Clinical trial NCT04260711: Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).
Official title: The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Secondary Progressive
Keywords: multiple sclerosis
disease modifying therapy
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2020-02-07
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Clinical relapses
timeFrame: 2 years
measure: New lesions on MRI-brain
timeFrame: 2 years
Secondary outcomes:
measure: EDSS (Expanded Disability Status Scale)
timeFrame: 2 years
measure: 9-hole peg test
timeFrame: 2 years
measure: Timed 25-Foot Walk
timeFrame: 2 years
measure: Symbol Digits Modalities Test
timeFrame: 2 years
measure: MRI-parameter: T1 post-contrast lesion number
timeFrame: 2 years
measure: MRI-parameter: T2 post-contrast lesion number
timeFrame: 2 years
measure: Multiple Sclerosis Impact Scale (MSIS-29)
timeFrame: 2 years
measure: Short Form health survey (SF-36)
timeFrame: 2 years
measure: Checklist Individual Strength (CIS20r)
timeFrame: 2 years
measure: Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: 2 years
measure: EuroQol 5 dimensions questionnaire (EQ-5D-5L)
timeFrame: 2 years
measure: Medical consumption questionnaire (iMCQ)
timeFrame: 2 years
measure: Productivity costs questionnaire (iPCQ)
timeFrame: 2 years
measure: Neurofilament light level in serum
timeFrame: 2 years
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: J. Killestein, prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: