This study investigated the effect on CSF biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13) following immunosuppressive therapy with mitoxantrone or rituximab in PMS.
35 people with PMS were included in the study with CSF obtained after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment and 14 age-matched healthy controls.
They found that the mean NFL level decreased by 51%, the mean CXCL13 reduction was 55%, while the levels of GFAP remained unaffected. This demonstrates that immunosuppressive therapies in relation to mitoxantrone and rituximab reduce ongoing axonal destruction in the chronic progressive phase of the disease. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and those with Gd-enhancing lesion on MRI (n=12) prior to study entry.
These results show that a proportion of people with active progressive MS may have beneficial effects from immunosuppressive therapies. This raises the question that patients should not be characterised solely based on clinical phenotype, but also on the basis of pathophysiological processes measured by MRI and biomarkers. NFL levels in CSF are a potential surrogate marker for treatment efficacy and as an endpoint in phase II trials.
Authors: Axelsson M, Malmeström C
Source: Mult Scler. 2013 May 23. [Epub ahead of print]
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