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

点击翻译按钮获取中文摘要

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.