Premium
Lack of interferon‐beta bioactivity is associated with the occurrence of relapses in multiple sclerosis
Author(s) -
Van Der Voort L. F.,
Visser A.,
Knol D. L.,
Oudejans C. B. M.,
Polman C. H.,
Killestein J.
Publication year - 2009
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2009.02649.x
Subject(s) - medicine , multiple sclerosis , biomarker , interferon , messenger rna , interferon beta , immunology , biological drugs , disease , pharmacology , gene , biology , biochemistry
Background: Treatment failure to Interferon‐beta (IFNβ) in multiple sclerosis (MS) can only partly be explained by anti‐IFNβ neutralising antibodies (NAb). Myxovirus resistance protein A (MxA) mRNA, reflecting IFNβ bioactivity, is studied as an alternative biomarker for IFNβ therapy response. Although absent IFNβ bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNβ bioactivity and clinical disease activity is largely unknown. Methods: We enrolled 126 consecutive relapsing‐remitting MS patients on IFNβ treatment. MxA mRNA expression was assessed 4 h after IFNβ injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNβ injection). Patients were considered biological non‐responders when both MxA mRNA expression and MxA mRNA induction were negative. Results: Biological non‐responders showed a significantly higher annualised relapse rate and smaller proportion relapse‐free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%). Conclusions: Our results suggest that a lack of IFNβ bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNβ.