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

Keywords

• Relapsing Multiple Sclerosis
• RMS
• NIS
• ofatumumab

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Study population

Eligibility criteria

Groups and cohorts

• Ofatumumab

  Patients treated with ofatumumab

  Other: ofatumumab

• Standard of Care (SoC)

  Patients treated with either interferon β1 (IFN-β1), glatiramer acetate (GA), teriflunomide, dimethyl fumarate (DMF) or diroximel fumarate (DRF)

  Other: glatiramer acetate · Other: interferon β1 · Other: teriflunomide · Other: dimethyl fumarate (DMF) · Other: diroximel fumarate (DRF)

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.

• Otherdimethyl fumarate (DMF)

  There is no treatment allocation. Patients administered dimethyl fumarate (DMF) by prescription that have started as routine medical treatment will be enrolled.

• Otherdiroximel fumarate (DRF)

  There is no treatment allocation. Patients administered diroximel fumarate (DRF) by prescription that have started as routine medical treatment will be enrolled.

Primary outcomes

1. Proportion of patients who continue to receive their baseline treatment

   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 frame: Month 24

Secondary outcomes

1. Proportion of patients who continue to receive their baseline treatment

   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 frame: Month 12

2. Time to event analysis for retention time on baseline treatment

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

   Time frame: From Baseline to event, up to 24 months

3. Impact of first-line treatment on health economy

   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.

   Time frame: Baseline, month 6, month 12, month 18 and month 24

4. Fatigue Symptoms and Impact Questionnaire-RMS

   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.

   Time frame: Baseline, month 3, month 6, month 12, month 18, month 24

5. Patient Health Questionnaire 8 [PHQ-8]

   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.

   Time frame: Baseline, month 3, month 6, month 12, month 18, month 24

6. Generalized Anxiety Disorder Scale 7 [GAD-7]

   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

   Time frame: Baseline, month 3, month 6, month 12, month 18, month 24

7. Multiple Sclerosis Impact Scale 29 v2

   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).

   Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24

8. Quality of Life in Neurological Disorders [NeuroQoL]

   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.

   Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24

9. MS Treatment Concerns Questionnaire [MSTCQ]

   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.

   Time frame: Baseline, month 3, month 6, month 12, month 18, month 24

10. Expanded disability status scale (EDSS)

    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 frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

11. Time to onset of confirmed disability worsening (CDW)

    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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

12. Proportion of patients with confirmed disability worsening (CDW)

    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 frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

13. Time to onset of confirmed disability improvement (CDI)

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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

14. Proportion of patients with CDI

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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

15. T1 Gd-enhancing lesions per brain

    T1 Gd-enhancing lesions per brain to be measured

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

16. Annualized T2 lesion rate

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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

17. Presence of spinal cord lesions

    Proportion of patients with spinal cord lesions present

    Time frame: Baseline, month 3,month 6, month 9, month 12, month 15, month 18, month 21, month24

18. Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator.

    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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

19. Proportion of patients with no clinical disease activity and no discontinuation of current treatment due to AEs

    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

    Time frame: Up to 24 months

20. Annualized relapse rate

    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 frame: Up to 24 months

21. Time to first relapse

    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 frame: Up to 24 months

22. Proportion of relapse free patients

    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 frame: Up to 24 months

23. Serum NfL levels

    sNfL levels

    Time frame: Baseline, month 6, month 12, month 18 and month 24

24. Proportion of patients with low or elevated sNfL levels

    Proportion of patients with low or elevated sNfL levels

    Time frame: Baseline, month 6, month 12, month 18 and month 24

25. Association of selected effectiveness and PRO outcomes with 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

    Time frame: Baseline, month 6, month 12, month 18 and month 24

26. Reasons for treatment decisions

    Number of participants by reasons for treatment decisions

    Time frame: Up to 24 months

27. Number of patients and reasons for discontinuation of treatment

    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)

    Time frame: Up to 24 months

28. Proportion of patients who continue to receive their subsequent treatment

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

    Time frame: Up to 24 months

29. Reasons for and number of treatment interruptions per patient

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

    Time frame: Up to 24 months

30. Duration of treatment interruptions per patient

    Duration of treatment interruptions per patient to be collected

    Time frame: Up to 24 months

31. Number of patients with treatment interruptions

    Number of patients with treatment interruptions to be collected

    Time frame: Up to 24 months

32. Proportion of drug-related adverse events (AEs)

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

    Time frame: Up to 24 months

33. Persistence of drug-related adverse events (AEs)

    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)

    Time frame: Up to 24 months

34. Specific safety assessment of injection related AEs

    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.

    Time frame: Up to 24 months

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

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

    Time frame: Up to 24 months

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

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

    Time frame: Baseline, month 6, month 12, month 18 and month 24

37. Proportion of standardized MRI report forms and conventional radiologists' reports

    Proportion of standardized MRI report forms and conventional radiologists' reports

    Time frame: Baseline, month 6, month 12, month 18 and month 24

38. Effect of standardized MRI report form on completeness of lesion documentation

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

    Time frame: Baseline, month 6, month 12,1 month 8 and month 24

39. Physician's view on added value of standardized MRI report form over conventional radiologists' reports

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

    Time frame: Baseline, month 6, month 12, month 18 and month 24

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

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

    Time frame: Month 6,month 12, month 18 and month 24

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

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

    Time frame: Month 6,month 12, month 18 and month 24

42. 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

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

    Time frame: Month 6,month 12, month 18 and month 24

43. Age of male and female participants

    Age

    Time frame: Baseline

44. Number of previous MS relapses of male and female participants

    Number of MS relapses in the 24 months prior baseline

    Time frame: Baseline

45. Serum NfL levels of male and female patients

    sNfL levels

    Time frame: Baseline, month 6, month 12, month 18 and month 24

46. Proportion of male and female patients who continue to receive their baseline treatment

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

    Time frame: Month 12, Month 24

47. Annualized relapse rate of male and female patients

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

    Time frame: Up to 24 months

48. Reasons for treatment decisions of male and female patients

    Number of male and female participants by reasons for treatment decisions

    Time frame: Up to 24 months

49. Quality of Life in Neurological Disorders [NeuroQoL] of male and female patients

    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

    Time frame: Baseline, month 3, month 6, month 9, month 12, month15, month 18, month 21 and month 24

Individual participant data

Plan to share: No