Persistency of neutralizing antibodies depends on titer and interferon-beta preparation.
BACKGROUND
Neutralizing antibodies (NAbs) affect the efficacy of interferon-beta (IFNβ) treatment in multiple sclerosis (MS) patients, particularly if NAbs persist. Persistency depends on NAb titers, which differ between IFNβ preparations.


OBJECTIVE
This study evaluated IFNβ preparation-specific NAb cut-off titers during early treatment for prediction of NAb persistency.


METHODS
Patients who had at least one NAb test between 12 and 30 months (baseline) as well as after more than 48 months (follow-up) on IFNβ treatment were included in this longitudinal study.


RESULTS
At baseline 1064 patients had a NAb test. Of those, 203 had a follow-up test. In the follow-up group 23.2% of patients were NAb positive during baseline. NAb frequency significantly decreased by 40.7% in the IFNβ-1a and by 60% in the IFNβ-1b group at follow-up after a mean time of 75.4 months on treatment, and median NAb titers decreased significantly in both groups. During baseline, NAb titers of >258 neutralizing units (NU) had a sensitivity of 81.3% and a specificity of 90.9% in the IFNβ-1a group, whereas titers of >460 NU had a sensitivity of 100% and a specificity of 91.7% in the IFNβ-1b group to predict persistency at follow-up. When these cut-off titers are applied, 10.2% of all treated patients developed persistent NAbs.


CONCLUSIONS
IFNβ preparation-specific NAb cut-off titers for prediction of NAb persistency, which may be useful in individual treatment decision making, are provided.
Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Harald
H
Hegen
Manuel
M
Schleiser
Claudia
C
Gneiss
Franziska
F
Di Pauli
Rainer
R
Ehling
Bettina
B
Kuenz
Andreas
A
Lutterotti
Thomas
T
Berger
Florian
F
Deisenhammer
D057134:Antibodies, Neutralizing / Q000097:blood*; D001317:Austria; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
D057134:Antibodies, Neutralizing; D007155:Immunologic Factors; D016899:Interferon-beta