SAN DIEGO—Fingolimod slows brain atrophy in patients with multiple sclerosis (MS) and is the only approved drug that does so within the first six months of treatment, reported Jeffrey Cohen, MD, at the 65th Annual Meeting of the American Academy of Neurology.
The findings come from a combined analysis of the drug’s three clinical trials—FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which compared 0.5 mg and 1.25 mg daily against placebo for two years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which compared those doses against weekly intramuscular interferon beta-1a for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation using normalization of atrophy) at baseline and at six, 12, and 24 months. More than 3,000 patients ages 18 to 55 with clinically active relapsing-remitting MS participated.
“There was a consistent” 31% to 36% reduction in the rate of brain volume loss with both doses of fingolimod “compared to placebo and interferon beta-1a,” said Dr. Cohen. “There was no clear-cut dose effect between the two” doses. Dr. Cohen is Director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research, Cleveland Clinic.
In the two trials with placebo arms, patients who had received fingolimod had volume losses of about 0.85%, compared with 1.31% in patients who had received placebo. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The “benefit was seen as early as six months, in both FREEDOMS and FREEDOMS II,” said Dr. Cohen. “In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss—in other words, no pseudoatrophy.”
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab and glatiramer acetate, he noted.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who received it, regardless of baseline characteristics, according to Dr. Cohen.
Weak correlations were observed between accumulations of T2 lesions and disability during the study, perhaps because “brain volume and measures of disability don’t change much over two years,” Dr. Cohen said.
—M. Alexander Otto
IMNG Medical News