Dimethyl Fumarate (DMF) Observational Study

Study Overview
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Brief Summary
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The primary objective of the study is to determine the incidence, type, and pattern of serious adverse events (SAEs), including but not limited to infections (including opportunistic infections), hepatic events, malignancies, and renal events, and of adverse events (AEs) leading to treatment discontinuation in patients with MS treated with dimethyl fumarate (DMF). Secondary objectives of this study in this population are as follows: To determine dimethyl fumarate (DMF) prescription and utilization patterns in routine clinical practice in patients with multiple sclerosis (MS); To assess the effectiveness of dimethyl fumarate (DMF) on multiple sclerosis (MS) disease activity and disability progression in routine clinical practice as determined by the Expanded Disability Status Scale (EDSS) score and multiple sclerosis (MS) relapse information; and To assess the effect of dimethyl fumarate (DMF) on health-related quality of life, healthcare resource consumption, and work productivity.

Detailed Description
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Patients aged 12 to under 18 may be included where enrollment of pediatric patients in this study is considered observational and is permissible by local regulations.

Official Title
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A Multicenter, Global, Observational Study to Collect Information on Safety and to Document the Drug Utilization of Tecfidera™ (Dimethyl Fumarate) When Used in Routine Medical Practice in the Treatment of Multiple Sclerosis (ESTEEM)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: dimethyl fumarate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: - Patients with multiple sclerosis (MS) who are newly initiating treatment with dimethyl fumarate (DMF) under routine clinical care are eligible to participate in the study. Key Exclusion Criteria: Patients with previous exposure to dimethyl fumarate (DMF), Fumaderm (fumaric acid esters), or compounded fumarates. Patients participating in other clinical studies. NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| dimethyl fumarate (DMF)<br>Patients with multiple sclerosis receiving dimethyl fumarate (DMF) under routine clinical care | Drug: dimethyl fumarate<br>* Provided under routine clinical care<br>* Other names: BG00012;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants that experience Adverse Events (AEs) that lead to discontinuation of dimethyl fumarate (DMF) |  | Up to 5 years | 
| The number of participants that experience Serious Adverse Events (SAEs) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of dimethyl fumarate (DMF) use |  | Up to 5 years | 
| dimethyl fumarate (DMF) dosing frequency |  | Up to 5 years | 
| Primary reasons for discontinuation of dimethyl fumarate (DMF) use |  | Up to 5 years | 
| Frequency of relapses over time |  | Up to 5 years | 
| Disease progression as measured by Expanded Disability Status Scale (EDSS) over time | The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Participants with confirmed progression of disability in EDSS physical functional system scores will be defined as those who meet one of the following criteria: an increase of ≥ 1 point from baseline system score of ≥ 1 or an increase of ≥ 2 points from baseline system score of 0 in at least 2 physical functional systems, or an increase of ≥ 2 points from baseline system score of ≥ 1 or an increase of ≥ 3 points from baseline system score of 0 in any 1 physical functional system. Worsening must be confirmed on a subsequent examination using the same criterion in the same functional system(s) at least 6 months later. | Up to 5 years | 
| Multiple Sclerosis Impact Scale-29 Items (MSIS-29) physical multiple sclerosis (MS) impact score | The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. | Up to 5 years | 
| Multiple Sclerosis Impact Scale-29 Items (MSIS-29) psychological multiple sclerosis (MS) impact score | The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. | Up to 5 years | 
| EuroQol-5 Dimensions (5 Level) (EQ-5D-5L) index score | Descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension. | Up to 5 years | 
| EuroQol Visual Analogue Scale (EQ VAS) (0-100 scale) | Standard vertical 20 cm visual analogue scale (similar to a thermometer) for recording an individual's rating for their current health-related quality of life state (often referred to as page 3 of the EQ-5D questionnaire) | Up to 5 years | 
| Modified Fatigue Impact Scale-5 (MFIS-5) total score | MFIS-5 is a modified form of the Fatigue Impact Scale that consists of five questions that assess the impact of fatigue on physical, cognitive, and psychosocial functioning, with five response levels ranging from 0 (Never) to 4 (Almost always). Total scores range from 0 to 20, with higher scores representing a greater impact of fatigue. | Up to 5 years | 
| Work Productivity and Activity Impairment questionnaire: Multiple Sclerosis, Version 2.0 (WPAI-MS) impairment percentages | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. | Up to 5 years | 
| Health Care Resource Consumption Questionnaire | The Health Care Resource Consumption questionnaire is a survey that asks patients how MS affects their use of healthcare services and the impact it has on particular areas of their life (including number of hospitalizations [MS-related, non-MS related, relapse-related, resulting in steroid use], MS-related emergency room visits, MS-related neurologist visits, visits to other health care professionals for MS-related and other reasons). | Up to 5 years |