A NIS Evaluating Various Injectable and Oral Treatments in Patients With Relapsing Multiple Sclerosis

Proportion of patients who continue to receive their baseline treatment [ofatumumab or other approved disease modifying therapies (IFN-β1, GA, teriflunomide, DMF or DRF)]

Time-to-event analysis for retention time on baseline treatment [ofatumumab or other approved disease modifying therapies (IFN-β1, GA, teriflunomide, DMF or DRF)]

Mean annual health care resource utilization cost, annual direct medical costs, annual direct nonmedical costs and annual indirect costs as measured by MS Health Resource Utilization Survey [MS-HRS]

MS-HRS is a 24-item questionnaire covers societal resource use, regardless of the issue of reimbursement, as well as impact of the disease on work, family and leisure. With the help of this questionnaire a monetary value can be assigned to e.g. the stage of MS, a relapse or a therapy.

Fatigue Symptoms and Impact Questionnaire-RMS [FSIQ-RMS]

The FSIQ-RMS comprises 20 items organized in a conceptual framework with 2 symptom domains (energy, muscle weakness) and 7 impact domains (daily activities, cognition, emotions, physical impact, self-care, sleep, social impact) in order to measure fatigue symptoms and impacts in relapsing multiple sclerosis.

A scoring algorithm standardizes scores on both the symptoms domain (daily and weekly) and impacts subdomains (weekly) to a 0 to 100 scale, with higher scores indicating more severe symptoms and impacts. There is no single summary score across the FSIQ-RMS instrument, but rather 1 symptoms score and 3 impacts subdomain scores.

The PHQ-8 is a valid diagnostic and severity measure for depressive disorders. It consists of eight items, each of which is scored 0 to 3, providing a 0 to 24 severity score. Scores of 5, 10, 15, and 20 represent cutpoints for mild, moderate, moderately severe and severe depression, respectively.

The GAD-7 is a validated 7-item anxiety scale to diagnose generalized anxiety disorder. Each of the items is scored 0 to 3, providing a 0 to 21 severity score. Scores of 5, 10, and 15 represent cutpoints for mild, moderate, and severe anxiety, respectively

In this non-interventional study only the nine psychological items will be used to allow conclusions regarding the mental health status of patients with mildly active multiple sclerosis. In its version 2, each item of the MSIS-29 provides four response alternatives, which are rated as 1 to 4. Accordingly, the psychological scale will be described by a raw score between 9 and 36, which will be transformed into a final score between 0 (no impact) and 100 (extreme impact).

n this non-interventional study the following items will be used: Anxiety, Depression, Ability to Participate in Social Roles and Activities, Positive Affect and Well-Being \& Sleep Disturbance. Each response option is assigned a value (e.g.,1=Not at all) and total summed raw score for each respondent are calculated. The total raw score is then translated into a T-score for each participant by using conversion tables. These Tscore are standardized scores with a mean of 50 and a standard deviation (SD) of 10.

MS Treatment Concerns Questionnaire [MSTCQ] is used to assess participants' satisfaction with their treatment injections.

The MSTCQ includes 20 items pertaining satisfaction with the injection system (including issues related to use of the device and preparation of the medication for injection), and AEs related to the patient MS treatment.

All questions have a 5-point response choice, with the responses scored between 1-5. The MSTCQ scores are formed as the sum of all scores. The maximum total score is 100. Lower scores indicate a better state.

EDSS is a widely used and accepted instrument to evaluate disability status at a given time and, longitudinally, to assess accumulation of disability in clinical studies in MS. The EDSS scale consists of scores in each of seven functional systems (FSs) and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral functions (Fatigue contributes)

Time to onset of confirmed disability worsening (CDW) defined as an increase from baseline in EDSS sustained for at least 3 and 6 months, respectively

Proportion of patients with confirmed disability worsening (CDW) defined as an increase from baseline in EDSS sustained for at least 3 and 6 months, respectively

Time to onset of confirmed disability improvement (CDI) defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months

Proportion of patients with CDI defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months

T1 Gd-enhancing lesions per brain to be measured

New or enlarging T2 lesions per brain and per year (annualized T2 lesion rate)

Proportion of patients with spinal cord lesions present

Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator. NEDA3 is defined as no 3mCDP, no confirmed MS relapse and no new or enlarging T2 lesions on any MRI scan compared to baseline

Proportion of patients with no clinical disease activity measured by relapse and disease progression and no discontinuation of current treatment due to AEs (excluding pregnancies) and lack of effectiveness

Annualized relapse rate, defined as the number of confirmed Multiple Sclerosis relapses in a year.

Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (< 37.5°C) or a known infection.

Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (< 37.5°C) or a known infection.

Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (< 37.5°C) or a known infection.

sNfL levels

Proportion of patients with low or elevated sNfL levels

Association of higher or lower sNfL concentrations with differences in e.g. disease activity, functional status, quality of life, and other PRO-based measures

Number of participants by reasons for treatment decisions

Number of patients and reasons for discontinuation of treatment classified by category:

• efficacy (e.g. occurrence of relapse, evidence of disease activity in MRI)
• safety and tolerability (e.g. injection-site reactions, influenza-like symptoms)
• or convenience (e.g. inconvenient administration, frequency of injections)

Proportion of patients who, at a given time over the observational period, continue to receive their subsequent treatment

Reasons for and number of treatment interruptions per patient to be collected

Duration of treatment interruptions per patient to be collected

Number of patients with treatment interruptions to be collected

Proportion of drug-related adverse events (AEs) including those of special interest (main focus on injection site reactions such as scarring, skin reactions)

Persistence of drug-related adverse events (AEs) including those of special interest (main focus on injection site reactions such as scarring, skin reactions, influenza-like symptoms)

Specific safety assessment of injection related AEs. (i.e. injection site reaction AEs vs. injection systemic reaction AEs) summarized by providing the number and percentage of patients with each of the symptoms and pre-specified grouping of symptoms as well as overall.

Proportion of participants discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons

Proportion of sites that share the standardized MRI report form with their radiological colleagues

Proportion of standardized MRI report forms and conventional radiologists' reports

Proportion of complete MRI lesion documentation using the standardized MRI form versus non-standardized documentation.

Proportion of physicians who rate the added value of the standardized MRI report form higher than that of conventional radiologists' reports

Proportion of patients and physicians that intend to view and use PRO and sNfL results to support patient-physician dialogue

Proportion of patients that access their PRO and sNfL result visualizations at least once every 6 months

Proportion of patients and physicians who perceive an added value of PRO and sNfL result visualizations on patient-physician dialogue and shared decision making

Age

Number of MS relapses in the 24 months prior baseline

sNfL levels

Proportion of male and female patients who continue to receive their baseline treatment [ofatumumab or other approved disease modifying therapies (IFN-β1, GA, teriflunomide, DMF or DRF)]

Annualized relapse rate, defined as the number of confirmed Multiple Sclerosis relapses in a year of male and female participants

Number of male and female participants by reasons for treatment decisions

T-scores of male and female patients.

• Anxiety: Score range from 36.4 to 76.8
• Depression: Score range from 36.9 to 75.0
• Sleep Disturbance: Score range from 32.0 to 84.2
• Ability to Participate in Social Roles and Activities: Score range from 24.1 to 60.2
• Positive Affect and Well-Being: Score range from 26.3 to 68.0 For positive domains (e.g. Well-Being): higher score = better QoL. For symptom domains (e.g. Anxiety): higher scores = worse symptoms