Advances in the Diagnosis and Treatment of Multiple System Atrophy / 罕见病研究

Multiple system atrophy (MSA) is a rare and rapidly-progressive neurodegenerative disorder, characterized by the combination of dysautonomia, poor levodopa responsive parkinsonism, cerebellar ataxia, and pyramidal tract signs. Insidious onset, clinical heterogeneity and progression of the disease complicate the difficulty of early diagnosis and challenge, the development of neuroprotective drugs. In order to improve the knowledge of diagnosis and treatment of the disease, this paper reviews advances in its diagnostic criteria, biomarkers of early diagnosis and management of the disease.

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.

Treatment patterns of patients with multiple sclerosis in Guangzhou, China

@#Background & Objective: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are widely used in Western countries. In China, however, the current treatment patterns of MS patients are not well characterized. This is to explore the gap between the current treatments in Guangzhou, Southern China and those given in Western countries. Methods: We performed a survey of MS patients at department of neurology, a tertiary MS referral centre in Guangzhou, concerning treatments of MS in Southern China. The clinical data in patients were collected. The initial treatment, drug withdrawal or switching profile, and therapeutic effect of existing treatments in MS patients were analyzed. Results: The ratio of MS patients who receive DMTs in Guangzhou China is extremely low. Among the 178 patients studied, only 28.09% received initial treatment with DMTs. MS patients who receive initial treatment with first-line DMTs have higher drug withdrawal rates (32.6%) and drug switching rates (30.43%) than those of western populations. The main reasons for withdrawal of first-line DMTs were doctor’s advice (maintenance of remission) (40.00%), economic burden(20.00%), and no channels to buy drugs(13.33%). In MS patients initially treated with first-line DMTs who switched to other drugs, a gap between treatments was common (8/14;57.14%). There were 18 patients with highly active MS receiving treatment with rituximab. Annual relapse rate after treatment significantly decreased than that before treatment (0.74 vs. 1.50 , P < 0.001). Conclusions: DMTs for MS in Guangzhou, Southern China appear to lag behind those in Western countries. Much work is needed to improve drug accessibility and affordability of DMTs in China. Rituximab is an option for highly active MS in limited medical-resource countries.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p < 0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

Recent Update of Clinical Drug Trials in Alzheimer's Disease

The prevalence of Alzheimer's disease (AD) is increasing as the global population ages. Currently available treatments for AD target cholinergic and glutamatergic neurotransmission. There have been modest symptomatic effects, but disease modifying effects have not been accomplished. This is even true of clinical trials of bapineuzumab and solanezumab, two humanized monoclonal antibodies that bind amyloid. Therefore, innovations in clinical trial designs are necessary, including revised diagnostic criteria and treatment at the earliest stages of AD. Several prevention trials started in 2013, emphasizing these innovative principles of clinical trial design. In this review, we will discuss the paradigm shift for AD clinical treatment trials and ongoing preventative trials.