Supplementary Table 4: Summary of discussed studies on biomarkers for treatment response in the period 2012–2015
Blood biomarker
Clinical purpose
Cohorts of the
Novel information
Cohort
initial studies
obtained in 2012–
confirmation
(diagnosis and
2015
studies (number of
number of patients)
Anti-IFNβ Nab
Response to IFNβ1
Numerous studies,
Remarks
patients)
Numerous studies,
RRMS n = 1642
2773
reviewed by Polman
lack novelty to
RRMS n =
et al.1
previous published
RRMS n = 1184
work
IFNβ-Abs are early
predictors Nab
MxA miRNA
correlated to
disability progression
in IFNβ treatment
Antibody dissociation
rates predict
persistence of antiIFNβ-1b Nab
Anti-natalizumab
Response to
(Nab)
natalizumab5
IL-17F
Response to IFNβ8
RRMS n = 6255
RRMS n = 268
Confirmation of initial
RRMS n = 736
clinical purpose6,7
RRMS n = 1,3797
Initial findings
RRMS n = 2399
confirmed only for
very high levels9
miRNA
Response to IFNβ
Initial clinical
RRMS n = 610
purpose10,11
RRMS n = 6011
Anti-JCV antibodies
Predicting risk of
PML n = 54 and non-
Confirmation of initial
PML n = 71 PML
PML12
PML n = 5,89612
clinical purpose13
and non-PML
n = 2,52213
L-selectin-expressing
Predicting risk of
PML n = 16
Initial clinical
CD4+ T cells
PML
Non-PML n = 28914
purpose
Lipid-specific IgM
Predicting risk of
PML n = 24
Initial clinical
oligoclonal bands
PML
Non-PML n =
34315
purpose
Abbreviations: IF-17F; interleukin 17F, IFNβ; interferon-beta, IgM, immunoglobulin M, JCV; John Cunnigham virus, miRNA; microRNA, Nab;
neutralizing antibody, MxA; myxovirus-induced protein A, non-PML; patients without progressive multifocal leukoencephalopathy, PML;
progressive multifocal leukoencephalopathy RRMS; relapsing remitting multiple sclerosis.
1.
Polman, C. H. et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. Lancet.
Neurol. 9, 740–50 (2010).
2.
Hegen, H. et al. Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing
antibody development. Mult. Scler. J. 20, 577–587 (2013).
3.
Gibbs, E., Karim, M. E. & Oger, J. Antibody dissociation rates are predictive of neutralizing antibody (NAb) course: A comparison of interferon beta-1btreated patients with transient versus sustained NAbs. Clin. Immunol. 157, 91–101 (2014).
4.
Serana, F. et al. MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients. PLoS One 9, e94794
(2014).
5.
Calabresi, P. a et al. The incidence and significance of anti-natalizumab antibodies. Neurology 69, 1391–1403 (2007).
6.
Vennegoor, A. et al. Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis. Mult. Scler. 19, 593–
600 (2013).
7.
Lundkvist, M. et al. Characterization of anti-natalizumab antibodies in multiple sclerosis patients. Mult. Scler. 19, 757–64 (2013).
8.
Axtell, R. C. et al. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat. Med.
16, 406–12 (2010).
9.
Hartung, H.-P. et al. Interleukin 17F level and interferon β response in patients with multiple sclerosis. JAMA Neurol. 70, 1017–21 (2013).
10.
Hecker, M. et al. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int. J. Mol. Sci.
14, 16087–110 (2013).
11.
De Felice, B. et al. Small non-coding RNA signature in multiple sclerosis patients after treatment with interferon-β. BMC Med. Genomics 7, 26 (2014).
12.
Bloomgren, G. et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N. Engl. J. Med. 366, 1870–80 (2012).
13.
Plavina, T. et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal
leukoencephalopathy. Ann. Neurol. 76, 802–12 (2014).
14.
Schwab, N. et al. L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients. Neurology 81, 865–71 (2013).
15.
Villar, L. M. et al. lipid-specific IgM bands in csf associated with a reduced risk of developing pml during treatment with natalizumab. Ann. Neurol. 77,
447–57 (2015).