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Myxovirus Resistance Protein A mRNA Expression Kinetics in Multiple Sclerosis Patients Treated with IFNβ

J. Libertinova, E. Meluzinova, A. Tomek, D. Horakova, I. Kovarova, V. Matoska, S. Kumstyrova, M. Zajac, E. Hyncicova, P. Liskova, E. Houzvickova, L. Martinkovic, M. Bojar, E. Havrdova, P. Marusic,

. 2017 ; 12 (1) : e0169957. [pub] 20170112

Language English Country United States

Document type Clinical Trial, Journal Article

Persistent link   https://www.medvik.cz/link/bmc17031136

INTRODUCTION: Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value. METHODS: A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values. RESULTS: 119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mRNA expression levels between baseline and month three. Using survival analysis, none of the selected baseline MxA mRNA cut off points allowed prediction of time to first relapse on the treatment. In NAb negative patients, mean MxA mRNA levels did not significantly differ in patients irrespective of relapse status. CONCLUSION: Baseline MxA mRNA does not predict the response to IFNß treatment or the clinical status of the disease and the level of MxA mRNA does not correlate with disease activity in NAb negative patients.

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$a INTRODUCTION: Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value. METHODS: A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values. RESULTS: 119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mRNA expression levels between baseline and month three. Using survival analysis, none of the selected baseline MxA mRNA cut off points allowed prediction of time to first relapse on the treatment. In NAb negative patients, mean MxA mRNA levels did not significantly differ in patients irrespective of relapse status. CONCLUSION: Baseline MxA mRNA does not predict the response to IFNß treatment or the clinical status of the disease and the level of MxA mRNA does not correlate with disease activity in NAb negative patients.
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$a Meluzinova, Eva $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Tomek, Ales $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Horakova, Dana $u Department of Neurology and Center of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
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$a Kovarova, Ivana $u Department of Neurology and Center of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
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$a Matoska, Vaclav $u Laboratory of Molecular Diagnostics, Na Homolce Hospital, Prague, Czech Republic.
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$a Kumstyrova, Simona $u Laboratory of Molecular Diagnostics, Na Homolce Hospital, Prague, Czech Republic.
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$a Zajac, Miroslav $u Department of Medical Microbiology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Hyncicova, Eva $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Liskova, Petra $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Houzvickova, Eva $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Martinkovic, Lukas $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Bojar, Martin $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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$a Havrdova, Eva $u Department of Neurology and Center of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
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$a Marusic, Petr $u Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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