Multiple Sclerosis: Chi3L1 and Treatment Efficacy

Study Overview
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Brief Summary
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Chitinase 3-like 1 (Chi3L1) is a Human protein synthetized by inflammatory cells. Its serum level increases in case of autoimmune diseases, and especially during multiple sclerosis (MS). There is a need for biological markers predictive of treatment efficacy. MS outcomes one year from treatment initiation are predictive of long-term treatment efficacy. The hypothesis is that serum Chi3L1 level before treatment initiation could predict one year MS outcomes. Primary objective: to show an association between the serum Chi3L1 level at diagnostic assessment and the clinical and radiological efficacy one year from initiation of the first disease modifying treatment (interferon beta, dimethyl fumarate or teriflunomide) in relapsing-onset multiple sclerosis (MS). Secondary objectives: to determine the threshold value of the serum Chi3L1 level predicting the efficacy of treatment, and the added value of other potential biomarkers in cerebrospinal fluid collected at diagnostic assessment: Chi3L1, light chains of neurofilaments and interleukin 6.

Official Title
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Chi3L1: A Marker of Efficacy of Platform Treatments in Relapsing-onset Multiple Sclerosis: A Prognostic Study on Existing Clinical Data and Biological Samples

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Interferon-Beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsing-onset multiple sclerosis according to the 2017 McDonald criteria Blood and cerebrospinal fluid samples collected at diagnostic assessment from 2012 January 1st and kept in the Centre de Ressources Biologiques Lorrain First platform disease modifying drugs : interferon-Beta, dimethyl fumarate or teriflunomide, introduced during the first 3 months after the diagnostic assessment Disease modifying drugs maintained at least 3 months Follow-up during at least 15 months after the first disease modifying drug initiation At least one brain magnetic resonance imaging with gadolinium injection between months 3 and 15 after disease modifying drug initiation Exclusion Criteria: Objection to the use of personal data for research purpose

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Interferon-Beta<br>Patients with first treatment : interferon beta (1a subcutaneous 22 or 44 µg thrice a week OR 1a intramuscular 30 µg once a week OR 1b subcutaneous 250 µg every other day OR 1a PEGylated subcutaneous 125 µg every two weeks) | Drug: Interferon-Beta<br>* Theses drugs have been administered as part of routine care. Biological samples that will be analyzed (blood and cerebrospinal fluid) have been taken as part of routine care.<br>* Other names: Teriflunomide;|
| Dimethyl fumarate<br>Patients with first treatment : dimethyl fumarate (oral, 240 mg twice a day) | |
| Teriflunomide<br>Patients with first treatment : teriflunomide (oral, 14 mg once a day) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Statistical association between the baseline chitinase 3-like 1 serum level and being responder at year one | Significant associations in each group of treatment Being responder means the presence of the four following : No treatment withdrawal between months 3 and 15 after treatment initiation for reason of inefficacy No relapse between months 3 and 15 No increase of at least one point on the expanded disability status scale between months 3 and 15 No gad-enhancing lesion on any magnetic resonance imaging scan between months 3 and 15 If any of these criteria is lacking, then the patient is considered as non-responder. | Baseline to month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Threshold chitinase 3-like 1 serum level at baseline to distinguish responders from non-responders | Threshold measure that discriminates responders and non-responders at month 15 in each group | Baseline to month 15 | 
| Statistical association between the baseline chitinase 3-like 1 cerebrospinal fluid level and being responder at year one | Significant associations in each group of treatment Being responder means the presence of the four following : No treatment withdrawal between months 3 and 15 after treatment initiation for reason of inefficacy No relapse between months 3 and 15 No increase of at least one point on the expanded disability status scale between months 3 and 15 No gad-enhancing lesion on any magnetic resonance imaging scan between months 3 and 15 If any of these criteria is lacking, then the patient is considered as non-responder. | Baseline to month 15 | 
| Statistical association between the baseline neurofilaments light chains cerebrospinal fluid level and being responder at year one | Significant associations in each group of treatment Being responder means the presence of the four following : No treatment withdrawal between months 3 and 15 after treatment initiation for reason of inefficacy No relapse between months 3 and 15 No increase of at least one point on the expanded disability status scale between months 3 and 15 No gad-enhancing lesion on any magnetic resonance imaging scan between months 3 and 15 If any of these criteria is lacking, then the patient is considered as non-responder. | Baseline to month 15 | 
| Statistical association between the baseline interleukin 6 cerebrospinal fluid level and being responder at year one | Significant associations in each group of treatment Being responder means the presence of the four following : No treatment withdrawal between months 3 and 15 after treatment initiation for reason of inefficacy No relapse between months 3 and 15 No increase of at least one point on the expanded disability status scale between months 3 and 15 No gad-enhancing lesion on any magnetic resonance imaging scan between months 3 and 15 If any of these criteria is lacking, then the patient is considered as non-responder. | Baseline to month 15 |