Development of Neutralizing Antibodies in Patients with Relapsing-Remitting Multiple Sclerosis Treated with IFN-β1a

Sixty-eight patients with relapsing-remitting multiple sclerosis (RRMS) were treated with 3 million or 9 million i.u. of recombinant interferon-beta1a (recIFN-beta1a) s.c. three times a week for 2 years. Their sera were tested for antibodies neutralizing the IFN (NAb) in a bioassay. Sera with titers > or = 1:20 were considered positive. We detected NAb in 3.2%, 13.8%, and 15.9% of the patients in sera obtained at 3, 6, and 24 months, respectively. The incidence was not related to the IFN dose. Interestingly, during the 6 month baseline period before the start of the study, relapse rates, baseline disability, and the volume of lesions on T2-weighted images were significantly higher in patients who developed NAb during treatment. Because of interpatient variability, no definitive relationship was observed between NAb formation and loss of clinical or magnetic resonance imaging (MRI) response.

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