Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing-remitting multiple sclerosis: A retrospective analysis

Background: Changes in gray matter (GM) volume may be a useful measure of tissue loss in multiple sclerosis (MS). Objectives: To investigate the rate, patterns, and disability correlates of GM volume change in an MS treatment clinical trial. Methods: Patients (n=140) with relapsing remitting MS were randomized to intramuscular (IM) interferon (EN) beta-1a or placebo. Treatment effects on GM fraction (GMT) and white matter (WM) fraction (WMF) changes, differences in rates of GMF and WMF change in year one and two on treatment, and differences in atrophy rates by disease progression status were assessed retrospectively. Results: Significantly less GM atrophy (during year two), but not WM atrophy (at any point), was observed with IM IFN beta-1a compared with placebo. Pseudoatrophy effects were more apparent in WM than in GM; in year one, greater WM volume loss was observed with IM IFN beta-1a than with placebo, whereas GM volume loss was similar between groups. Risk of sustained disability progression was significantly associated with GM, but not WM, atrophy. Conclusions: These results suggest that GMF change is more meaningful than WMF as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials.