Neuroprotective effects underpin fingolimod benefits in MS

Jul 10 2012

By Eleanor McDermid

Fingolimod therapy reduces inflammatory activity and tissue loss in the brains of patients with multiple sclerosis (MS), shows further analysis of the FREEDOMS trial.

The FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral Therapy in MS) investigators previously reported that fingolimod reduced the relapse rate and risk for progression of disability, relative to placebo.

The latest analysis shows improved results in the fingolimod group for a range of magnetic resonance imaging (MRI) markers, including brain atrophy, represented by total brain volume. During the 24 months of the trial, placebo-treated (n=418) patients lost about 1.2% of their brain volume, but this loss was reduced by both fingolimod doses (0.5 or 1.25 mg/day; n=854), with the size of reduction versus placebo ranging from 22.7% to 44.7% at various timepoints.

The MS treatments interferon beta and natalizumab have no significant effect on brain atrophy over a similar time period, note the researchers in the Archives of Neurology.

Brain volume loss in fingolimod-treated patients was faster over the first than second years of treatment, which the team puts down to "some degree of pseudoatrophy," in which reductions in edema cause brain volume loss in addition to that caused by atrophy.

"The clinical relevance of therapeutically reduced brain volume loss is underscored by the observations that atrophy is evident during the earliest stages of MS, proceeds relentlessly throughout the course of MS at higher rates than in healthy individuals, and has a significant correlation with physical disability," say Ernst-Wilhelm Radue (University Hospital, Basel, Switzerland) and team.

"Furthermore, brain atrophy is considered to be a better MRI predictor of future disability than T2 lesion load or T1 hypointense lesion load."

Over the course of the trial, patients taking fingolimod had an average number of 2.5 new or newly enlarged T2 lesions, representing areas of recent inflammation, compared with 9.8 in those taking placebo, and the number of gadolinium-enhancing inflammatory lesions was reduced to a similar extent.

Also, the volume of T1 hypointensive lesions, representing demyelination, axonal injury, and matrix destruction, grew by an average of 30-33 mm³ in the fingolimod group, but by 173 mm³ in the placebo group.

The protective effect of fingolimod against brain atrophy was consistent irrespective of the presence of T1 and inflammatory lesions at baseline and of whether patients had previously received MS treatments.

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