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NABs should be measured in all patients treated with IFN-beta. If patients have been persistently NAB-negative for 24 months, measurements can be discontinued. Patients who have been NAB-positive for a period of 18 months or more usually remain NAB-positive for a long time.

A total of 754 consecutive patients with relapsing-remitting multiple sclerosis were investigated for interferon-beta (IFNbeta) antibodies by protein-G affinity chromatography and antiviral neutralization bioassay during 24 months on 6 MIU (22 microg) of subcutaneous IFNbeta-1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 microg) of intramuscular IFNbeta-1a once weekly (n = 140), or 8 MIU every other day of IFNbeta-1b (n = 311). The proportion of binding antibodies was higher in those receiving IFNbeta-1b compared with 6 MIU of IFNbeta-1a three times weekly (97 vs 89% at 12 months), and fewer became positive if 6 MIU of IFNbeta-1a was administered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutaneous IFNbeta-1a became positive (33 vs 58%). The binding and neutralizing capacities were higher in the IFNbeta-1b group than in the IFNbeta-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 IFNbeta species but not IFNalpha. In conclusion, IFNbeta-induced antibodies are frequently found in multiple sclerosis patients, and IFNbeta-1b is more immunogenic than IFNbeta-1a. The immunogenicity of IFNbeta-1a increases with the frequency of administration and if it is given subcutaneously.

Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb) by protein-G affinity-chromatography radioimmunoassay and a commercially available enzyme immunoassay (EIA). Neutralizing antibody (NAb) was investigated by cytopathic effect assays (CEA) using both fixed amount and serially diluted sera. BAb correlated with log10-transformed titres obtained by EIA (r=0.70, P<0.0001); the latter, however, failed to demonstrate low-level BAb. Comparison of clinical significance of NAb-positivity measured by biological assays with different sensitivities demonstrated an optimal odds ratio for relapse rate using 10 laboratory units (LU)/mL. Purification of IgG prior to CEA removed toxicity from toxic sera. The neutralizing capacity data correlated linearly with logl0-transformed titres obtained by a Kawade 10-to-1 LU/mL CEA (r=0.77, P<0.0001). In conclusion, neutralizing capacity CEA utilizing a fixed amount of serum predicts differences in relapse rates in IFNbeta-treated MS patients and correlates with NAb titres of the 10-to-1 LU/mL CEA. Neutralizing capacity CEA is less laborious and more economical than titre-based NAb assays and suitable for large-scale screenings of MS patients.