CMSC 2012: Fingolimod Slows Brain Volume Loss and May Be Neuroprotective

SAN DIEGO — The once-daily oral multiple sclerosis (MS) drug, fingolimod, slows brain volume loss in patients with MS, regardless of inflammatory activity, according to research presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Fingolimod is the first in a new class of sphingosine 1-phosphate receptor modulators that works by sequestering lymphocytes in lymph nodes, preventing them from mounting an autoimmune attack. Fingolimod is approved for the treatment of patients with relapsing-remitting MS (RRMS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.

Typically, change in normalized brain volume, as assessed using magnetic resonance imaging (MRI), can be a sensitive indicator of MS disease progression, although it can be affected to a certain degree by fluid shifts related to changes in inflammatory status. Here, the goal was to evaluate, using MRI inflammatory marker status, whether fingolimod slows brain atrophy after 1 year of treatment.

Frederik Barkhof, MD, of VU University Medical Center in Amsterdam, The Netherlands, and colleagues conducted a study involving a representative subset of patients with RRMS who had participated in the phase 3 TRANSFORMS study who were treated with fingolimod 0.5 mg, 1.25 mg, or weekly intramuscularly administered interferon (IFNbeta-1a) 30 mcg for one year. Mean percentage brain volume change was assessed using MRI scans at baseline and at 1 year based on the presence or absence of gadolinium-enhancing (Gd+) lesions and/or new/newly enlarged T2 lesions.

In the TRANSFORMS study, fingolimod 0.5 mg reduced brain volume loss by 31% compared with IFNbeta-1a. Similar results were achieved in this subset of patients. Compared with IFNbeta-1a treatment, MRI assessed brain volume at 1 year was statistically significantly reduced by approximately 30% to 40% in fingolimod-treated patients without Gd+ lesions at baseline, those with and without MRI disease activity at 1 year, and those with either baseline or month 12 Gd+ lesions or new/newly enlarged T2 lesions at 1 year. Reductions were not statistically significant for patients with Gd+ lesions at baseline treated with either fingolimod dose or for patients without baseline Gd+ lesions or new MRI disease activity at month 12 treated with fingolimod 0.5 mg.

“Compared with IFNbeta-1a IM, fingolimod reduced the amount of brain volume loss over 1 year in patients without inflammatory lesion activity and, to a lesser degree, in patients with inflammatory lesion activity. These results suggest that fingolimod may have a neuroprotective effect, either directly, or owing to reduced inflammation,” the authors concluded.

This research was supported by Novartis Pharmaceuticals Corp.