Longitudinal assessment of neurocognitive function in people with relapsing multiple sclerosis initiating alemtuzumab in routine clinical practice: LEM-COG study results

•Neurocognitive function was assessed in RMS population treated with alemtuzumab.•MS-COG composite score improved significantly from baseline to month 12 follow-up.•Improvement in MS-COG seems to be driven by improvement in processing speed.•Over 12 months, about 92% of population showed stable or improved cognitive status. Alemtuzumab is effective in reducing relapse rate and disability, but limited data exist on its effect on cognitive function in relapsing multiple sclerosis (RMS). The present study assessed neurocognitive function and safety associated with alemtuzumab treatment in RMS. This longitudinal, single-arm, prospective study included people with RMS (aged 25–55 years) who were treated with alemtuzumab in clinical practice in the United States of America and Canada. The first participant was enrolled in December 2016. The primary endpoint was the change from baseline to post-baseline (month [M] 12/24) in MS-COGnitive (MS-COG) composite score. Secondary endpoints included Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), Selective Reminding Test (SRT), Controlled Oral Word Association Test (COWAT), and Automated Neuropsychological Assessment Metrics (ANAM) scores. Depression and fatigue were assessed using Hamilton Rating Scale-Depression (HAM-D) and Fatigue Severity Scale (FSS)/Modified Fatigue Impact Scale (MFIS), respectively. Magnetic resonance imaging (MRI) parameters were assessed when available. Safety was assessed throughout the study. Descriptive statistics were used for the pre-specified statistical analyses. Since the study was terminated early (November 2019) because of operational and resource difficulties, post hoc analyses for statistical inference were performed among participants who had a baseline value and at least one complete post-baseline assessment for cognitive parameters, fatigue, or depression. Of the 112 participants enrolled, 39 were considered as the primary analysis population at M12. At M12, a mean change of 0.25 (95% confidence interval [CI]: 0.04, 0.45; p = 0.0049; effect size [ES]: 0.39) was observed in the MS-COG composite score. Improvements were observed in processing speed (based on PASAT and SDMT; p < 0.0001; ES: 0.62), as well as in individual PASAT, SDMT and COWAT scores. An improvement was also noted in HAM-D (p = 0.0054; ES: –0.44), but not in fatigue scores. Among MRI parameters, decreases in burden of disease volume (BDV