High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study

BACKGROUND: Neutralizing antibodies (NABs) against interferon beta (IFNbeta) are associated with a loss of IFNbeta bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNbeta-1b can restore bioactivity in NAB-positive patients with MS. METHODS: NAB-positive patients with MS were treated with 8 MIU IFNbeta-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee. RESULTS: Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12-3234) and RNA (2186, range 114-7525) area under the curve levels for the four measurements at each IFNbeta injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0-2709) for MxA protein after 8 MIU i.v. and 254 (0-1200) after s.c., and 1763 (25-7188) for MxA RNA after 8 MIU i.v., and 557 (5-2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNbeta-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed. DISCUSSION: The results indicate that i.v. administration of IFNbeta can restore bioavailability of IFNbeta in patients with NABs.