Relapsing Multiple Sclerosis
Conditions
Keywords
Relapsing Multiple Sclerosis, RMS, NIS, ofatumumab
Brief summary
This is an observational, non-interventional, multicenter, open-label study in patients being treated with any approved injectable or selected oral DMT for RMS in Germany. Prospective, primary data will be collected via questionnaires and an electronic case report form (eCRF) over a period of up to four years. Additionally, medical history of participants will be collected including disease duration, laboratory values, EDSS, MRI parameters and relapses.
Detailed description
The prerequisite for participation in this observational study is the independent decision of the treating physician and patient to start an approved injectable or oral DMT for RMS as routine medical treatment. This decision must have been made prior to enrollment in this study. Cohort 1: The prospective observational period per patient in the core part will be up to approx. two years from the time of consent (2 years +2 months visit window). If a patient re-consents to the extension part, then the prospective extension observational period will be additional approx. two years, resulting in a total observational period (prospectively for the core and extension part & retrospectively for the potential gap between core and extension part) of approx. 4 years (+ 2 month visit window). Cohort 2: The prospective observational period per patient will be up to approx. two years from the time of consent (2 years + 2 months visit window). The observational period will not be dictated by the protocol. The follow-up documentation will take place at a frequency defined as per investigator's discretion. The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy and to routine clinical care, can be performed as telemedicine visits and will take place as per investigator's discretion.
Interventions
OTHERofatumumab
There is no treatment allocation. Patients administered ofatumumab by prescription that have started as routine medical treatment will be enrolled.
OTHERglatiramer acetate
There is no treatment allocation. Patients administered glatiramer acetate by prescription that have started as routine medical treatment will be enrolled.
OTHERinterferon β1
There is no treatment allocation. Patients administered interferon β1 by prescription that have started as routine medical treatment will be enrolled.
OTHERteriflunomide
There is no treatment allocation. Patients administered teriflunomide by prescription that have started as routine medical treatment will be enrolled.
There is no treatment allocation. Patients administered dimethyl fumarate (DMF) by prescription that have started as routine medical treatment will be enrolled.
There is no treatment allocation. Patients administered diroximel fumarate (DRF) by prescription that have started as routine medical treatment will be enrolled.
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Cohort 1 Inclusion Criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Male or female patients aged ≥18 years at enrollment 3. Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018b) 4. RMS with active disease as defined by Lublin et al. (2014) 5. Max. 1 relapse during the previous year and max. 2 relapses during the previous two years prior to enrollment 6. Disability status at enrollment with an EDSS score of 0 to 2.5 (inclusive) 7. Planned initiation or initiation within the past 14 days with an approved injectable DMT for MS as routine medical treatment Cohort 2 Inclusion Criteria: 1. Signed informed consent must be obtained prior to participation, 2. Male or female patients aged ≥18 years at enrollment, 3. Diagnosis of MS according to the 2024 revised McDonald criteria (Montalban et al., 2025), 4. RMS with active disease as defined by Lublin et al. (2014) , 5. Max. 1 relapse during the previous year and max. 2 relapses during the previous two years prior to enrollment, 6. Disability status at enrollment with an EDSS score of 0 to 3.0 (inclusive), 7. Planned initiation or initiation within the past 14 days with an approved injectable or oral DMT for MS as routine medical treatment: * Ofatumumab: only naïve patients or patients previously treated with max. one DMT other than ofatumumab * IFN-β1, GA, teriflunomide, DMF or DRF: only naïve patients Cohort 1
Exclusion criteria
1. Patients being treated outside of the approved label 2. \> 5 years since first symptom(s) (leading to MS diagnosis) at enrollment 3. Previous therapy with any DMT for the treatment of MS prior to enrollment (except within the past 14 days with an approved injectable DMT for MS as routine medical treatment; see Inclusion criteria #7) 4. Relapse prior to enrollment which has led to a severe deficit relevant to everyday life upon discretion of the investigator after exhaustion of the relapse therapy 5. Poor recovery from the first two relapses prior to enrollment upon discretion of the investigator 6. EDSS Functional System Score "Pyramidal Functions" ≥ 2 at enrollment 7. Simultaneous participation in any investigational trial or simultaneous participation in another Novartis-sponsored non-interventional study with Ofatumumab Cohort 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who continue to receive their baseline treatment | Month 24 | Proportion of patients who continue to receive their baseline treatment \[ofatumumab or other approved disease modifying therapies (IFN-β1, GA, teriflunomide, DMF or DRF)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who continue to receive their baseline treatment | Month 12 | 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 | From Baseline to event, up to 24 months | Time-to-event analysis for retention time on baseline treatment \[ofatumumab or other approved disease modifying therapies (IFN-β1, GA, teriflunomide, DMF or DRF)\] |
| Impact of first-line treatment on health economy | Baseline, month 6, month 12, month 18 and month 24 | 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 | Baseline, month 3, month 6, month 12, month 18, month 24 | 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. |
| Patient Health Questionnaire 8 [PHQ-8] | Baseline, month 3, month 6, month 12, month 18, month 24 | 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. |
| Generalized Anxiety Disorder Scale 7 [GAD-7] | Baseline, month 3, month 6, month 12, month 18, month 24 | 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 |
| Multiple Sclerosis Impact Scale 29 v2 | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24 | 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). |
| Quality of Life in Neurological Disorders [NeuroQoL] | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24 | 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] | Baseline, month 3, month 6, month 12, month 18, month 24 | 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. |
| Expanded disability status scale (EDSS) | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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) | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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) | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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) | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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 | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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 | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | T1 Gd-enhancing lesions per brain to be measured |
| Annualized T2 lesion rate | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | New or enlarging T2 lesions per brain and per year (annualized T2 lesion rate) |
| Presence of spinal cord lesions | Baseline, month 3,month 6, month 9, month 12, month 15, month 18, month 21, month24 | Proportion of patients with spinal cord lesions present |
| Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator. | Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 | 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 and no discontinuation of current treatment due to AEs | Up to 24 months | 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 | Up to 24 months | 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. |
| Time to first relapse | Up to 24 months | 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. |
| Proportion of relapse free patients | Up to 24 months | 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. |
| Serum NfL levels | Baseline, month 6, month 12, month 18 and month 24 | sNfL levels |
| Proportion of patients with low or elevated sNfL levels | Baseline, month 6, month 12, month 18 and month 24 | Proportion of patients with low or elevated sNfL levels |
| Association of selected effectiveness and PRO outcomes with sNfL levels | Baseline, month 6, month 12, month 18 and month 24 | Association of higher or lower sNfL concentrations with differences in e.g. disease activity, functional status, quality of life, and other PRO-based measures |
| Reasons for treatment decisions | Up to 24 months | Number of participants by reasons for treatment decisions |
| Number of patients and reasons for discontinuation of treatment | Up to 24 months | 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 continue to receive their subsequent treatment | Up to 24 months | 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 | Up to 24 months | Reasons for and number of treatment interruptions per patient to be collected |
| Duration of treatment interruptions per patient | Up to 24 months | Duration of treatment interruptions per patient to be collected |
| Number of patients with treatment interruptions | Up to 24 months | Number of patients with treatment interruptions to be collected |
| Proportion of drug-related adverse events (AEs) | Up to 24 months | 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) | Up to 24 months | 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 | Up to 24 months | 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 | Up to 24 months | 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 | Baseline, month 6, month 12, month 18 and month 24 | Proportion of sites that share the standardized MRI report form with their radiological colleagues |
| Proportion of standardized MRI report forms and conventional radiologists' reports | Baseline, month 6, month 12, month 18 and month 24 | Proportion of standardized MRI report forms and conventional radiologists' reports |
| Effect of standardized MRI report form on completeness of lesion documentation | Baseline, month 6, month 12,1 month 8 and month 24 | Proportion of complete MRI lesion documentation using the standardized MRI form versus non-standardized documentation. |
| Physician's view on added value of standardized MRI report form over conventional radiologists' reports | Baseline, month 6, month 12, month 18 and month 24 | 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 | Month 6,month 12, month 18 and month 24 | 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 | Month 6,month 12, month 18 and month 24 | Proportion of patients that access their PRO and sNfL result visualizations at least once every 6 months |
| Perceived value of PRO and sNfL result visualizations from the perspective of both patient and treating physician on patient-physician dialogue and shared decision making | Month 6,month 12, month 18 and month 24 | 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 of male and female participants | Baseline | Age |
| Number of previous MS relapses of male and female participants | Baseline | Number of MS relapses in the 24 months prior baseline |
| Serum NfL levels of male and female patients | Baseline, month 6, month 12, month 18 and month 24 | sNfL levels |
| Proportion of male and female patients who continue to receive their baseline treatment | Month 12, Month 24 | 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 of male and female patients | Up to 24 months | Annualized relapse rate, defined as the number of confirmed Multiple Sclerosis relapses in a year of male and female participants |
| Reasons for treatment decisions of male and female patients | Up to 24 months | Number of male and female participants by reasons for treatment decisions |
| Quality of Life in Neurological Disorders [NeuroQoL] of male and female patients | Baseline, month 3, month 6, month 9, month 12, month15, month 18, month 21 and month 24 | 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 |
Countries
Germany
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed