Effects of Natalizumab on Cognition and Neurodegeneration in Relapsing-Remitting Multiple Sclerosis (P4.172)

OBJECTIVE: To investigate how early treatment with natalizumab affects markers of neurodegeneration and cognitive function in patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: Brain atrophy can occur early in the disease course of RRMS and lead to clinical disability and cognitive dysfunction. These changes may be delayed or reduced by natalizumab. DESIGN/METHODS: We conducted an ongoing, prospective, 96 week, single center, parallel group study of 20 patients with RRMS treated open-label with natalizumab. Analysis compared patients that started treatment less than two years after diagnosis with those starting treatment more than two years after diagnosis. Measures of neurodegeneration and cognitive function between the two groups were compared, with observations at baseline and follow-up after 24, 48, 72, and 96 weeks. Parameters measured included cognitive function indicated by Symbol-Digit Modalities Test (SDMT) z-scores, non-conventional MRI metrics estimated by FSL, and retinal nerve fiber layer thickness and macular volume as measured by optical coherence tomography (OCT). RESULTS: An interim analysis of the 8 patients that have completed 48 weeks of treatment revealed that those in the early treatment group had an increase in SDMT z-scores of 0.64 standard deviations that trended towards significance (p = 0.085). Those in the late treatment group did not see a change. For the cohort, cognitive decline was correlated with thalamic atrophy (r = 0.92, p < 0.05) but not whole brain atrophy. There was a trend towards a decrease in white matter fraction (-0.68 ± 0.80 %, p = 0.064) while gray matter fraction increased (0.63 ± 0.77 %, p = 0.075). There were no noticeable longitudinal changes in OCT measurements. CONCLUSIONS: These findings suggest that treatment of RRMS with natalizumab early in the disease course may protect cognitive function. Further investigation into brain atrophy from week 48 to week 96 is warranted to evaluate neurodegeneration in the absence of pseudoatrophy. Study Supported by: Biogen; Ruth L. Kirchstein National Research Service Award Short-Term Institutional Research Training Grant 2T35DK062719-26 Disclosure: Dr. Talmage has nothing to disclose. Mr. Coppes has received research support from Teva Neuroscience. Dr. Finch has nothing to disclose. Dr. Sprayberry has nothing to disclose. Dr. Javed has received personal compensation for activities with Teva Neuroscience, Bayer Pharmaceuticals Corp., Novartis, Questcor Diagnostics, and Biogen Idec as a consultant and speaker. Dr. Bernard has received personal compensation for activities with Biogen Idec and Bayer Pharmaceuticals Corporation. Dr. Bernard has received research support from Biogen Idec.