Are ex vivo neutralising antibodies against IFN-beta always detrimental to therapeutic efficacy in multiple sclerosis?

¹ Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
² Department of Neurology, Aalborg Hospital, Aalborg, Denmark and The Danish MS Treatment Register, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
³ Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

^* To whom correspondence should be addressed.

	Abstract

Neutralising antibodies (NAbs) against interferon (IFN)-beta reduce the treatment effect in multiple sclerosis (MS). However, data from pivotal trials of IFN-beta in MS suggest that NAb-positive patients may have a reduced relapse rate during the first six to 12 months of therapy. We collected clinical data and plasma samples for NAb measurements prospectively, every six months, in 468 patients treated with the same IFN-beta preparation for at least 24 months. NAbs were measured blindly with a cytopathic effect (CPE) assay. During treatment months 0-6, patients who became NAb-positive had significantly fewer relapses compared to patients who maintained the NAb-negative status, whereas the opposite was observed after month 6. This is in accordance with observations in randomised studies of the three different IFN-beta preparations, showing that patients who become NAb-positive have lower relapse rates during the first six or 12 months of therapy. We hypothesise that low affinity NAbs, present early after the start of IFN-beta therapy, though neutralising in vitro in sensitive assays increase the half-life of IFN-beta in vivo and, thereby, enhance the therapeutic effect. With affinity maturation, NAbs effectively prevent IFN-beta binding to its receptors also in vivo and, hence, abolish the treatment effect.

Key Words: binding antibodies, interferon-beta, multiple sclerosis, neutralising antibodies, therapy, treatment effect

First published on February 9, 2007, doi:10.1177/1352458506072344

Multiple Sclerosis 2007;13:616.

A more recent version of this article appeared on June 1, 2007


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