Biologic impact of interferon antibodies, and complexities in assessing their clinical significance.

The relevance of neutralizing antibodies (NAb) to interferon-beta (IFNbeta) for patients with MS treated with IFNbeta injections has been controversial. Published data from several double-blind, randomized clinical trials demonstrate that disease activity in IFNbeta-treated patients with MS is similar to placebo-treated patients within the same study. This observation is easily understood by other studies that demonstrate attenuation of the biologic response to IFNbeta injections in patients who are NAb positive. Because of the period over which antibodies develop, however, studies will demonstrate an impact of IFNbeta NAb only after the initial 18 months of therapy. Further, because the effects of IFNbeta on MS disease activity and progression are partial, large sample sizes are required to demonstrate clinical correlates of NAb. Therapeutic decisions related to disease management for patients with MS must consider IFNbeta NAb.