Real-World Effectiveness and Safety of Cladribine in Multiple Sclerosis: Longitudinal Data From the Nationwide Registry in Argentina.

OBJECTIVE: The aim was to evaluate patient profiles, effectiveness and safety of cladribine (CLAD) in patients with relapsing-remitting multiple sclerosis in Argentina. METHODS: This was a substudy included in RelevarEM (MS and neuromyelitis optica registry in Argentina, NCT03375177). Patients with MS who received CLAD tablets and were followed up for at least 24 months were included. Clinical evaluations every 3 months collect information about: a) clinical relapses; b) progression of physical disability, evaluated through Expanded Disability Status Scale, and c) new lesions found in the magnetic resonance imaging. Lymphopenia was evaluated during the follow-up and defined as grade 1: absolute lymphocyte count (ALC) 800-999/µL; grade 2: ALC 500-799/µL; grade 3: ALC 200-499/µL and grade 4: ALC <200/µL. RESULTS: A total of 240 patients were included from 19 centers from Argentina. The mean annualized relapse rate during the 12-month pre-CLAD initiation was 1.19 ± 0.56 versus 0.22 ± 0.18 at month 12 and 0.19 ± 0.15 at month 24 (P < 0.001). A total of 142 (59.2%) fulfilled the criteria of disease activity during the 12 months before treatment initiation, whereas 27 (11.3%) fulfilled it at month 12 and 38 (15.8%) at month 24, P < 0.001. Regarding no evidence of disease activity (NEDA), 202 (84.2%) patients achieved NEDA status at month 12 and 185 (77%) at month 24. The most frequent incidence density of lymphopenia for course 2 observed was also for grade 1, 6.1 (95% confidence interval [CI] = 5.5-7.1). The overall incidence density of lymphopenia grade 4 was 0.1 (95% CI = 0.06-0.19). CONCLUSION: This information will help when choosing the best treatment option for Argentinean patients.

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.

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.

Shared decision making in the treatment of multiple sclerosis: A consensus based on Delphi methodology.

Shared decision making is a way of incorporating patients' preferences and values into the decisions regarding the treatment and follow-up plan for the condition that affects them. It is currently applied mainly in the context of chronic disorders for which there is no cure available but nevertheless many therapeutic alternatives, such as multiple sclerosis (MS). Current views and opinions on shared decision making for the treatment of MS are discussed in this consensus based on a modified Delphi method that included a group of neurologists from Argentina. A set of statements was defined by the experts and seeks to serve as a guide to apply this concept in clinical practice.

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.

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.

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.

Rebound activity after fingolimod cessation: A case - control study.

BACKGROUND: There has been an increase in the number of reports of multiple sclerosis (MS) rebound activity (RA), which is usually defined as a severe disease reactivation after natalizumab or fingolimod withdrawal that exceeds pre-treatment baseline inflammatory activity. The frequency and risk factors that could predict RA remain unknown. Fingolimod is currently the most frequently prescribed disease modifying therapy for MS in Argentina, so that there is a need to determine possible predictors of RA. OBJECTIVES: To identify risk factors for developing RA after fingolimod cessation; to describe RA characteristics, management and evolution. METHODS: The study was a multicenter, retrospective, case-control study of patients with MS who had discontinued fingolimod and were followed up to nine months after discontinuation. Demographic, clinical and paraclinical data was extracted, including age, gender, MS phenotype, reason for discontinuation, number of relapses during the year prior to suspension, time treated with fingolimod, EDSS before, during and after rebound, MRI findings. RESULTS: 26 cases of RA were matched 1:1 with patients without RA. The median time elapsed to RA was 50 days. 68% showed worsening of the EDSS in the evaluation at 3 months of RA. When compared with the control group, no difference was found in terms of age, gender, phenotype, EDSS at the moment of suspension, reason for discontinuation, number of relapses in the previous year, and time on therapy. CONCLUSION: In this case-controlled study, no risk factors could be identified to predict RA after fingolimod cessation. Further controlled, prospective, better powered studies are needed to confirm these findings.

Evaluation of the times of disability progression and related factors in patients with primary progressive multiple sclerosis from Argentina.

Background PPMS (primary progressive multiple sclerosis) patients represent less than 10% of MS patients in Argentina, men and women were similarly affected and most of them had a severe functional impairment. More rapid progression has been reported in males, but this is not the case in all datasets. The main objective of our study was to determine the time to EDSS (Expanded disability Status Scale) 4, 6 and 7 in PPMS patients. We also compared the times to reach these EDSS in men and women and aimed to identify factors associated with the disability progression. Method This cohort of patients with diagnosis of PPMS (n = 253) was selected from follow-up recorded in the RelevarEM registry database. Result The median times to EDSS 4, 6 and 7 were 24 (IQR 12-48), 72 (IQR 36-96) and 96 (IQR 60-120) months, respectively. Comparison of the survival curves to EDSS 4, 6 and 7 according to gender did not show significant differences (p = 0.33, p = 0.55 and p = 0.59). There is no evidence of an association between the clinical adjustment variables (sex, age >40 years at diagnosis, EDSS > 3 at onset and multifocal MS symptoms at disease onset) and the time of arrival at the EDSS 4, 6 and 7. Conclusion Severe disability was observed six years after the onset of symptoms. No association was found between the studied factors and the time to arrival to severe disability.

Accumulative risk of clinical event in high-risk radiologically isolated syndrome in Argentina: data from the nationwide registry RelevarEM.

INTRODUCTION: We aimed to analyze the accumulative risk of MRI and OB factors for evolution from RIS to MS in subjects included in the Argentinean MS registry (NCT03375177). METHODS: RIS subjects were identified according to RIS diagnosis criteria. Subjects were longitudinally followed with clinical and MRI at intervals of 6 months. Time from RIS identification to the first clinical event was estimated using Kaplan-Meier. Multivariable Cox regression models were created to assess the independent predictive value of demographic characteristics, as well as clinical, OB and MRI data on time to the first clinical event. The single and increased risk factor of evolution of RIS was quantified. RESULTS: A total of 88 RIS subjects, mean follow-up time 42 ± 4 months were included. 39 (44.3%) and 23 (26.1%) had a new MRI lesion or a clinical event, respectively, during the follow-up. OB (HR 5.9, 95% CI 1.29-10.1, p = 0.004), infratentorial lesions (HR 3.7, 95% CI 1.09-7.5) and spinal cord lesions (HR 5.3, 95% CI 1.4-8.2, p = 0.01) at RIS identification were independent predictors associated with a subsequent clinical event. The accumulative risk showed that when two of the three factors (OB, infratentorial or spinal cord lesions) were present the HR was 10.4, 95% CI 4.4-22, p < 0.001, and when three factors were present, it was HR 15.6, 95% CI 5.7-28, p < 0.001 for a relapse. CONCLUSION: The presence of three factors significantly increased the risk of clinical event; high-risk subjects should probably be managed by a different approach than those used for individuals without high-risk factors.

Seasonal variation in attacks of neuromyelitis optica spectrum disorders and multiple sclerosis: Evaluation of 794 attacks from a nationwide registry in Argentina.

BACKGROUND: Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders. METHODS: A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients. Patients with complete relapse data (date, month and year) at onset and during follow-up were included. Attack counts were analyzed by month using a Poisson regression model with the median monthly attack count used as reference. RESULTS: A total of 551 patients (431 MS and 120 NMOSD), experiencing 236 NMOSD-related attacks and 558 MS-related attacks were enrolled. The mean age at disease onset in NMOSD was 39.5 ± 5.8 vs. 31.2 ± 9.6 years in MS (p < 0.01). Mean follow-up time was 6.1 ± 3.0 vs. 7.4 ± 2.4 years (p < 0.01), respectively. Most of the included patients were female in both groups (79% vs. 60%, p < 0.01). We found a peak of number of attacks in June (NMOSD: 28 attacks (11.8%) vs MS: 33 attacks (5.9%), incidence rate ratio 1.82, 95%CI 1.15-2.12, p = 0.03), but no differences were found across the months in both disorders when evaluated separately. Strikingly, we observed a significant difference in the incidence rate ratio of attacks during the winter season when comparing NMOSD vs. MS (NMOSD: 75 attacks (31.7%) vs MS: 96 attacks (17.2%), incidence rate ratio 1.82, 95%CI 1.21-2.01, p = 0.02) after applying Poisson regression model. Similar results were observed when comparing the seropositive NMOSD (n = 75) subgroup vs. MS. CONCLUSIONS: Lack of seasonal variation in MS and NMOSD attacks was observed when evaluated separately. Future epidemiological studies about the effect of different environmental factors on MS and NMOSD attacks should be evaluated prospectively in Latin America population.

Assessing attacks and treatment response rates among adult patients with NMOSD and MOGAD: Data from a nationwide registry in Argentina.

We aimed to examine treatment interventions implemented in patients experiencing neuromyelitis optica spectrum disorders (NMOSD) attacks (frequency, types, and response). METHODS: Retrospective study. Data on patient demographic, clinical and radiological findings, and administered treatments were collected. Remission status (complete [CR], partial [PR], no remission [NR]), based on changes in the EDSS score was evaluated before treatment, during attack, and at 6 months. CR was analyzed with a generalized estimating equations (GEEs) model. RESULTS: A total of 131 patients (120 NMOSD and 11 myelin oligodendrocyte glycoprotein-antibody-associated diseases [MOGAD]), experiencing 262 NMOSD-related attacks and receiving 270 treatments were included. High-dose steroids (81.4%) was the most frequent treatment followed by plasmapheresis (15.5%). CR from attacks was observed in 47% (105/223) of all treated patients. During the first attack, we observed CR:71.2%, PR:16.3% and NR:12.5% after the first course of treatment. For second, third, fourth, and fifth attacks, CR was observed in 31.1%, 10.7%, 27.3%, and 33.3%, respectively. Remission rates were higher for optic neuritis vs. myelitis (p < 0.001). Predictor of CR in multivariate GEE analysis was age in both NMOSD (OR = 2.27, p = 0.002) and MOGAD (OR = 1.53, p = 0.03). CONCLUSIONS: This study suggests individualization of treatment according to age and attack manifestation. The outcome of attacks was generally poor.

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT03375177). METHODS: The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset. RESULTS: A total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively). CONCLUSION: 3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.

An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed. Methods: In this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes. Results: NLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; p<0.0001). Regardless of immunosuppressant's initiation at disease onset, NLR remained higher in NMOSD patients at 12 (2.8 ± 1.3; p<0.0001) and 24 (3.1 ± 1.6; p<0.0001) months. No association was found at 12 and 24 months between the log-transformed NLR and the presence of relapses, new/enlarging and/or contrast-enhancing MRI lesions, and/or physical disability. Conclusions: In this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.

BACKGROUND: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. OBJECTIVE: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. METHODS: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. RESULTS: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. CONCLUSION: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.

What percentage of AQP4-ab-negative NMOSD patients are MOG-ab positive? A study from the Argentinean multiple sclerosis registry (RelevarEM).

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been described in aquaporin-4-antibodies(AQP4-ab)-negative neuromyelitis optica spectrum disorder (NMOSD) patients. We aimed to evaluate the percentage of AQP4-ab-negative NMOSD patients who are positive for MOG-ab in a cohort of Argentinean patients included in RelevarEM (Clinical Trials registry number NCT03375177). METHODS: RelevarEM is a longitudinal, strictly observational multiple sclerosis (MS) and NMOSD registry in Argentina. Of 3031 consecutive patients (until March 2020), 165 patients with phenotype of suspected NMOSD, whose relevant data for the purpose of this study were available, were included. Data on demographic, clinical, paraclinical and treatment in AQP4-ab (positive, negative and unknown) and MOG-ab (positive and negative) patients were evaluated. RESULTS: A total of 165 patients (79 AQP4-Ab positive, 67 AQP4-Ab negative and 19 unknown) were included. Of these, 155 patients fulfilled the 2015 NMOSD diagnostic criteria. Of 67 AQP4-Ab-negative patients, 36 (53.7%) were tested for MOG-Ab and 10 of them (27.7%) tested positive. Serum AQP4-ab levels were tested by means of cell-based assay (CBA) in 48 (35.2%), based on tissue-based indirect immunofluorescence assays in 58 (42.6%) and enzyme-linked immunosorbent assay in 4 (2.9%). All MOG-ab were tested by CBA. Optic neuritis (90%) was the most frequent symptom at presentation and optic nerve lesions the most frequent finding (80%) in neuroimaging of MOG-ab-associated disease. Of these, six (60%) patients were under immunosuppressant treatments at latest follow-up. CONCLUSION: We observed that 27.7% (10/36) of the AQP4-ab-negative patients tested for MOG-ab were positive for this antibody, in line with results from other world regions.

Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina / Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis

INTRODUCCIÓN: Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. OBJETIVO: Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. DESARROLLO: Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. CONCLUSIÓN: Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of formal consensus-RAND/UCLA method was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina

Usage trend of oral drugs for multiple sclerosis patients in Argentina.

INTRODUCTION: Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina. METHODS: A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time. RESULT: The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p <0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p<0.01) were independently associated with choice of oDMTs. CONCLUSION: This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina.