Alemtuzumab preserves neuroaxonal structure in MS

Multiple sclerosis

By Michael Woodhead

4 Mar 2020

Dr Ai-Lan Nguyen

Alemtuzumab, the anti-CD52 monoclonal antibody used to treat relapsing–remitting MS (RRMS), appears to protect neuroaxonal structure compared to other first-line injectable treatments, a multinational study has found.

The findings comes from a five year study that used optical coherence tomography (OCT) measures of neuroaxonal structure to compare the effects of alemtuzumab treatment in 24 RRMS patients compared to either interferon-b or glatiramer acetate (N = 21) in other RRMS patients.

A multinational team including Dr. Ai-Lan Nguyen of the Royal Melbourne Hospital found that over a median of 60 months (range 42–60 months), the alemtuzumab cohort demonstrated a change in the mean retinal nerve fibre layer (RNFL) thickness (thinning from baseline) of 20.88 mm and mean ganglion cell inner plexiform (GCIP) layer volume of +0.013 mm3.

Over the same time period, the first-line therapy–treated cohort showed greater degrees of RNFL thinning (mean change in RNFL thickness was 23.65 mm. There was also more prominent GCIP volume loss relative to baseline in the first-line therapy group (20.052 mm3).

The study authors noted that the effect of alemtuzumab on thinning was less in patients with a history of optic neuritis compared to those without optic neuritis

“This may suggest that treatment has less of an effect on RNFL neurodegeneration after an episode of ON compared with eyes without a history of ON, supporting earlier initiation of higher efficacy treatment,” they wrote.

While acknowledging that the retrospective study was exploratory, they said the findings support the hypothesis that alemtuzumab facilitates neurostability in MS.

It was notable that alemtuzumab-treated MS patients showed no significant loss of RNFL thickness or GCIP volume in contrast to those receiving first-line therapies who showed significant RNFL thinning and GCIP volume loss “indicating accrued neuroaxonal damage in the afferent visual pathway,” they said

“These observations were noteworthy because alemtuzumab-treated patients had worse measures of MS disease activity and disability at study entry and would have been expected to demonstrate more severe neuroaxonal injury, compared with their MS counterparts receiving first-line therapies over 5 years,” they wrote.

And since earlier and greater loss of neuroaxonal substrate translates to poorer neurological outcomes, this suggested that early treatment with a highly effective immune therapy may be necessary to halt progressive neuronal loss and axonal damage, they added.

“These findings, along with previous demonstration of improved brain atrophy rates, suggest that alemtuzumab may offer long-term preservation of neuroaxonal structure in patients with RRMS,” they concluded.

The findings are published in the Journal of Neuro-Ophthalmology.

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