probabilidades [OR, na sigla em inglês] =2,24; intervalo de confiança [IC] de 95%: 1,72-2,44). No grupo que apresentou progressão da EDSS, o PPVC durante o 1° ano foi de - 0,59 (± 0,05) versus - 0,42 (± 0,03) (p < 0,01; OR = 2,33; IC95%: 1,60-2,55). Conclusões Um maior PPVC durante o 1° ano foi associado a um risco significativo de progressão de DC e EDSS durante o seguimento.

Preferences for Disease-Modifying Therapies in Argentina: Cross-Sectional Conjoint Analysis of Patients and Neurologists.

OBJECTIVES: The objective of this study was to determine by a conjoint analysis the preferences for a range of disease-modifying treatment attributes in patients with multiple sclerosis (MS) and treating neurologists. METHODS: This was a cross-sectional study throughout Argentina between August 2020 and February 2021. Participating patients were adults with relapsing-remitting MS, who had received a long-term specific disease-modifying treatment for at least the past 3 months and their treating neurologist. Patients and neurologist were sampled from the Argentinean MS patient registry (RelevarEM). We applied the methodology of conjoint analysis. Patient preferences for hypothetical treatment were collected from the overall sample and from stratified subgroups according to the expanded disability status scale (EDSS) score. An ordinary least squares regression model was used to estimate parameters. RESULTS: A total of 275 patients from 25 centers (31 principal investigators) were included, mean age was 43.2 ± 10.9 years, 59.6% were female, and mean EDSS was 3.1 ± 2. For the entire sample, we observed that patients had higher preferences for treatments with lower side effect risks (28.7 relative preference [RP]), lower frequency of administration (21.4 RP), and higher impact on relapses (19.6 RP). Patients with a higher EDSS give significantly greater importance to a less frequent administration regime and the oral route than patients with a lower EDSS (23.5 RP vs 20.1 [P =.02] and 17.1 vs 15.3 [P =.03], respectively). For neurologists, the most important attribute was to prevent disease progression (RP 29.3). CONCLUSION: Our study contributes to the understanding of treatment selection preferences from the perspectives of both patient and neurologists.