Background: Neutralizing antibodies (NAb) against interferon-beta (IFNβ) affect its treatment efficacy. So far, there are no anti-NAb strategies available.

Objective: To 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).

Methods: Nine MS patients with NAb titers >500 10-fold reduction units (TRU) received 1500μg 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.

Results: Median NAb titer at baseline was 1429TRU. 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.

Conclusions: Weekly intravenous administration of IFNβ in patients with high NAb titers established its bioavailability, but failed to induce tolerance towards IFNβ.