MRI-based analysis of the natalizumab therapeutic window in multiple sclerosis

Area of Science:

• Neuroimmunology
• Radiology
• Clinical Neurology

Background:

• Natalalizumab is a standard treatment for relapsing-remitting multiple sclerosis (RRMS).
• The recommended dosing schedule is 300 mg every 4 weeks.
• Understanding the impact of dosing delays on disease activity is critical for optimizing patient outcomes.

Purpose of the Study:

• To evaluate the relationship between the time since the last natalizumab infusion and radiological activity in RRMS patients.
• To determine the risk of magnetic resonance imaging (MRI) activity associated with delayed natalizumab dosing.

Main Methods:

• Retrospective analysis of 386 MRI scans from 166 natalizumab-treated RRMS patients.
• Scans were assessed for radiological activity (contrast-enhancing lesions) at various intervals after the last natalizumab infusion.
• Comparison of activity in patients with delayed infusions versus those adhering to the 4-week schedule.

Main Results:

• Of 113 scans performed more than 4 weeks after the last infusion, 26 showed radiological activity.
• The risk of radiological activity increased by 1.34-fold for each week of delay beyond the recommended 4-week interval (p<0.0001).
• Significantly higher MRI activity was observed in patients with delayed dosing compared to schedule-adherent patients.

Conclusions:

• Delayed natalizumab infusions beyond the recommended 4-week interval are associated with a significant increase in radiological activity in RRMS.
• An increased risk of MRI activity at or after 7 weeks from the last infusion should be considered when discontinuing natalizumab therapy.
• Maintaining the recommended dosing schedule is important for controlling disease activity in natalizumab-treated RRMS patients.