The Effects of Natalizumab and Fingolimod on Clinical, Neuropsychological and MRI Measures in Relapsing Remitting Multiple Sclerosis: A One-Year Comparative Study (P6.152)

OBJECTIVE: To compare the effects of natalizumab and fingolimod on clinical, neuropsychological (including fatigue and depression) and MRI measures in relapsing remitting (RR) multiple sclerosis (MS) after one year of treatment. BACKGROUND: Natalizumab and fingolimod reduce clinical and MRI disease activity in RRMS. DESIGN/METHODS: Forty-three RRMS patients starting natalizumab (n=19) or fingolimod (n=24) underwent 3T brain scans, clinical and neuropsychological evaluation (EDSS, Modified Fatigue Impact scale [MFIS], Montgomery-Asberg Depression Rating Scale [MADRS] and Rao’s battery) at baseline (T0), and year 1 (Y1). T2, T1 and cortical lesion volumes (LV), brain, white matter (WM), gray matter (GM) and deep GM volumes were measured. Between- and within-group analyses were performed using two- and paired-sample t-tests, and generalized linear models. RESULTS: At T0, the two groups were matched for clinical, neuropsychological and MRI variables. At Y1, disease activity and neuropsychological changes were similar between the two groups, whereas EDSS decreased significantly in fingolimod patients (p=0.006). In natalizumab patients, T2, T1 and cortical LV remained stable at Y1, while T2 (p=0.0003 vs natalizumab) and T1 (p=0.05 vs natalizumab patients) LVs significantly increased in fingolimod patients. At Y1, WMV decreased significantly in both groups. Fingolimod patients experienced significant thalamic (p=0.001) and caudate (p=0.03) atrophy. At Y1, MFIS psychosocial (MFISps) subscore improved in natalizumab (p=0.02) and worsened in fingolimod (p=0.02) (treatment-x-time interaction: p=0.001). MADRS scores were significant lower in natalizumab vs fingolimod at Y1 (p=0.04). In fingolimod, 1-year changes of caudate (β=0.028; R2=0.25, p=0.01) and thalamic (β=0.036; R2=0.22, p=0.02) volumes predicted Y1-MADRS, whereas 1-year change of caudate volume (β=0.006; R2=0.36, p=0.001) predicted Y1-MFISps subscore. CONCLUSIONS: Natalizumab and fingolimod reduce disease activity in RRMS. Natalizumab could have a more significant effect on neuropsychological aspects including emotional and behavioural functions, possibly reducing brain damage accumulation, especially in cortico-subcortical circuits.