Persistency of neutralizing antibodies depends on titer and interferon-beta preparation

Background: Neutralizing antibodies (NAbs) affect the efficacy of interferon-beta (IFN beta) treatment in multiple sclerosis (MS) patients, particularly if NAbs persist. Persistency depends on NAb titers, which differ between IFN beta preparations. Objective: This study evaluated IFN beta 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 IFN beta 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 IFN beta-1a and by 60% in the IFN beta-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 IFN beta-1a group, whereas titers of >460 NU had a sensitivity of 100% and a specificity of 91.7% in the IFN beta-1b group to predict persistency at follow-up. When these cut-off titers are applied, 10.2% of all treated patients developed persistent NAbs. Conclusion: IFN beta preparation-specific NAb cut-off titers for prediction of NAb persistency, which may be useful in individual treatment decision making, are provided.