P33 Effect of Interferon Beta-1a SC on Demyelination in Multiple Sclerosis Patients

Saturday, June 1, 2013
Robert Zivadinov, MD, PhD, FAAN , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Michael G Dwyer, MSc , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Silva Markovic-Plese, MD, PhD , Department of Neurology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC
Cheryl Kennedy, LMSW, MPH , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Niels Bergsland, MS , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Deepa P Ramasamy, MD , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Jacqueline Durfee, BS , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
David Hojnacki, MD , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY
Brooke Hayward, SM, MBA, , EMD Serono, Inc., Rockland, MA
Fernando Dangond, MD, FAAN , EMD Serono, Inc., Rockland, MA
Bianca Weinstock-Guttman, MD , Department of Neurology, State University of New York at Buffalo, Buffalo, Buffalo, NY


Background: Although interferon beta-1a (IFN β-1a) has established efficacy in treating relapsing–remitting multiple sclerosis (RRMS), its effects have not been fully evaluated by advanced magnetic resonance imaging techniques.

Objectives: To investigate changes in remyelination/demyelination in normal appearing brain tissue (NABT) of patients with RRMS, receiving IFN β-1a versus untreated, healthy controls (HCs) who completed a 24-week study (NCT01085318), using voxel-wise magnetization transfer ratio (VW-MTR).

Methods: Increase and decrease in VW-MTR volume in NABT from baseline (BL) to 6 months were calculated in patients (n=23) treated with IFN β-1a, 44 mcg subcutaneously, three times weekly and in untreated HCs (n=15). Changes from BL to 6 months were tested using the Wilcoxon signed rank and Wilcoxon rank sum tests.

Results: A trend for an increase in VW-MTR (indicative of remyelination) over 6 months was observed for patients vs. HCs (mean [SD]: 2,473 [4,082] vs. 356 [292] mm3; p=0.061). Increase in VW-MTR for patients with RRMS vs. HCs at 3 months from BL was significant (1,467 [2,481] vs. 444 [473] mm3; p=0.028). VW-MTR decrease (indicative of demyelination) was significantly greater in patients vs. HCs at 6 months (1,346 [1,263] vs. 358 [311] mm3; p<0.001). In 2 patients with RRMS who had the highest number of gadolinium positive (Gd+) lesions at BL, markedly increased VW-MTR was observed (15,278 and 12,000 mm3).

Conclusions: Decrease in VW-MTR from BL to 6 months was greater in IFN β-1a-treated patients with RRMS than in HCs, validating this technique further as a potential tool for detecting MS disease activity over time. Findings in 2 patients with Gd+ lesions at BL and markedly increased VW-MTR changes over 6 months suggest that extensive remyelination in NABT may be ongoing in patients treated with IFN β-1a who present with increased MRI activity. These findings warrant further research in a larger study.