Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay. Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment. Design, Setting, and Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023. Exposures: Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year). Main Outcomes and Measures: Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed. Results: Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment. Conclusions and Relevance: The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors.

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

COVID-19 en pacientes con esclerosis múltiple: estudio observacional retrospectivo en un centro de referencia colombiano / COVID-19 in patients with multiple sclerosis: retrospective observational study in a reference center in Colombia

Introducción: En Colombia, la información sobre la frecuencia de presentación de la enfermedad por CO-VID-19 y sus desenlaces en personas con esclerosis múltiple (EM) es prácticamente inexistente. El objetivo de este estudio es describir la frecuencia, las características y los factores relacionados con la infección por COVID-19 en una muestra de pacientes con EM en Colombia. Materiales y métodos: Análisis descriptivo y retrospectivo de pacientes diagnosticados con criterios de esclerosis múltiple que acudieron a nuestro centro entre junio y octubre del año 2021. Los pacientes proporcionaron información sobre la infección por SARS-CoV-2 y su vacunación. Se analizaron los factores relacionados con la infección por COVID-19 mediante modelos de regresión logística binomial uni y multivariable. Resultados: Se analizaron 240 pacientes, de los cuales el 71 % eran mujeres, con una edad promedio de 34 años. La mayoría estaban en tratamiento con terapias modificadoras de la enfermedad y más del 80 % estaban vacunados. Sesenta y nueve pacientes declararon haber tenido COVID-19. En los modelos multivariables, la edad (OR 0,96; IC 95 % 0,93-0,99) fue el único factor asociado con una menor probabilidad de infección por COVID-19. Discusión: La infección por COVID-19 en pacientes con EM en Colombia parece ser independiente de las variables clínicas y de tratamiento y parece estar asociada con la menor edad. Conclusiones: Se requieren más estudios para evaluar el comportamiento del COVID-19 en pacientes con EM en el contexto colombiano.

Introduction: The information about the frequency of COVID-19 and its outcomes in people with Multiple Sclerosis (MS) in Colombia is practically non-existent. We aimed to describe the frequency characteristics and factors associated with of COVID-19 in a sample of patients with MS. Materials and methods: Descriptive and retrospective analysis of patients diagnosed with Multiple Sclerosis criteria who attended our center between June and October 2021. Patients provided information about SARS-CoV-2 infection and their vaccination. COVID-19 determinants were analyzed using uni-and multivariable binomial logistic regression models. Results: 240 patients were analyzed, of whom 71% were women, with a mean age of 34 years. The majority of patients were on disease-modifying therapies and over 80 % were vaccinated. 69 patients reported having had COVID-19. In multivariable models, age (OR 0.96; 95 % CI 0.93-0.99) was the only factor associated with a lower odds of COVID-19 infection. Discussion: COVID-19 infection in patients with MS in Colombia appears to be independent of clinical and treatment variables, and it appears to be associated with younger age. Conclusions: More studies are needed to assess the behavior of COVID-19 in MS patients from Colombia.

No seasonality in the risk of multiple sclerosis in an equatorial country: A case-control ecological study.

BACKGROUND: Multiple sclerosis risk has been shown to have seasonal variations that are more pronounced in higher latitudes. However, this phenomenon has not been adequately studied near the Equator. OBJECTIVE: To explore the risk of multiple sclerosis associated with month, season of birth, and sunlight exposure variables in Colombia. METHODS: In this case-control study, 668 multiple sclerosis cases were matched to 2672 controls by sex and age. Association of multiple sclerosis with each month/season of birth and sunlight exposure variables was estimated with multilevel mixed-effects logistic regression and ecological regression models, respectively. Seasonality in the births of multiple sclerosis was assessed with a non-parametric seasonality test. RESULTS: We found a higher probability of multiple sclerosis in September (0.25; 95% confidence interval (CI) = 0.21-0.31) and lower in March (0.15; 95% CI = 0.10-0.18), which turned non-significant after a multiple comparisons test. Sunlight exposure variables had no significant effect on the risk of MS, and the tests of seasonality in the births of MS did not show significant results. CONCLUSION: Our results show no seasonality in the risk of multiple sclerosis near the Equator, supporting the hypothesis that this phenomenon is latitude dependent.

Gender disparities in multiple sclerosis research and leadership: A Colombian perspective.

Background: The neurological academic field is an illustrative example of persistent gender-related disparities reflected in compensation, funding, leadership, promotion, publishing, and recognition. Several studies indicate that neurology is one of the most underrepresented specialties with female physicians as first authors, but also has one of the highest gender payment gaps. Neglecting the role of women in academic leadership positions hinders the visibility and recognition of research and leadership in multiple sclerosis (MS). Increasing diversity within academia has positive effects, such as widening focus and expanding the plurality of research outputs. The gender gap and visibility of female MS clinicians and researchers remains an unexplored research topic in our country despite the rising number of female neurologists. Objective: This study aims to establish the gender distribution between researchers and clinical neurologists in multiple sclerosis in Colombia and raise awareness about gender disparities in this area. Methods: We applied a cross-sectional survey study of Colombian neurologists and neurology residents currently members of the Colombian Neurology Association. Mean and standard deviation (SD) were used for quantitative variables and frequency for qualitative variables. To evaluate the influence of gender, logarithmic regression was used. Data were analyzed in SPSS 26. Results: A total of 201 participants agreed to complete the survey, most of whom were female (n = 135, 67.2%). All the Colombian regions were represented in the survey. Of those surveyed, 31.5% (n = 64) had an interest in demyelinating diseases and MS, of which 46.8% (n = 30) were female. Of the women with MS training, only 50% (n =5) had more than three publications as the first author of a scientific article compared to men (n = 5, 83%). After adjusting the number of publications by gender, there were no significant differences between men and women (median 2.0[2, 1.21] vs. 2[2, 0.5], p = 0.904). However, only 16.6% (n = 5) of women had a visible academic, leadership, or teaching position compared with men 75.7% (n = 25). When adjusting the salary income by gender, we found a statistically significant difference between women and men (median 2.0 [5, 1.47] vs. 3 [5, 1.65], p = 0.006). Women in MS earned between USD 2,500 and 3,800 per month; while men earned between USD 3,800 to 5,070. Conclusion: Despite a higher number of female neurologists trained in MS in Colombia, our data suggest considerable differences and gender gaps with regard to diverse opportunities at the academic, salary promotion, leadership, teaching, and recognition levels between male and female MS neurologists.

Fertility preferences and unmet need for family planning in women with multiple sclerosis.

Background: Most women with multiple sclerosis (MS) have childbearing potential. Although fertility and pregnancy are not affected by MS, the fertility preferences of women with MS can change due to the risk of complications for the mother and/or adverse pregnancy outcomes resulting from the disease or its treatment. Objectives: To describe fertility preferences (FPs) and their associated factors, to estimate the Unmet Need for Family Planning (UNFP), use of contraceptives, and history of exposure to disease-modifying therapies (DMTs) during pregnancy in women with MS. Methods: In a cross-sectional observational study, a random sample of women with MS were surveyed with the FP subset of the Demographic and Health Survey of Colombia. Factors associated with FP were evaluated through bivariate and logistic regression analysis. The proportion of pregnancies exposed to DMTs, UNFP, and use of contraceptives was estimated. Results: Of the 141 women interviewed, 101 women had childbearing potential, of whom 49 did not want to have children, 38 were sterilized, 33 wanted to have more children, 19 were undecided, and 2 stated they were unable to bear children (menopause or hysterectomy). No MS-related variables were associated with the preference to have more children. Age (OR 0.91; 95% CI 0.84-0.98) and the number of children (OR 0.23; 95% CI 0.09-0.58) decreased the likelihood of desire for children. Of 116 sexually active women, 87.06 % (101) were using contraceptives, and among them, four were using fertility awareness methods and withdrawal. The UNFP was estimated at 6.03% and was not significantly different from the general population. Eighty-two pregnancies were identified, of which 48 occurred after diagnosis, and 25 were exposed to DMTs. Conclusion: Fertility preference in women with MS is not associated with clinical variables. A large proportion of women choose not to have children and prefer to use permanent contraceptive methods. Although the frequency of contraceptive use was high, some women have the UNFP and use low-efficacy contraceptive methods, which may result in unplanned pregnancies.

Delayed diagnosis of multiple sclerosis in a low prevalence country.

Background: Early diagnosis and treatment of multiple sclerosis (MS) is crucial to avoid future disability. The factors that influence diagnostic delay in low prevalence settings have been poorly studied.Objectives: To evaluate the factors associated with a delayed diagnosis of MS after the symptomatic onset.Methods: Clinical records of confirmed MS patients were reviewed. Diagnostic delay was calculated by subtracting the date of onset from the date of diagnosis and categorized as early and delayed, when below and above than 1 year. Logistic regression was performed to evaluate the likelihood of a delayed diagnosis according to age at first symptom, gender, type of the first symptom, progressive vs relapsing onset, diagnostic criteria prevailing at the time of symptom onset, comorbidities, and family history of MS.Results: Data of 525 (95.6%) from a cohort of 549 patients were analyzed. About 69.1% were women. The mean age was 43.2 years. About 86.3% had relapsing-remitting MS. The mean overall diagnostic delay was 3.07 years. About 45.7% of the patients had a delayed diagnosis, and it was dependent on the symptom and the diagnostic criteria prevailing at the onset. Multivariate logistic regression showed onset during the Schumacher (OR = 10.03 [95%CI 1.30-77.1], p = 0.027) and Poser (OR = 4.26 [95%CI 1.25-15.15], p = 0.021) years were associated with delayed MS diagnosis.Conclusions: MS onset before the McDonald diagnostic criteria era is associated with delayed diagnosis.

Multiple sclerosis coverage in the written media of a low prevalence country.

BACKGROUND: Awareness in the community is an important factor across a wide range of diseases and the communication media have an important role in its promotion. However, misinformation and misguide may take place heightening the expectations of people affected by chronic conditions such as multiple sclerosis (MS). This study explores media coverage of MS in a low prevalence country. METHODS: We identified the most important written media at national and local levels and performed a search in their digital archives and social media with the words "Multiple Sclerosis". The articles found were categorized as relevant, and non-relevant. We describe the total number, number of relevant and non-relevant articles published every year, since the earliest found until 2018. We identified the topics covered by the relevant articles and described their distribution and performed a quality evaluation of their content. RESULTS: We reviewed the archives of 20 sources. A total of 976 articles where MS was mentioned were reviewed (relevant: 143 [14.6%]; non-relevant: 833 [85.4%]). We observed a steady increase in the annual publication rate, from the first in 1991 up to 107 in 2018. The most frequent covered topic was disease modifying therapies and MS itself, and the least documented topic was rehabilitation. Most of the relevant articles had low quality scores. CONCLUSION: The media coverage of different topics MS has risen steadily since its first appearance in the early nineties. This should be encouraged, but caution should be held so misinformation is not propagated. We call for the public to discuss misleading information with their healthcare providers.