Effect of disease-modifying therapies on brain volume in relapsing-remitting multiple sclerosis: results of a five-year brain MRI study

Objective: To compare the long-term effect of disease-modifying therapies (DMT) on brain volume loss in relapsing-remitting MS (RRMS) patients.

Methods: We conducted a study to examine the effect of daily glatiramer acetate (GA), weekly low dose interferon beta (LD-IFNB), and high-dose high-frequency interferon beta disease (HD-IFNB) on brain volume loss over 5 years in RRMS patients. All patients were previously treatment naïve, had disease duration ≤5 years at the time of initiating DMT, and subsequently received the same DMT for 5 years continuously. The percentage change in brain volume (PCBV) was measured using fully automated software. MRI analysis was performed blinded to treatment allocation.

Results: The adjusted PCBV from baseline to year 5 was -2.27% in GA, -2.62% in LD-IFNB, and -3.21% in the HD-IFNB groups (-2.27 vs -2.62, p=0.0036; -2.27 vs -3.21, p<0.0001; -2.62 vs -3.21, p<0.0001). These data remained unchanged from year 1 to year 5, after adjusting for pseudoatrophy in the first year. A group of RRMS patients that remained untreated for a period ranging from 8 to 24 months, served as controls. All treatment groups were significantly better than the rate of projected brain volume loss in the untreated group over 5 years (p<0.0001).

Conclusions: Global brain volume loss is a dynamic process even in relatively early RRMS patients that occurs despite intervention with therapy. However, all DMT significantly reduced the loss of brain volume compared to no treatment. The GA-treated group experienced the least reduction in brain volume over 5 years, compared to the LD-IFNB and HD-IFNB treated groups. These differences could be partly related to the immunologic consequences of GA therapy in RRMS.