Clinical and demographic characteristics of male MS patients included in the national registry-RelevarEM. Does sex or phenotype make the difference in the association with poor prognosis?

BACKGROUND: In multiple sclerosis demographics there is a well-known female prevalence and male patients have been less specifically evaluated in clinical studies, though some clinical differences have been reported between sexes. OBJECTIVE: The objective of this study was to assess clinical and demographic differences between male and female patients included in the national Argentine MS Registry-RelevarEM. MATERIAL AND METHODS: This study was observational, retrospective, and was based on the data of 3099 MS patients included as of 04 April 2021. The statistical analysis plan included bivariate analyses with the crude data and also after adjustment for the MS phenotype, further categorized as progressive-onset MS or relapsing-onset MS. In the adjusted analysis, the Mantel-Haenszel odds ratio was compared to the crude odds ratio, to account for the phenotype as a confounder. RESULTS: The data from 1,074 (34.7%) men and 2,025 (65.3%) women with MS diagnosis were analysed. Males presented primary progressive disease two times more often than women (11% and 5%, respectively). In the crude analyses by sex, the presence of exclusively infratentorial lesions in the magnetic resonance imaging studies was more frequent in males than in females, but after adjustment by MS onset phenotype, such difference was only present in males with relapsing-onset MS (p = 0.00006). Similarly, worse Expanded Disability Status Scale scores were confirmed only in men with relapsing-onset disease after phenotype adjustment (p = 0.02). CONCLUSION: We did not find any statistically significant clinical or demographic difference between sexes when the progressive MS phenotype was specifically considered. However, the differences we found between the clinical phenotypes are in line with the literature and highlight the importance of stratifying the analyses by sex and phenotype when designing MS studies.

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.

Oral administration of methylprednisolone powder for intravenous injection dissolved in water to treat MS and NMOSD relapses during COVID-19 pandemic in a real-world setting.

BACKGROUND: Upon the COVID-19 pandemic emergence, safety concerns and logistic drawbacks stimulated the search for alternatives to pulse therapy at infusion centres to treat multiple sclerosis relapses. OBJECTIVE: To describe our experience treating multiple sclerosis relapses with a dilute injectable methylprednisolone powder orally administered, in a safe home-based environment and with totally virtual assessment and follow up via telemedicine. METHODS: Descriptive observational, retrospective, single-centre, open label, study in the real-world setting. RESULTS: Between August 2020 and March 2021, ten multiple sclerosis patients and one neuromyelitis optica spectrum disease patient, regularly assisted at our multiple sclerosis centre in Argentina, experienced twelve disease relapses (nine moderate/severe relapses and three mild relapses) and were treated with the oral dilute of injectable methylprednisolone powder pulses with good efficacy as well as adequate tolerance and safety profile. CONCLUSIONS: The oral pulse therapy based on the methylprednisolone powder dilution we describe is simple and comfortable to administer and can be an option in countries like Argentina, where the oral methylprednisolone formulation is not marketed. In these pandemic times, a home based and virtually monitored pulse therapy could represent a safe and effective alternative to manage relapses while minimizing the patient's risk of exposure to SARS-CoV-2.

Prevalence of Multiple Sclerosis in Rosario, Argentina.

BACKGROUND: The prevalence and incidence of Multiple Sclerosis have been increasing worldwide over the last decades. Most of the publications during the last years outstand the prevalence in Europe, North America and Latin America. In Argentina, data published on this topic is scarce and most of the studies took place in Buenos Aires. In a recent publication, we reported an MS prevalence rate of 30.3/100,000 in the overall extension of Santa Fe, Argentina, and in that study, we noticed that MS seemed to be more frequent in the southern region of the province. OBJECTIVE: In this study we aimed to estimate the prevalence of MS in Rosario (the third most populated district of Argentina), placed in the southeastern part of Santa Fe province. METHODS: This is a population based, cross-sectional study. We studied the members of the Province´s medical Care Program, a health maintenance organization of the public-sector employees that offers medical and health services to 567,819 members in the province 163,513 of whom have permanent residence in Rosario department, being a large representative sample. The selected prevalence date was 30 June 2019. Cases of MS were detected with a thorough search in the electronic databases of affiliates, linking and aggregating datasets. RESULTS: Seventy-nine MS cases were detected. The mean age was 47.7 (SD 13.5); female to male ratio was 3 to 1; the most frequent phenotype was relapsing-remitting (82.3%) followed by secondary-progressive (15.2%) and primary-progressive (2.5%). The crude prevalence rate of MS in Rosario as on 30 June 2019 was 48.3/100,000 inhabitants (95% CI: 48.28 - 48.35), 63.7/100,000 for females and 28.3/100,000 for males. The age-standardised MS prevalence rate was 43.4/100,000 inhabitants (95% CI:43.37 - 43.43) while the sex-standardised prevalence was estimated at 46.7/100,000 inhabitants (95% CI: 46.68 - 46.74). Making a proportional and linear projection to the total number of inhabitants, we deemed a total of 578 MS cases in Rosario, according to the 2010 census, and projected 620 cases by July 2019. CONCLUSION: This is the first study that provides epidemiological data of MS prevalence for Rosario. It confirms that there are differences in the distribution of MS in Santa Fe that favour the aggregation of cases in the southern part of the province. It also supplies updated and relevant data on the distribution of MS in Argentina and Latin America.

High birth weight and risk of multiple sclerosis: A multicentre study in Argentina.

BACKGROUND: Multiple sclerosis (MS) is now recognized as a multifactorial disease in which genetic and environmental factors intervene. Considerable efforts have been made to identify external risk factors present in childhood, adolescence and youth, though only a few perinatal risk factors have been positively associated with MS. Previously, we found an association between high birth weight and MS in male patients in a small study in Argentina. The present research was designed to further assess the association between high birth weight and MS in a larger sample of patients, using an extensive and validated general population database as control. METHODS: We present an analytical observational, multicentre, population-based, and case-control study. A total of 637 patients (cases) with confirmed MS diagnosis attending five MS specialized centres in Argentina were included. Birth weight (BW) data was recalled by the patient's mother, which is a validated approach. A two-way comparison was performed. First, we used the standard categories of high, adequate and low BW in grams. Then, we applied the weight percentile distribution to provide reproducible results for further research. For a proper assessment and comparison of variables, we adopted the guidelines of the American Academy of Pediatrics for neonate classification according to gestational weeks and to BW in grams. The neonate's BW distribution of the general population was used as control. For the purposes of the study, we adapted Urquía's et al. curves, which are based on an extensive database of all the live births registered in the country from 2003 to 2007. To measure the magnitude of the proportional differences between low, adequate and high BW, the odds ratio (OR) and their 95% confidence interval (CI) were estimated. The mean BW and percentile values for each sex were compared using a z-Normal test. The respective MS patients and general population BW distribution curves by sex were compared between each other. RESULTS: Cases and controls were comparable in their demographic, geographic and environmental characteristics. Males showed higher BW than females both in the MS patients and the general population groups. When we applied the sex stratified analysis separately, we found that males in the MS group showed an almost seven times higher risk of high birth weight than males from the general population (OR 6.58 [95% CI 4.81-8.99]). Female patients showed an almost five times higher risk of high BW than their respective controls (OR 4.5 [95% CI 3.06-6.58]). The comparison based on the BW percentile distribution confirmed that MS patients showed higher BW than the general population. This result reached statistical significance from the 75th percentile onwards for both sexes. CONCLUSION: In summary, our findings suggested that high BW could be one of the earliest risk factors for MS in life. If this results were reproduced in other centres, high birth weight would emerge as a novel and very early risk factor, potentially modifiable in utero or immediately postpartum, representing a unique opportunity to prevent the disease in future generations.

Consensus recommendations on the management of multiple sclerosis patients in Argentina.

INTRODUCTION: During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients. METHODS: A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process. CONCLUSIONS: The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina.

Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients.

One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina. METHODS: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients. CONCLUSIONS: The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina.