Improvement in Cognitive Function as Measured by NeuroTrax in Patients with Relapsing Multiple Sclerosis Treated with Natalizumab: A 2-Year Retrospective Analysis

Abstract

Background Cognitive impairment affects many patients with multiple sclerosis (MS). NeuroTrax, a computerized cognitive screen that can be administered during routine clinical care, provides a consistent, validated, objective cognitive profile measure with a global cognitive score (GCS) and seven individual domain scores. Natalizumab is an efficacious therapy for relapsing MS, demonstrating reductions in disability worsening and MS disease activity measured by magnetic resonance imaging. Objective The aim of this study was to assess cognitive function as measured by NeuroTrax in MS patients treated with natalizumab for ≥ 2 years. Methods This retrospective observational study included adult MS patients in the United States who received 300 mg intravenous natalizumab every 4 weeks for ≥ 2 years. NeuroTrax data were evaluated at baseline and yearly thereafter. Changes in GCS and the seven individual cognitive domain scores from baseline to after 24 infusions of natalizumab were analyzed. Results In the study population at baseline (N = 52), 22 patients (42.3%) had disease duration of 0-5 years; 12 patients (23.1%) were treatment naive. GCS score improved significantly from baseline [mean 95.5, standard deviation (SD) 12.9] to year 2 (mean 98.9, SD 13.2; change from baseline 3.4; p = 0.003). After 2 years on natalizumab, 17 patients (32.7%) demonstrated clinically significant improvement (increase from baseline > 1 SD) in GCS. Results were similar regardless of whether patients had previously received MS therapy. Conclusions Patients treated with natalizumab demonstrated significant improvement in cognitive function, measured by NeuroTrax GCS, over 2 years of treatment. Key PointsNatalizumab significantly improved NeuroTrax global cognitive score over 2 years of treatment, regardless of whether patients were treatment-naive or were previously treated with other disease-modifying therapies.Numerical improvements were observed for all seven individual cognitive domains from baseline to 2 years.These results indicate that some aspects of cognitive impairment can be reduced in patients with multiple sclerosis treated with natalizumab.

Cognitive function in multiple sclerosis: A long-term look on the bright side

“…Testing time was approximately 45 min. The computerized cognitive battery has shown good test-retest reliability and construct validity relative to paper-based tests, including the frequently used Neuropsychological Screening Battery for MS, NSBMS, [3], as well as sensitivity to effects of DMD in MS [7].…”

“…Cognitive impairment was significant only at disease duration greater than five years suggesting the existence of an early therapeutic window [5]. However, the effects of disease modifying drugs (DMD) on cognitive impairments in MS have not been thoroughly studied [6], though several DMD have demonstrated a beneficial effect on cognitive performance [7] and spared brain atrophy [8–10], thus showing the potential to decrease cognitive decline.…”

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS

“…Natalizumab administered intravenously every 4 weeks (Q4W 1 ) is an efficacious treatment for relapsing forms of multiple sclerosis (MS), as demonstrated by randomized clinical trials and real-world evidence (Butzkueven et al, 2020;Capra et al, 2020;Gudesblatt et al, 2018;Horakova et al, 2020;Perumal et al, 2019;Polman et al, 2006;Wiendl et al, 2020). However, Q4W natalizumab dosing is associated with a risk of progressive multifocal leukoencephalopathy (PML) in anti-JC virus (JCV) antibody-positive patients (Bloomgren et al, 2012;Ho et al, 2017).…”

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

“…Several studies have suggested that DMTs may improve cognitive function or slow cognitive decline, [136][137][138][139][140][141] although it is unclear if this is due to a reduction in MRI disease seen with these agents. The overall evidence does not link any specific agent consistently with improvement in cognitive function nor does it support switching agents to benefit cognition.…”