Real World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort

Study Overview
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Brief Summary
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Natalizumab (NTZ) use in Multiple Sclerosis (MS) in highly active patients has been largely established during the last Rationale 10 years in both clinical trials and real-world practice. Along with its efficacy, NTZ use has been limited by potential risk of progressive multifocal leukoencephalopathy (PML). Thus, several studies have tried to assess how to minimize this risk. One suggested approach is to move from the standard interval dose (SID) of 4 weeks to an extended interval dose (EID) of 5 weeks or longer. Extending the dosing interval of NTZ has been practiced by some physicians with the intention of improving the benefit/risk of the treatment by reducing the exposure-dependent risk of progressive multifocal leukoencephalopathy (PML) while maintaining efficacy. We propose to retrospectively analyze data from clinical records coming from RRMS patients treated in France at 5 different centers; Caen, Nice, Bobigny and Toulouse hospitals as well as Percy Military Hospital, to evaluate the effectiveness of natalizumab EID in subjects who have previously been treated with natalizumab SID for 12 months, in relation to continued SID treatment. In the clinical practice of these centers, patients are shifted after minimum 12 months under SID to an EID of 6 weeks regardless antibody JC serum status. Clinical, magnetic resonance imaging (MRI) and serum anti-JCV antibody status data are collected when available. The objective of this study is to assess the efficacy in term of ARR and safety.

Official Title
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Real World Effectiveness of Natalizumab Extended Interval Dosing in Relapsing-Remitting Multiple Sclerosis in a French Cohort

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Natalizumab Injection [Tysabri]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients receiving at least 11 infusions of natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing Exclusion Criteria: Patients for whom the NTZ infusion history and/or MRI and clinical history is not available. Patients with dosing gap defined as >=12 weeks between any two doses. Patients with over dose defined as <3 weeks between any two doses. Pregnancy during the follow-up period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard Interval Dosing (SID)<br>Patients continuing Natalizumab treatment with standard interval dosing defined as > 11 infusions per year | Drug: Natalizumab Injection [Tysabri]<br>* Natalizumab infusion interval according to local practice defining the patient's group<br>|
| Extended Interval Dosing (EID)<br>Patients switching to extended interval dosing defined as ≤ 10 infusions per year | Drug: Natalizumab Injection [Tysabri]<br>* Natalizumab infusion interval according to local practice defining the patient's group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Relapse Ratio | relapse rate per patient per year | baseline to 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability progression | Increase in EDSS score during the follow-up period | baseline to 12 month follow-up | 
| NEDA-3 achievement | Estimation of the proportion of patients achieving NEDA-3 criteria at the end of the follow-up period | baseline to 12 month follow-up | 
| Radiological activity | Detection of increase MRI activity defined as new or enlarged T2 lesions and/or new gadolinium enhancing lesions | baseline to 12 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natalizumab, Extended Interval Dosing