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

Amsterdam UMC, location VUmc130 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

130

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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).

Time frame: 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).

Time frame: 2 years

Secondary Outcomes

EDSS (Expanded Disability Status Scale)

This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.

Time frame: 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.

Time frame: 2 years

Timed 25-Foot Walk

Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.

Time frame: 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.

Time frame: 2 years

MRI-parameter: T1 post-contrast lesion number

Number of lesions on T1 post-contrast MRI

Time frame: 2 years

MRI-parameter: T2 post-contrast lesion number

Number of lesions on T2-MRI

Time frame: 2 years

Multiple Sclerosis Impact Scale (MSIS-29)

Questionnaire on the impact of MS on day-to-day life

Time frame: 2 years

Short Form health survey (SF-36)

Questionnaire on general health

Time frame: 2 years

Checklist Individual Strength (CIS20r)

Questionnaire on fatigue

Time frame: 2 years

Treatment Satisfaction Questionnaire for Medication (TSQM)

Questionnaire on treatment satisfaction

Time frame: 2 years

EuroQol 5 dimensions questionnaire (EQ-5D-5L)

Questionnaire on quality of life and costs

Time frame: 2 years

Medical consumption questionnaire (iMCQ)

Questionnaire on medical consumption

Time frame: 2 years

Productivity costs questionnaire (iPCQ)

Questionnaire on productivity

Time frame: 2 years

Neurofilament light level in serum

Neurofilament light levels in serum

Time frame: 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts