Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).

Study Overview
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Brief Summary
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The aim of this study is to identify whether it is possible to safely discontinue treatment in relapsing-onset MS patients who have shown no evidence of active inflammation in the years prior to inclusion clinically and/or radiologically. The secondary objectives address the questions whether the discontinuation of first-line treatment has an effect on disability progression and whether the discontinuation of first-line treatment improves the quality of life for the patient. Furthermore, blood collections will be included to assess whether it is possible to retrospectively predict possible return of inflammatory activity with biomarkers such as neurofilament light (NFL) or patient characteristics such as disease activity prior to disease modifying therapy (DMT). In case of emerging disease activity after the cessation of therapy we will assess if reinitiation will lead to NEDA again, and if there are long-term consequences. If possible, post-hoc analysis are performed for the different types of treatment compounds.

Official Title
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The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.

Conditions
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Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive

Intervention / Treatment
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* Drug: DMT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum age of 18 years Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations. Definite diagnosis of relapsing-onset MS according to the revised McDonald 2017 criteria Treatment with one of the first-line DMTs: any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide Complete absence of inflammatory activity (no objectively defined and confirmed relapses, no significant number (2 or more) of new-T2 lesions and no contrast-enhancing lesions) for 5 consecutive years under first-line treatment Exclusion Criteria: A switch between first-line disease modifying therapy over two years prior to inclusion, in case the switch has been due to in effectivity of the first DMT. Women who want to discontinue medication because of a pregnancy wish and women who are pregnant or expect to become pregnant during the study period Patients that have previously used interferon-beta and have been tested positive for neutralizing antibodies (NAbs).

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Discontinuation of DMT<br>Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) | Drug: DMT<br>* Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)<br>* Other names: Teriflunomide;|
| No Intervention: Continuation of DMT<br>Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical relapses | New clinically confirmed relapses (defined according to the definition most often used in MS phase-III trials: the onset of new or recurrent symptoms that last > 24 hours, that are accompanied by new objective abnormalities on a neurological examination and that are not explained by non-MS processes such as fever, infection, severe stress or drug toxicity). | 2 years | 
| New lesions on MRI-brain | New inflammatory disease activity on MRI (defined as 3 or more lesions on T2-weighted vimages or 2 or more gadolinium enhancing lesions on T1-weighted post-contrast MRI). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDSS (Expanded Disability Status Scale) | This score indicates disability on a scale of 0 to 10. A higher score indicates more disability. | 2 years | 
| 9-hole peg test | 9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function. | 2 years | 
| Timed 25-Foot Walk | Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function. | 2 years | 
| Symbol Digits Modalities Test | Symbol Digits Modalities Test (SDMT): measures cognition. Scored with a number from 0 to 110, a higher score indicates better cognitive function. | 2 years | 
| MRI-parameter: T1 post-contrast lesion number | Number of lesions on T1 post-contrast MRI | 2 years | 
| MRI-parameter: T2 post-contrast lesion number | Number of lesions on T2-MRI | 2 years | 
| Multiple Sclerosis Impact Scale (MSIS-29) | Questionnaire on the impact of MS on day-to-day life | 2 years | 
| Short Form health survey (SF-36) | Questionnaire on general health | 2 years | 
| Checklist Individual Strength (CIS20r) | Questionnaire on fatigue | 2 years | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) | Questionnaire on treatment satisfaction | 2 years | 
| EuroQol 5 dimensions questionnaire (EQ-5D-5L) | Questionnaire on quality of life and costs | 2 years | 
| Medical consumption questionnaire (iMCQ) | Questionnaire on medical consumption | 2 years | 
| Productivity costs questionnaire (iPCQ) | Questionnaire on productivity | 2 years | 
| Neurofilament light level in serum | Neurofilament light levels in serum | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, disease modifying therapy