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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Natalizumab Injection [Tysabri]

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• France
  • Bobigny, France, 93000
    • Department of Neurology, CHU Bobigny-Avicenne
  • Caen, France, 14000
    • Department of Neurology, CHU de Caen
  • Clamart, France, 92140
    • Department of Neurology, Percy Military Hospital
  • Nice, France, 06000
    • Department of Neurology, CHU Nice
  • Toulouse, France, 31300
    • Department of Neurology, CHU Toulouse Purpan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients receiving Natalizumab as disease-modifying monotherapy for RRMS

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome	Description of PML cases and variations in anti-JCV antibody status when available	baseline to 12 month follow-up

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Collaborators: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 30, 2021

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Natalizumab; Extended Interval Dosing
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: FRA-TYS-19-11504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No