Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation

Area of Science:

• Neurology
• Immunology
• Radiology

Background:

• Natalizumab therapy for multiple sclerosis (MS) carries a risk of progressive multifocal encephalopathy (PML) after 24 months.
• Balancing PML risk with disease control necessitates understanding optimal natalizumab discontinuation strategies.

Purpose of the Study:

• To compare immediate versus tapered natalizumab cessation interventions.
• To assess the impact on relapse rates and MRI-defined disease activity over 12 months.

Main Methods:

• A 12-month, single-blinded, randomized controlled trial involving 50 MS patients on natalizumab for ≥24 months.
• Participants were randomized to immediate discontinuation (IDG) or a tapered regimen (TG) with two additional infusions.
• Serial MRI scans were performed at baseline, 6, and 12 months post-last infusion.

Main Results:

• The immediate discontinuation group (IDG) experienced significantly more relapses (28 vs 8) and earlier relapses (within 3 months) compared to the tapered group (TG).
• IDG showed increased new T2 lesions (6-12 months), higher mean T2-LV change (0-12 months), and more new T1-hypointense lesions (0-12 months and baseline-6 months) versus TG.
• These findings indicate greater disease activity in the immediate discontinuation group.

Conclusions:

• Natalizumab discontinuation is associated with new disease activity in MS patients.
• A tapered cessation protocol demonstrated benefits, leading to fewer relapses and reduced MRI lesion accumulation compared to immediate discontinuation.