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Among patients with multiple sclerosis (MS), treatment with alemtuzumab may result in partial lesion remyelination and may have neuroprotective and promyelinating effects, according to study results published in Neurology.
While treatment options for MS are aimed at reducing the accumulation of lesions and brain atrophy, therapeutic options generally do not improve function in patients with established disability. Alemtuzumab is an anti-CD52 monoclonal antibody approved for the treatment of relapsing MS. Data has suggested a neuroprotective mode of action and restorative effects, such as remyelination.
The objective of this study was to assess the potential neuroprotective and pro-remyelinating effects of alemtuzumab using the visual pathway as a model.
The visual system is highly susceptible to damage in patients with MS and presents a unique opportunity to assess function-structure specific effects of various treatment options. In this study, latency of the visual evoked potential (VEP) was a surrogate marker of 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 included 20 age- and sex-matched healthy controls.
Over 24 months, study researchers evaluated clinical, multifocal VEP, and magnetic resonance imaging outcomes. They conducted neurological assessments, including Expanded Disability Status Scale (EDSS) score (patients only) and low contrast visual acuity (Mars letter contrast sensitivity), multifocal VEP, and optical coherence tomography at baseline, 6, 12 and 24 months.
The primary outcome was change in multifocal VEP latency. Secondary endpoints included change in optic radiation lesion diffusion metrics and Mars letter contrast sensitivity.
Progression analysis showed a mean shortening of multifocal VEP latency of 1.21 ms (95% CI, 0.21-2.21; P =.013) throughout the study, which remained significant after adjusting for age, gender, disease duration, or change in optic radiation T2 lesion volume. In the reference group, mean multifocal VEP latency increased throughout the study by 0.72 ms, but this was not significant.
Imaging data of chronic optic radiation T2 lesions indicated significant elevation of normalized fractional anisotropy and axial diffusivity from baseline to 24 months. Data also indicated a nonsignificant reduction in normalized radial diffusivity.
Among patients with MS, the mean Mars average letter contrast sensitivity was improved at 24 months compared with baseline. However, the improvement was seen in the first 6 months; no change was observed in the latter 12 months of the study. Study researchers noted a similar pattern of improvement in the healthy controls.
“Although limited by its observational nature, relatively small size and lack of a true control group, our study nevertheless provides insights into the mechanisms of sustained clinical and MRI improvements following therapy with alemtuzumab and a framework for future remyelination trials,” concluded the researchers.
Disclosure: This research was supported by Sanofi-Genzyme Research Grant. Please see the original reference for a full list of disclosures.
Reference
Wang C, Barton J, Kyle K, et al. Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy. J Neurol Neurosurg Psychiatry. Published online June 29, 2021. doi:10.1136/jnnp-2021-326164
