Neutralising and binding anti-interferon-beta-1b (IFN-beta-1b) antibodies during IFN-beta-1b treatment of multiple sclerosis

Interferon-beta-lb (IFN-beta-lb) is on immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-beta-lb could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-beta-lb for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-beta-lb antibodies, presently not believed to impede the clinical efficacy of IFN-beta-lb, were demonstrated by on immunoassay in some patients already after 1 month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be on early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-beta-la and natural IFN-beta were also found in a majority of IFN-beta-lb treated Patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay 68% of MS patients treated with IFN-beta-lb for 1-23 months had elevated numbers of anti-IFN-beta-lb-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-beta-lb is immunogenic in MS patients. High levels of anti-IFN-beta-lb antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-beta-lb antibodies might also occur spontaneously.