Immunogenicity of interferon-beta in multiple sclerosis patients: Influence of preparation, dosage, dose frequency, and route of administration

A total of 754 consecutive patients with relapsing-remitting multiple scler osis were investigated for interferon-p (IFN beta) antibodies by protein-G affinity chromatography and antiviral neutralization bioassay during 24 mon ths on 6 MIU (22 mug) of subcutaneous IFN beta -1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 mug) of intramuscular IFN beta -1a once weekly (n = 140), or 8 MIU every other day of IFN beta -1a (n = 311). The proportion of binding antibodies was higher in those receiving IFN bet a -1b compared with 6 MIU of IFN beta -1a three times weekly (97 vs 89% at 12 months), and fewer became positive if 6 MIU of IFN beta -1a was administ ered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutan eous IFN beta -1a became positive (33 vs 58%). The binding and neutralizing capacities were higher in the IFN beta -1b group than in the IFN beta -1a groups; these differences, however, were not significant after 12 months. T he number of positive patients varied considerably and depended on the amou nt of IFN added to the bioassay; adding 10 LU/ml or more masked antibody de tection, Antibodies induced by either preparation neutralized both IFN beta species but not IFN alpha. In conclusion, IFN beta -induced antibodies are frequently found in multiple sclerosis patients, and IFN beta -1b is more immunogenic than IFN beta -1a, The immunogenicity of IFN beta -1a increases with the frequency of administration and if it is given subcutaneously.