Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis.
BACKGROUND
This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers.


METHODS
In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays.


RESULTS
There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL).


CONCLUSIONS
Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta.
Petzold
A
A
Institute of Neurology, Department of Neuroimmunology, Queen Square, London WC1N 3BG, UK. a.petzold@ion.ucl.ac.uk
Brassat
D
D
Mas
P
P
Rejdak
K
K
Keir
G
G
Giovannoni
G
G
Thompson
E J
EJ
Clanet
M
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009414:Nerve Growth Factors / Q000097:blood; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D009414:Nerve Growth Factors; D009566:Nitrates; D009573:Nitrites; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016899:Interferon-beta