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.

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.

Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study / Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto.

Introduction: Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective: To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods: We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results: Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions: We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

Introducción: El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo: Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos: Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados: Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones: Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto / Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study

Introducción. El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo. Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos. Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados. Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones. Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Introduction. Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective. To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods. We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results. Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions. We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

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.

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.

HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population.

OBJECTIVE: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia. METHODS: In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR. Mitochondrial hypervariable region 1 was amplified and haplogroups were determined using HaploGrep software. Genomic ancestry was estimated by genotyping a panel of ancestry informative markers. To test the association of HLA polymorphisms and MS, we ran separate multivariate logistic regression models. Bonferroni correction was used to account for multiple regression tests. RESULTS: A total of 100 patients with MS (mean age 40.4 ± 12 years; 70% females) and 200 healthy controls (mean age 37.6 ± 11 years; 83.5% females) were included in the analysis. Ancestry proportions and haplogroup frequencies did not differ between patients and controls. HLA-DRB1*15 was present in 31% of cases and 13.5% of controls, whereas HLA-DRB1*14 was present in 5% of cases and 15.5% of controls. In the multivariate model, HLA-DRB1*15 was significantly associated with MS (odds ratio [OR] = 3.05, p < 0.001), whereas HLA-DRB1*14 was confirmed as a protective factor in our population (OR = 0.16, p = 0.001). CONCLUSIONS: This study provides evidence indicating that HLA-DRB1*15 allele confers susceptibility to MS and HLA-DRB1*14 allele exerts resistance to MS in a highly admixed population. This latter finding could partially explain the low prevalence of MS in Bogotá, Colombia.