Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis
2014 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 1, 43-50 p.Article in journal (Refereed) Published
Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
Place, publisher, year, edition, pages
Sage Publications, 2014. Vol. 20, no 1, 43-50 p.
Multiple sclerosis, immunosuppressive therapy, mitoxantrone, rituximab, biomarkers, cerebrospinal fluid, neurofilament light protein, glial fibrillary acidic protein, CXCL13, axonal damage
IdentifiersURN: urn:nbn:se:umu:diva-84771DOI: 10.1177/1352458513490544ISI: 000328607800009OAI: oai:DiVA.org:umu-84771DiVA: diva2:695146