No registrations found.
ID
Source
Brief title
Health condition
Multiple Sclerosis
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is number of patients with return of inflammatory disease activity after 2 years based on: a clinically confirmed relapse (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 (Gold et al NEJM 2012)) , or any emerging subclinical disease activity proven to be due to active disease/new inflammation (defined as 3 or more lesions on T2—weighted images or 2 or more gadolinium enhancing lesions on T1-weighted post-contrast MRI) in the discontinuation group.
Secondary outcome
Secondary end points are:
- Changes in neurological functioning (EDSS, MSFC)
- Individual MRI-parameters (T1-post contrast lesion numbers and volumes, T2-lesion numbers and volumes, atrophy measurements)
Background summary
The aim of this study is to identify whether it is possible to safely discontinue treatment in 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 objective
Discontinuation of first-line disease modifying medication (DMT) in patients with relapsing-onset multiple sclerosis that are inflammatory stable for at least 5 years, can be safely done without the return of inflammatory activity.
Study design
Data collection at the end of the trial, interim analysis
Intervention
Discontinuation of disease-modifying treatment
Inclusion criteria
1. A minimum age of 18 years
2. 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.
3. Definite diagnosis of relapsing-onset MS according to the revised McDonald 2017 criteria
4. All relapsing-onset MS patients treated with one of the first-line treatments: any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide
5. 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
1. 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. In case the switch has been due to side-effects or by a personal preference of the patient (such as the wish to switch to oral therapies), this is not considered as an exclusion criterium.
2. 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
3. Patients that have previously used interferon-beta and have been tested positive for neutralizing antibodies (NAbs). This is determined by measuring MxA-bioactivity and is a test that is part of routine follow-up in patients that use interferon-beta. The reason for this is that development of NAbs has been shown to affect interferon-beta treatment efficacy.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8188 |
| Other | METC VUmc : METc VUmc 2019.662 |