Abstract

Ross C, Clemmesen KM, Svenson M, Sorensen PS, Koch-Henriksen N, Skovgaard GL, Bendtzen K. Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann Neurol 2000;48:706-712.

A total of 754 consecutive patients with relapsing-remitting multiple sclerosis were investigated for interferon-beta (IFN-beta) antibodies by protein-G affinity chromatography and antiviral neutralisation bioassay during 24 months on 6 MIU (22 microg) of subcutaneous IFN-beta-1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 microg) of intramuscular IFN-beta-1a once weekly (n = 140), or 8 MIU every other day of IFN-beta-1b (n = 311). The proportion of binding antibodies was higher in those receiving IFN-beta-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 administered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutaneous IFN-beta-1a became positive (33 vs 58%). The binding and neutralising 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. 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 neutralised 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.