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

A total of 754 consecutive patients with relapsing‐remitting multiple sclerosis were investigated for interferon‐β (IFNβ) antibodies by protein‐G affinity chromatography and antiviral neutralization bioassay during 24 months on 6 MIU (22 μg) of subcutaneous IFNβ‐1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 μg) of intramuscular IFNβ‐1a once weekly (n = 140), or 8 MIU every other day of IFNβ‐1b (n = 311). The proportion of binding antibodies was higher in those receiving IFNβ‐1b compared with 6 MIU of IFNβ‐1a three times weekly (97 vs 89% at 12 months), and fewer became positive if 6 MIU of IFNβ‐1a was administered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutaneous IFNβ‐1a became positive (33 vs 58%). The binding and neutralizing capacities were higher in the IFNβ‐1b group than in the IFNβ‐1a groups; these differences, however, were not significant after 12 months. The number of positive patients varied considerably and depended on the amount of IFN added to the bioassay; adding 10 LU/ml or more masked antibody detection. Antibodies induced by either preparation neutralized both IFNβ species but not IFNα. In conclusion, IFNβ‐induced antibodies are frequently found in multiple sclerosis patients, and IFNβ‐1b is more immunogenic than IFNβ‐1a. The immunogenicity of IFNβ‐1a increases with the frequency of administration and if it is given subcutaneously. Ann Neurol 2000;48:706–712