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Myxovirus Resistance Protein A mRNA Expression Kinetics in Multiple Sclerosis Patients Treated with IFNβ
Jana Libertinova1, Eva Meluzinova1, Ales Tomek1
1Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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.
Insights
Baseline Myxovirus resistance protein A (MxA) mRNA levels do not predict treatment response or clinical status in multiple sclerosis patients receiving interferon-beta (IFNß). MxA mRNA levels also do not correlate with disease activity in patients without neutralizing antibodies.
Area of Science:
- Neuroimmunology
- Pharmacogenomics
Background:
- Interferon-beta (IFNß) is a primary therapy for relapsing-remitting multiple sclerosis (MS).
- Myxovirus resistance protein A (MxA) mRNA indicates IFNß bioactivity, potentially affected by neutralizing antibodies (NAbs).
Purpose of the Study:
- To investigate MxA mRNA expression kinetics during long-term IFNß treatment in MS patients.
- To evaluate the predictive value of baseline MxA mRNA for treatment response and clinical outcomes.
Main Methods:
- Prospective, observational study of 107 MS patients initiating IFNß therapy.
- MxA mRNA and NAbs were measured periodically; relapses were tracked over 24 months.
- Correlation analysis between baseline MxA mRNA, NAb status, and disease activity.
Main Results:
- No correlation was found between baseline and 3-month MxA mRNA levels.
- Baseline MxA mRNA levels did not predict time to first relapse.
- MxA mRNA levels did not differ significantly based on relapse status in NAb-negative patients.
Conclusions:
- Baseline MxA mRNA is not a reliable predictor of IFNß treatment response or clinical status in MS.
- MxA mRNA levels do not correlate with disease activity in NAb-negative patients.
