High-dose intravenous interferon-beta in multiple sclerosis patients with high-titer neutralizing antibodies (HINABS II) - A pilot study

- Interferon-beta was applied intravenously in MS patients with high neutralizing antibody titers.
- IFNβ bioavailability as measured by Myxovirus protein A was successfully established.
- A short-term decrease of NAb titers was achieved.
- Induction of tolerance towards interferon-beta, i.e. NAb reversion, was failed.

BackgroundNeutralizing antibodies (NAb) against interferon-beta (IFNβ) affect its treatment efficacy. So far, there are no anti-NAb strategies available.ObjectivesTo investigate if the repeated administration of high-dose IFNβ-1b intravenous in NAb positive multiple sclerosis (MS) patients induces tolerance and establishes IFNβ bioavailability as measured by the induction of myxovirus protein A (MxA).MethodsNine MS patients with NAb titers >500 10-fold reduction units (TRU) received 1500 μg IFNβ-1b intravenously once weekly over three months. Blood samples were collected at screening, monthly during the treatment period (before and four hours after IFNβ administration), and at follow-up after 6 months for determination of NAbs and MxA expression.ResultsMedian NAb titer at baseline was 1429 TRU. NAb titers determined before each infusion did not significantly change over the treatment period and were not different at follow-up compared to baseline. However, NAb titers were significantly decreased four hours after IFNβ infusions (by roughly 50%) and MxA mRNA levels were significantly elevated reaching a median value of 206.ConclusionsWeekly intravenous administration of IFNβ in patients with high NAb titers established its bioavailability, but failed to induce tolerance towards IFNβ.