Factors associated with disease-modifying drug-related Safety and Effectiveness in Multiple Sclerosis Patients.

多发性硬化（MS）是一种免疫介导的中枢神经系统（CNS）炎症性疾病。全世界约有250万人患有此病。这是年轻人神经功能障碍的常见原因。它要么是复发的，要么是渐进的。这种疾病很可能是遗传、环境和免疫因素复杂相互作用的结果，这些因素决定了个体的易感性。在过去的25年里，临床药物发展取得了令人满意的成功，现在有一系列可注射、口服和输注的疾病缓解药物（DMD）。本研究项目的目的是识别和评估与dmd相关的安全性、有效性和多发性硬化症患者在个人健康轨迹中的病程相关的因素。对于该项目，将分析1996年至2017年期间从加拿大不列颠哥伦比亚省前瞻性收集的相关卫生行政和ms特定临床数据。目的1 -安全性分析年龄、性别、病程（即复发与进展）和相关的慢性合并症（即哮喘、慢性阻塞性肺病、慢性酒精滥用、慢性尼古丁滥用）等健康相关因素是否与一线和二线DMD暴露患者发生后续感染的风险增加相关。一线治疗被定义为暴露于醋酸格拉替默、β -干扰素、特立氟米特或富马酸二甲酯，二线治疗被定义为暴露于芬戈莫德、那他单抗、利妥昔单抗和阿仑单抗。目的2 -有效性分析复发性感染（即使用国际疾病和相关健康问题统计分类（ICD 9/10）系统在卫生行政数据中编码的活动性感染）和上述相关的慢性合并症是否与一线或二线DMD暴露患者较高的复发率和疾病进展相关。目标3 -地理背景分析地理模式（例如城市与农村、地理背景/原产国）是否影响感染率、复发率和/或疾病进展。居住在温哥华和萨里的患者将被定义为生活在城市地区，所有其他患者将被定义为生活在农村地区。多发性硬化症dmd价格昂贵，可能存在巨大风险，并且已知仅在短期内（通过2 - 3年的临床试验）对部分多发性硬化症患者有益。然而，长期随机临床试验既不可行也不符合伦理。临床和管理数据提供了一个机会来解决这些问题，并探索在现实世界中比较安全性和有效性。

Multiple sclerosis (MS) is an immune-mediated, inflammatory disease of the central nervous system (CNS). Worldwide some 2.5 million people are afflicted. It is a common cause of neurological disability in young adults. It takes either a relapsing or progressive course. The disease most likely results from a complex interplay of genetic, environmental and immunological factors that determine individual susceptibility. The past 25 years have witnessed gratifyingly successful clinical drug developments so that a range of injectable, oral and infusion administered disease-modifying drugs (DMD) are now available. The objective of this research project is to identify and evaluate factors associated with DMD-related safety, effectiveness and disease course in multiple sclerosis patients throughout individual healthcare trajectories.For this project, the linked health administrative and MS-specific clinical data from British Columbia, Canada, which has been prospectively captured from 1996 to 2017 will be analysed. Aim 1 – SafetyTo analyse if health-related factors such as age, sex, disease course (i.e. relapsing versus progressive course) and relevant, chronic comorbidities (i.e. asthma, chronic obstructive pulmonary disease, chronic alcohol abuse, chronic nicotine abuse) are associated with an increased risk of developing subsequent infections in patients under first and second line DMD exposure. First line treatment is defined as exposure to glatiramer acetate, beta-interferon, teriflunomide, or dimethyl fumarate, and second line treatment is defined as exposure to fingolimod, natalizumab, rituximab and alemtuzumab.Aim 2 – EffectivenessTo analyse if recurrent infections [i.e. active infections coded in health administrative data using the International Statistical Classification of Diseases and Related Health Problems (ICD 9/10) system] and relevant, chronic comorbidities as mentioned above are associated with a higher relapse rate and disease progression in patients under first or second line DMD exposure. Aim 3 – Geographical BackgroundTo analyse if geographical patterns (e.g. urban versus rural, geographical background/country of origin) influence the infection rate, relapse rate and/or disease progression. Patients living in Vancouver and Surrey will be defined as living in an urban area, all other patients will be defined as living in a rural area.MS DMDs are costly, may carry substantial risk and are known to benefit subsets of MS patients over the short term only (via 2‐3 year clinical trials). However, long‐term randomized clinical trials are neither feasible nor ethical. Clinical and administrative data provide an opportunity to address these issues and explore comparative safety and effectiveness in the real-world setting.