MRI outcomes show weak association with disability in primary progressive multiple sclerosis patients

This Phase 3 trial secondary analysis included 943 patients with primary progressive multiple sclerosis treated with glatiramer acetate. The baseline population had a mean age of 58.0 years, mean EDSS of 5.0, and mean disease duration of 10.5 years. Follow-up duration was 2 years. The study examined longitudinal associations between MRI outcomes and disability changes.

The intervention or exposure focused on MRI outcomes including grey matter volume, white matter volume, brain fraction, and total burden of disease. No comparator was reported. The primary outcome assessed the longitudinal association between change in MRI outcomes and change in disability. Secondary outcomes included grey matter volume, white matter volume, brain fraction, total burden of disease, EDSS, Timed 25 Foot Walk, Nine-Hole Peg Test, and Paced Auditory Serial Addition Test.

Main results indicated only weak and inconsistent associations found between change in MRI and physical and cognitive outcome measures. Specifically, change in MRI measures in year 1 did not predict change in physical nor cognitive disability in year 2. Effect size, absolute numbers, and p-value or confidence interval were not reported. The direction of association was weak and inconsistent.

Safety data regarding adverse events, serious adverse events, discontinuations, and tolerability were not reported. Limitations included weak and inconsistent associations between MRI measures and clinical disability outcomes. Practice relevance suggests findings question the suitability of brain volume loss and lesion burden accumulation as functionally relevant trial endpoints in PPMS. Causation was not established, and findings are based on weak and inconsistent associations.