Neurological

Effects of alemtuzumab on the visual system in patients with multiple sclerosis

In patients with multiple sclerosis (MS), treatment with alemtuzumab may result in partial remyelination of the lesions and have neuroprotective and promyelinating effects, according to study results published in Neurology.

While treatment options for MS aim to reduce the accumulation of lesions and cerebral atrophy, therapeutic options generally do not improve function in patients with proven disability. Alemtuzumab is an anti-CD52 monoclonal antibody approved for the treatment of relapsing MS. The data have suggested neuroprotective and restorative effects such as remyelination.

The aim of this study was to evaluate the potential neuroprotective and pro-remyelinating effects of alemtuzumab on the model of the visual pathway.

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The visual system is very susceptible to damage in patients with MS and offers a unique opportunity to assess functional structure-specific effects of various treatment options. In this study, visual evoked potential (VEP) latency was a surrogate marker for myelin integrity or recovery in the optic nerve.

The study cohort included 30 alemtuzumab-treated patients with relapsing MS aged 18 to 60 years. A reference group comprised 20 age- and gender-adjusted healthy controls.

Over a period of 24 months, the study researchers evaluated the results of clinical, multifocal VEP and magnetic resonance imaging. They performed neurological assessments including the Expanded Disability Status Scale (EDSS) score (patients only) and low contrast visual acuity (Mars letter contrast sensitivity), multifocal VEP, and baseline optical coherence tomography, 6, 12, and 24 months.

The primary endpoint was change in multifocal VEP latency. Secondary endpoints included changes in the scatter metrics of the optical radiation lesion and contrast sensitivity of the Mars letter.

Progression analysis showed an average reduction in multifocal VEP latency of 1.21 ms (95% CI, 0.21-2.21; P = 0.013) after adjustment for age, gender, duration of illness, or change in the optical exposure T2. lesion volume remained significant. In the reference group, the mean multifocal VEP latency increased by 0.72 ms throughout the study, but this was not significant.

Imaging data from chronic T2 optical radiation lesions showed a significant increase in normalized fractional anisotropy and axial diffusivity from baseline up to 24 months. The data also showed a nonsignificant reduction in normalized radial diffusivity.

In patients with MS, the mean Mars mean sensitivity of letter contrast at 24 months was improved from baseline. However, the improvement was seen in the first 6 months; no change was observed in the last 12 months of the study. The study researchers found a similar pattern of improvement in the healthy controls.

“Although our study is limited by its observational nature, relatively small size, and lack of a true control group, it nonetheless provides insights into the mechanisms of sustained clinical and MRI improvements following therapy with alemtuzumab and a framework for future remyelination studies,” the researchers concluded .

Disclosure: This research was supported by the Sanofi-Genzyme Research Grant. For a full list of specifications, see the original reference.

reference

Wang C, Barton J, Kyle K et al. Multiple sclerosis: structural and functional integrity of the visual system after alemtuzumab therapy. J Neurol Neurosurg Psychiatry. Published online June 29, 2021. doi: 10.1136 / jnnp-2021-326164

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