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.


CONCLUSIONS
The results indicate that i.v. administration of IFNbeta can restore bioavailability of IFNbeta in patients with NABs.
Millonig
A
A
Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Rudzki
D
D
Hölzl
M
M
Ehling
R
R
Gneiss
C
C
Künz
B
B
Berger
T
T
Reindl
M
M
Deisenhammer
F
F
D000328:Adult; D000906:Antibodies / Q000097:blood*; D001682:Biological Availability; D004185:Disability Evaluation; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D009460:Neurologic Examination; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000906:Antibodies; D007155:Immunologic Factors; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012367:RNA, Viral; D000068576:Interferon beta-1b; D016899:Interferon-beta; D019204:GTP-Binding Proteins