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

Completed

• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Interventions: Drug: Natalizumab Injection [Tysabri]

• Registration Number: NCT04580381
• Lead Sponsor: University Hospital, Caen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-09
• Study Start: 2020-09-01
• Study First Submitted: 2020-10-02
• Study First Submitted QC: 2020-10-02
• Study First Posted: 2020-10-08
• Primary Completion: 2021-10-01
• Study Completion: 2021-10-30
• Last Update Submitted: 2022-03-08
• Last Update Posted: 2022-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Standard Interval Dosing (SID)	Natalizumab Injection [Tysabri]	Patients continuing Natalizumab treatment with standard interval dosing defined as \> 11 infusions per year
Extended Interval Dosing (EID)	Natalizumab Injection [Tysabri]	Patients switching to extended interval dosing defined as ≤ 10 infusions per year

Primary Outcome Measures

Name	Time	Method
Annualized Relapse Ratio	baseline to 12 month follow-up	relapse rate per patient per year

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Department of Neurology, CHU de Caen; 🇫🇷 Caen, France

Department of Neurology, CHU Bobigny-Avicenne; 🇫🇷 Bobigny, France

Department of Neurology, Percy Military Hospital; 🇫🇷 Clamart, France

Department of Neurology, CHU Toulouse Purpan; 🇫🇷 Toulouse, France

Department of Neurology, CHU Nice; 🇫🇷 Nice, France