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

Clinical Department of Neurology, Innsbruck Medical University, Austria

D Rudzki

Clinical Department of Neurology, Innsbruck Medical University, Austria

M Hölzl

Clinical Department of Neurology, Innsbruck Medical University, Austria

R Ehling

Clinical Department of Neurology, Innsbruck Medical University, Austria

C Gneiss

Clinical Department of Neurology, Innsbruck Medical University, Austria

B Künz

Clinical Department of Neurology, Innsbruck Medical University, Austria

T Berger

Clinical Department of Neurology, Innsbruck Medical University, Austria

M Reindl

Clinical Department of Neurology, Innsbruck Medical University, Austria

F Deisenhammer

Clinical Department of Neurology, Innsbruck Medical University, Austria florian.deisenhammer{at}i-med.ac.at

Background

Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS.

Methods

NAB-positive patients with MS were treated with 8 MIU IFNβ-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 IFNβ 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 IFNβ-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 IFNβ can restore bioavailability of IFNβ in patients with NABs.

Key Words: beta-interferon • immunology • multiple sclerosis • outcome measurement

This version was published on August 1, 2009

Multiple Sclerosis, Vol. 15, No. 8, 977-983 (2009)
DOI: 10.1177/1352458509105384


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