Gantenerumab for early Alzheimer's disease: a systematic review and meta-analysis.

INTRODUCTION: Gantenerumab is a monoclonal antibody targeting amyloid ß protein (Aß) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients. METHODS: MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis. RESULTS: A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; p = 0.008569; I2 = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; p = <0.000001; I2 = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; p = <0.000001; I2 = 0%), respectively. DISCUSSION: In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.

Preparedness of the Brazilian health-care system to provide access to a disease-modifying Alzheimer's disease treatment.

BACKGROUND: While the majority of patients with Alzheimer's disease resides in low and middle-income countries, little is known of their preparedness for emerging disease-modifying treatments. We analyze the preparedness of Brazil, one of the most populous middle-income countries, from a capacity and institutional preparedness perspective. METHODS: Desk research and 12 interviews for background and capacity data. Markov model to estimate wait times for access to treatment. FINDINGS: Brazil has no national dementia strategy or established pathway for evaluation of cognitive concerns, and dementia is typically diagnosed late if at all. While members of private health plans have ready access to elective specialty care, wait times in the public sector are long. Assuming potentially treatment-eligible patients are referred from primary to specialty care based on a brief cognitive exam and a blood test for the Alzheimer's pathology, available capacity will not be sufficient to match the projected demand. The biggest obstacle is availability of dementia specialist visits, and the effect of population growth and ageing means that the wait list for specialist appointment will continue to grow from around 400,000 in 2022 to over 2.2 million in 2040. We do not project substantial wait times for confirmatory biomarker testing and treatment delivery but note that this is a consequence of patients waiting for their specialist appointments. These queues will result in estimated persistent wait times for treatment of around two years on average with substantial differences between the public and private sectors, as capacity growth is insufficient to keep up with increasing demand. DISCUSSION: Our findings suggest that Brazil is ill-prepared to provide timely access to an Alzheimer's treatment with predicted wait times of about two years, largely because of a limited number of dementia specialists.

[Adherence to treatment of multiple sclerosis in a health care program]. / Adherencia al tratamiento de la esclerosis múltiple en un programa de atención médica.

Adherence to prescribed treatment in chronic diseases, as occurs in multiple sclerosis (MS), is a critical factor for a successful therapeutic response. The objective of this study was to evalua te the association between demographic variables and adherence to treatment of the population of MS patients in Argentina. A retrospective cohort study of MS patients who received treatment with disease-modifying drugs, included in the drug dispensing database of the National Care Medical Program: PAMI (Programa Asistencia Médica Integral), was conducted. Optimal adherence was defined as an acquisition of the drug greater than 80% during a 9-month follow-up. A total of 648 patients were included, mean age 55 years (IQR 46-64), 59.4% women. The mean adherence to treatment was 67% (IQR 44-89) and optimal adherence was documented only in 35.5% of cases. Adherence to injectable medications was 10% lower than that of oral drugs (p = 0.0001) and the use of original brands was associated with 7.4% greater adherence than with generic drugs (p = 0.001). In conclusion, adherence to treatment has been suboptimal. In the Patagonian region, the use of injectables and generic drugs was associated with lower adherence to therapy. These data are very important in order to planning socio-sanitary programs that aim to increase therapeutic adherence.

La adherencia al tratamiento prescrito en enfermedades crónicas, como ocurre en la esclerosis múltiple (EM), es un factor crítico para una respuesta terapéutica exitosa. El objetivo de este estudio fue evaluar la asociación entre las variables demográficas y la adherencia al tratamiento en una población de pacientes con EM en Argentina. Se realizó un estudio de cohorte retrospectivo de pacientes con EM que recibieron tratamiento con medicamentos modificadores de la enfermedad, incluidos en la base de datos de dispensación de medicamentos del Programa Nacional de Atención Médica: PAMI (Programa Asistencia Médica Integral). La adherencia óptima se definió como una adquisición del fármaco superior al 80% durante un seguimiento de 9 meses. Se incluyó un total de 648 pacientes, edad media 55 años (RIC 46-64), 59.4% mujeres. La adherencia media al tratamiento fue del 67% (RIC 44-89) y la adherencia óptima se documentó solo en el 35.5% de los casos. La adherencia a los medicamentos inyectables fue 10% menor que la de los medicamentos orales (p = 0.0001) y el uso de marcas originales se asoció con una adherencia 7.4% mayor que los medicamentos genéricos (p = 0.001). En conclusión, la adherencia al tratamiento ha sido subóptima. En la región patagónica, el uso de inyectables y de medicamentos genéricos se asoció con una menor adherencia terapéutica. Estos datos son muy importantes para planificar programas socio-sanitarios que tengan como objetivo aumentar la adherencia terapéutica.

Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: An international consensus statement.

In this consensus statement, we provide updated recommendations on multiple sclerosis (MS) management during the COVID-19 crisis and the post-pandemic period applicable to neurology services around the world. Statements/recommendations were generated based on available literature and the experience of 13 MS expert panelists using a modified Delphi approach online. The statements/recommendations give advice regarding implementation of telemedicine; use of disease-modifying therapies and management of MS relapses; management of people with MS at highest risk from COVID-19; management of radiological monitoring; use of remote pharmacovigilance; impact on MS research; implications for lowest income settings, and other key issues.

Adherencia al tratamiento de la esclerosis múltiple en un programa de atención médica / Adherence to treatment of multiple sclerosis in a health care program

Resumen La adherencia al tratamiento prescrito en enfermedades crónicas, como ocurre en la esclerosis múltiple (EM), es un factor crítico para una respuesta terapéutica exitosa. El objetivo de este estudio fue evaluar la asociación entre las variables demográficas y la adherencia al tratamiento en una población de pacientes con EM en Argentina. Se realizó un estudio de cohorte retrospectivo de pacientes con EM que recibieron tratamiento con medicamentos modificadores de la enfermedad, incluidos en la base de datos de dispensación de medicamentos del Programa Nacional de Atención Médica: PAMI (Programa Asistencia Médica Integral). La adherencia óptima se definió como una adquisición del fármaco superior al 80% durante un seguimiento de 9 meses. Se incluyó un total de 648 pacientes, edad media 55 años (RIC 46-64), 59.4% mujeres. La adherencia media al tratamiento fue del 67% (RIC 44-89) y la adherencia óptima se documentó solo en el 35.5% de los casos. La adherencia a los medicamentos inyectables fue 10% menor que la de los medicamentos orales (p = 0.0001) y el uso de marcas originales se asoció con una adherencia 7.4% mayor que los medicamentos genéricos (p = 0.001). En conclusión, la adherencia al tratamiento ha sido subóptima. En la región patagónica, el uso de inyectables y de medicamentos genéricos se asoció con una menor adherencia terapéutica. Estos datos son muy importantes para planificar programas socio-sanitarios que tengan como objetivo aumentar la adherencia terapéutica.

Abstract Adherence to prescribed treatment in chronic diseases, as occurs in multiple sclerosis (MS), is a critical factor for a successful therapeutic response. The objective of this study was to evaluate the association between demographic variables and adherence to treatment of the population of MS patients in Argentina. A retrospective cohort study of MS patients who received treatment with disease-modifying drugs, included in the drug dispensing database of the National Care Medical Program: PAMI (Programa Asistencia Médica Integral), was conducted. Optimal adherence was defined as an acquisition of the drug greater than 80% during a 9-month follow-up. A total of 648 patients were included, mean age 55 years (IQR 46-64), 59.4% women. The mean adherence to treatment was 67% (IQR 44-89) and optimal adherence was documented only in 35.5% of cases. Adherence to injectable medications was 10% lower than that of oral drugs (p = 0.0001) and the use of original brands was associated with 7.4% greater adherence than with generic drugs (p = 0.001). In conclusion, adherence to treatment has been suboptimal. In the Patagonian region, the use of injectables and generic drugs was associated with lower adherence to therapy. These data are very important in order to planning socio-sanitary programs that aim to increase therapeutic adherence.

Socioeconomic status and access to multiple sclerosis treatment in Mexico.

INTRODUCTION: Multiple sclerosis (MS) is a chronic neurological autoimmune condition and the leading non-traumatic cause of neurological disability worldwide. Disease-modifying therapies (DMT) directly impact on the long-term prognosis of patients with MS preventing relapses and the associated disability progression. Here, we analyzed the impact of socioeconomic status (SES) on DMT access in Mexican patients. METHODS: We evaluated the association between SES and DMT access using the MS registry from the National Institute of Neurology and Neurosurgery in Mexico City. We included 974 patients with MS (McDonald 2010 criteria). We categorized SES according to the 2018 Mexican Association of Market Research Agencies (AMAI) SES classification. We analyzed DMT type, MS phenotype, educational level, symptomatic onset to diagnosis, EDSS at arrival, as well as the progression index. Chi-squared and Wilcoxon tests were used, and multivariable analysis performed for DMT access. RESULTS: When comparing the lower versus higher levels of SES, a significant association was found on the percentage of patients with higher levels of disability (EDSS >6) at arrival, the proportion of patients not receiving any DMT and a higher proportion of secondary progressive MS (p=0.006, p<0.001and p=0.004, respectively). We also found that lower educational levels had a significance and inverse association with EDSS on first visit (p=0.019), symptomatic onset to diagnosis (p<0.001) and a higher disability status at arrival (EDSS >6, p=0.010). CONCLUSIONS: Our study suggests that SES is an important factor determining not only prompt but overall access to highly effective DMT. Lower SES are associated with greater levels of disability at the first clinic visit and a higher proportion of patients not receiving DMT up to 12 months of follow-up.

Interferon beta 1a (Rebif®) in relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that affects the central nervous system. It is the second cause of neurological disability in young adults. The exact cause of the disease remains unknown and there is no curative treatment. It is imperative to evaluate the efficacy of newest, biotechnological products modifying the disease. This study was designed to evaluate the use of interferon beta 1a (Rebif®) in patients with relapsing remitting MS treated at International Center for Neurological Restoration. Thirty-one patients with relapsing remitting MS, between 10 and 65 years of age, four males and 27 females, were treated with Rebif® three times per week during 1 year. The safety of the treatment was evaluated based on the adverse events and the efficacy based on the disability scale score, the number of attacks and the number of lesions at magnetic resonance imaging (MRI). The public clinical trial is registered in Cuba (Number B-10-030-L03). Adverse effects occurred in 75% of the cases, but they were mild. A significant reduction in the number of attacks, the disability scale score and the number of lesions at MRI were observed in patients with relapsing remitting MS treated with Rebif®. The use of interferon beta 1a showed safety and efficacy in the treatment of patients with relapsing remitting MS.

Multiple sclerosis and related disorders: Short report peripheral vascular events in a real-world cohort of multiple sclerosis patients using Fingolimod.

BACKGROUND: Fingolimod is a high-efficacy disease-modifying therapy for multiple sclerosis (MS) and was the first oral treatment approved for the disease. Adverse events include bradyarrhythmia, hypertension, macular oedema and increased risk of infections, mainly due to its main mechanism of action, the non-selective modulation of sphingosine-1-phosphate receptor. METHODS AND RESULTS: We report the baseline characteristics, effectiveness outcomes and adverse events of a prospective cohort of 177 patients with a median treatment duration of 24 months, in which four patients (2.3%) presented with otherwise non-provoked peripheral vascular events (PVE). CONCLUSIONS: Further studies are still needed to evaluate the frequency and severity of PVE in fingolimod patients.