The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.
Overview
- Phase
- Not Applicable
- Intervention
- DMT
- Conditions
- Multiple Sclerosis
- Sponsor
- Amsterdam UMC, location VUmc
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- Clinical relapses
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eline Coerver
Corresponding investigator, (also: E.M.M. Strijbis (coordinating investigator) and J. Killestein (principal investigator))
Amsterdam UMC, location VUmc
Eligibility Criteria
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).
Arms & Interventions
Discontinuation of DMT
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Intervention: DMT
Outcomes
Primary Outcomes
Clinical relapses
Time Frame: 2 years
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).
New lesions on MRI-brain
Time Frame: 2 years
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).
Secondary Outcomes
- EDSS (Expanded Disability Status Scale)(2 years)
- 9-hole peg test(2 years)
- Timed 25-Foot Walk(2 years)
- Symbol Digits Modalities Test(2 years)
- MRI-parameter: T1 post-contrast lesion number(2 years)
- MRI-parameter: T2 post-contrast lesion number(2 years)
- Multiple Sclerosis Impact Scale (MSIS-29)(2 years)
- Short Form health survey (SF-36)(2 years)
- Checklist Individual Strength (CIS20r)(2 years)
- Treatment Satisfaction Questionnaire for Medication (TSQM)(2 years)
- EuroQol 5 dimensions questionnaire (EQ-5D-5L)(2 years)
- Medical consumption questionnaire (iMCQ)(2 years)
- Productivity costs questionnaire (iPCQ)(2 years)
- Neurofilament light level in serum(2 years)