This Article Full Text (PDF) All Versions of this Article: 1352458508088942v1 14/6/837    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Google Scholar Articles by Sorensen, P. Articles by Bendtzen, K PubMed PubMed Citation Articles by Sorensen, P. Articles by Bendtzen, K Social Bookmarking                   What's this?

Is the treatment effect of IFN-β restored after the disappearance of neutralizing antibodies?

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, pss{at}rh.regionh.dk

N Koch-Henriksen

Department of Neurology, Aalborg Hospital, Aalborg, Denmark; The Danish MS Treatment Register, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

EM Flachs

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark

K Bendtzen

Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; BioMonitor A/S, Copenhagen, Denmark

Objective

To establish whether multiple sclerosis (MS) patients, who have lost the therapeutic effect of interferon-beta (IFN-β) owing to neutralizing antibodies (NAbs) and subsequently revert from a NAb-positive to a NAb-negative state under continued IFN-β-1b therapy, regain clinical effect after reversion.

Background

Several studies have shown that a significant proportion of patients treated with IFN-β develop NAbs that hamper or abolish the therapeutic effect of IFN-β. However, some patients, who become NAb-positive under treatment with IFN-β-1b, may revert to a NAb-negative state under continuous treatment.

Methods

We identified 40 patients from the Danish IFN protocol, who fulfilled the criteria: NAb-positive status for at least 12 months followed by reversion to NAb-negative state for at least 12 months. For comparison, we included 64 matching cases that had remained NAb-negative during an observation time of at least 36 months. The two groups were clinically and demographically alike. We measured NAb-neutralizing capacity using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. A patient was defined as NAb-positive after two consecutive blood tests separated by at least 6 months. Reversion to a NAb-negative state required at least two consecutive negative tests. To allow for the confounding effect of time we employed a mixed Poisson model.

Results

Patients who had been NAb-positive and reverted to a NAb-negative state regained treatment effect with the relapse rate as before the NAb-positive period adjusting for the effect of time, and the relapse rate was the same as in the permanently NAb-negative patients in corresponding time periods. The relapse rate ratio comparing the NAb-positive with the NAb-negative periods was 1.98 (95% confidence interval: 1.32–2.97).

Conclusion

Under NAb-positive periods, the clinical effect of IFN-β was abolished. When NAbs disappeared spontaneously under continued treatment, patients regained the full effect of INF-β-1b therapy with no negative carry-over effect from the previous NAb-positive period.

Key Words: interferon-beta • interferon-beta antibodies • multiple sclerosis • neutralizing antibodies • therapy • treatment effect

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Soelberg Sorensen Review: Neutralizing antibodies against interferon-beta Therapeutic Advances in Neurological Disorders, September 1, 2008; 1(2): 125 - 141. [Abstract] [PDF]