Correlations between Immunological Biomarkers and Conventional and Advanced MRI Measures Following Interferon Beta-1a Treatment for Relapsing-Remitting Multiple Sclerosis (P3.147)

OBJECTIVE: • To investigate correlations between immunological biomarkers and magnetic resonance imaging (MRI) findings following treatment with interferon (IFN) beta-1a given subcutaneously (SC) in patients with relapsing-remitting multiple sclerosis (RRMS) who had 蠅1 relapse in the 12 months prior to participation in a 6-month pilot study (NCT01085318). BACKGROUND: • Voxel-wise magnetization transfer ratio (VW-MTR) imaging is sensitive to myelin content changes in normal-appearing brain tissue (NABT) and in lesions of patients with RRMS, where decreasing and increasing volumes of VW-MTR are suggestive of demyelination and remyelination, respectively. DESIGN/METHODS: • Changes in percentage of CD4 + and CD8 + T-cells expressing pro- and anti-inflammatory cytokines were analyzed for correlations with volume changes in NABT and MS lesions (by conventional MRI and VW-MTR imaging) at baseline and 6 months after treatment with IFN beta-1a SC 44 μg, thrice weekly by Spearman’s rank correlation. RESULTS: • 15/23 patients had 蠅1 relapse in the 12 months prior to study participation. • Increases in percentage of interleukin (IL)-4-expressing CD8 + T-cells correlated with decreasing T2 lesion volume (r=-0.58; p=0.030). • Increases in percentage of IL-10-expressing CD8 + T-cells correlated with decreasing T1 lesion volume (r=-0.55, p=0.043). Increases in the percentage of IL-10-expressing CD4 + and CD8 + T-cells correlated with higher volume of increasing VW-MTR in NABT (r=0.62 and r=0.56; p=0.018 and p=0.037, respectively). • Decreases in percentage of IL-17F-expressing CD4+ T-cells correlated with lower volume of decreasing VW-MTR in NABT (r=0.69; p=0.006). CONCLUSIONS: • Elevated percentage of anti-inflammatory IL-10-expressing T-cells correlated with increasing VW-MTR volume in NABT suggestive of remyelination, and increasing IL-4 and IL-10 correlated with decreasing lesion volume. • Decreasing percentage of pro-inflammatory IL-17F cytokine-expressing CD4+ cells correlated with a smaller volume of decreasing VW-MTR signal in NABT, suggestive of decreased demyelination in patients with RRMS treated with IFN beta-1a SC. Study Supported by: EMD Serono, Inc., Rockland, MA, USA* and Pfizer Inc, New York, NY, USA. (*A subsidiary of Merck KGaA, Darmstadt, Germany) Disclosure: Dr. Markovic has received personal compensation for activities with EMD Serono. Dr. Markovic has received research support from EMD Serono, Biogen Idec., and Genzyme Corp. Dr. Tao has received personal compensation for activities with EMD Serono. Dr. Zhang has received personal compensation for activities with EMD Serono. Dr. Dwyer has received personal compensation for activities with EMD Serono and Claret. Dr. Kennedy has nothing to disclose. Dr. Bergsland has nothing to disclose. Dr. Ramasamy has nothing to disclose. Dr. Durfee has nothing to disclose. Dr. Hojnacki has received personal compensation for activities with EMD Serono. Dr. Weinstock-Guttman has received personal compensation for activities with Biogen Idec, Teva Neuroscience, EMD Serono, Pfizer, Novartis, Genzyme, Sanofi-Aventis Pharmaceuticals, Inc., Mylan, and Acorda Therapeutics. Dr. Weinstock-Guttman has received research support from Biogen Idec, Teva Neuroscience, EMD Serono, Pfizer Inc, Novartis, Acorda, ITN, Questcor, Shire, Genzyme, Sanofi-Aventis Pharmaceuticals, Inc., National Multiple Sclerosis Society, the National Institutes of Health and Aspreva-Roche. Dr. Hayward has received personal compensation for activities with EMD Serono as an employee. Dr. Dangond has received personal compensation for activities with EMD Serono, Inc. Dr. Zivadinov has received personal compensation for activities with Teva, Biogen Idec, EMD Serono, Novartis, Claret and Sanofi-Genzyme. Dr. Zivadinov has received research support from Biogen Idec, Teva Pharmaceuticals, Sanofi-Genzyme, Novartis and EMD Serono.