Silent Progression Activity Monitoring - SPAM Study
Study Details
Study Description
Brief Summary
Real-World Data (RWD) exploring the natural history of MS suggested that relapses do not significantly influence the progression of irreversible disability. Disability progression independent of relapses activity (PIRA) has been confirmed as a frequent relapsing-remitting multiple sclerosis (RRMS) phenomenon based on Randomized Clinical Trials (RCT). Recently, RWD demonstrated that the absence of markers of inflammation (No Evidence of Disease Activity (NEDA) at 2 years did not predict long-term stability. Silent progression has been proposed to describe the insidious disability that accrues many patients who satisfy traditional criteria for relapsing-remitting MS. In this study, the investigators would like to evaluate the occurrence of the SPMS in a population of RRMS patient with an Highly Active Treatment (HAT).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients Patients with RRMS (2017 Mc Donald criteria) treated with highly active treatment in the first 5 years of symptoms onset, at least 1 year, with an EDSS below 4 |
Other: NO INTERVENTION
NO INTERVENTION
|
Outcome Measures
Primary Outcome Measures
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Age in years
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Disease duration (which should be <5 years) in months
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Expanded Disability Status Scale (EDSS) (which must be <4)
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
new T2 lesion(s) on brain MRI and spinal cord MRI (if available)
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
gadolinium enhancement on brain MRI and spinal cord MRI (if available)
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Interval time between the first and the second relapse in months
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Reason for HAT: naive, or switch
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
Number of relapses since MS onset
- Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
DMT administered since MS onset: number of DMT and type
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
More than 9 T2 lesions on MRI
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
At least 1 periventicular T2 lesion on MRI
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
At least 3 periventicular T2 lesions on MRI
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
At least 1 infratentorial T2 lesion on MRI
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
At least 1 spinal cord T2 lesion on MRI
- Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment. [Baseline: beginning of highly active treatment]
At least 1 gadolinium enhancement T1 lesion on MRI
Secondary Outcome Measures
- To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Age in years
- To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Disease duration (which should be <5 years) in months
- To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
EDSS (which must be <4) +/- 3 months
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
new T2 lesion(s) on brain MRI and spinal cord MRI (if available)
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
gadolinium enhancement on brain MRI and spinal cord MRI (if available)
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Interval time between the first and the second relapse in months
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Number of relapses since MS onset
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Number of relapse before baseline
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
Disease Modifying Therapies (DMT) administered since MS onset
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
More than 9 T2 lesions on MRI
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
At least 1 periventicular T2 lesion on MRI
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
At least 3 periventicular T2 lesion on MRI
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
At least 1 infratentorial T2 lesion on MRI
- To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
At least 1 spinal cord T2 lesion on MRI
- To determine re-baseline clinical and MRI markers associated with SPMS diagnosis despite an early, practical, HAT. [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
At least 1 gadolinium enhancement T1 lesion on MRI
- Detremination of the impact of different definition of SPMS according to the clinician [Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).]
The definition of SPMS according to the clinician : neurological episode = start of progression as assessed by the time to develop SPMS in years.
- Dertermination of the impact of different definition of SPMS according to Lublin. [at 5 years]
The definition of SPMS according to Lublin : progressive accumulation of disability after a primary relapsing course which must be confirmed at least 6 months after, as assessed by the time to develop SPMS in years.
- Dertermination of the impact of different definition of SPMS according to Lorscheider. [at 5 years]
The definition of SPMS according to Lorscheider: with a minimum EDSS of 4 , an increase by 1 point if the EDSS was between 4 and 5.5, or an increase by 0.5 points if the EDSS was above 5.5, confirmed after 3 months., as assessed by the time to develop SPMS in years.
- Analyze of the influence of NEDA (No Evidence of Disease activity) [at baseline and at 5 years]
The disease activity will be evalued by the NEDA score
- Analyze of the influence of MEDA (Mild Evidence of Disease Activity) [at baseline and at 5 years]
The disease activity will be evalued by the MEDA score
- To find a composite score usable at baseline when prescribing early HAT in clinical practice to predict early SPMS [at 5 years]
All baseline variables will be evaluated in association with the prescriptio of an early HAT to predict early SPMS.
Eligibility Criteria
Criteria
INCLUSION CRITERIA: - Patients with RRMS (2017 Mc Donald criteria) treated with highly active treatment in the first 5 years of symptoms onset, at least 1 year, with an EDSS below 4
-
HAT start after April 12th 2007 (availability of Natalizumab)
-
Naive or failure (or intolerability) to 1 or more first line DMT (injectables, teriflunomide, DMF).
-
EDSS < or equal 4 when starting HAT EXCLUSION CRITERIA:
-
Progressive relapsing MS at baseline
-
Clinical or basic MRI data unavailable after on-site visit.
-
MS diagnostic > 5 years at baseline
-
Immunosuppressive drugs (Azathioprine, Cyclophosphamide, Mycophenolate, Methotrexate) prescribed before HAT initiation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU de Nice | Nice | France |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Nice
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 22Neuro03