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Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis
University of Gothenburg, Gothenburg, Sweden .
University of Gothenburg, Gothenburg, Sweden .
Örebro universitet, Institutionen för läkarutbildning. Region Örebro län.
University of Gothenburg, Mölndal, Sweden; Institute of Neurology, The University College London (UCL), London, UK.
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2014 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 1, s. 43-50Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
London, United Kingdom: Sage Publications, 2014. Vol. 20, nr 1, s. 43-50
Nyckelord [en]
Multiple sclerosis, immunosuppressive therapy, mitoxantrone, rituximab, biomarkers, cerebrospinal fluid, neurofilament light protein, glial fibrillary acidic protein, CXCL13, axonal damage
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URN: urn:nbn:se:oru:diva-33142DOI: 10.1177/1352458513490544ISI: 000328607800009PubMedID: 23702432Scopus ID: 2-s2.0-84890808806OAI: oai:DiVA.org:oru-33142DiVA, id: diva2:694524
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Funding Agencies:

Swedish Federal Government (LUA/ALF)

Swedish Society of the Neurologically Disabled

Research Foundation of the Multiple Sclerosis Society of Gothenburg

Edit Jacobson Foundation

BiogenIdec

Tillgänglig från: 2014-02-06 Skapad: 2014-01-17 Senast uppdaterad: 2018-06-04Bibliografiskt granskad

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Gunnarsson, Martin

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