Chronic lesion activity and disability progression in secondary progressive multiple sclerosis

Area of Science:

• Neuroscience
• Radiology
• Clinical Trials

Background:

• Slowly expanding lesions (SELs) are chronic white matter lesions in multiple sclerosis (MS) that predict disability accumulation.
• The interplay between SELs, acute lesion activity (ALA), chronic lesion activity (CLA), and disability progression in MS remains incompletely understood.

Purpose of the Study:

• To investigate the relationships between SELs, ALA, CLA, and disability progression in patients with secondary progressive multiple sclerosis (SPMS).
• To evaluate the effect of natalizumab on SELs, ALA, and CLA in the ASCEND phase III clinical trial.

Main Methods:

• Analysis of imaging data from 600 SPMS patients in the ASCEND trial (natalizumab vs. placebo) from baseline to 108 weeks.
• Assessment of SEL prevalence, disability progression, ALA (gadolinium-enhancing and new T2 lesions), and CLA (T1-hypointense lesion volume increase).

Main Results:

• CLA was higher in SPMS patients with disability progression, irrespective of SEL presence.
• In the absence of ALA, SEL prevalence was lower, but CLA in non-SELs still correlated with disability progression.
• Natalizumab significantly reduced SEL prevalence and CLA in both SELs and non-SELs compared to placebo.

Conclusions:

• Chronic lesion activity (CLA) in SPMS is associated with disability progression, even without acute lesion activity.
• Therapeutic strategies should address all mechanisms of CLA, including smoldering inflammation and neurodegeneration.
• Natalizumab demonstrates efficacy in reducing lesion activity and may impact disability progression in SPMS.