This Article Full Text (OnlineFirst PDF) All Versions of this Article: 1352458508101946v1 15/5/601    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Google Scholar Citing Articles via Scopus Google Scholar Articles by Koch-Henriksen, N Articles by Flachs, E. Search for Related Content PubMed PubMed Citation Articles by Koch-Henriksen, N Articles by Flachs, E. Pubmed/NCBI databases Substance via MeSH Social Bookmarking                         What's this?

The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis

¹ Department of Neurology, Aarhus University Hospital in Aalborg, Denmark and The Danish MS Treatment Register, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
² Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
³ Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
⁴ National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark;

^* To whom correspondence should be addressed.

	Abstract

Objective

To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFN) depends on the type of IFN (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS).

Introduction

NAbs against IFN-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFN-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs.

Design/patients

All Danish MS-patients who had started first-time treatment with IFN-1a 22 µg s.c tiw (Rebif22) or IFN-1b 250 µg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit.

Methods

We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFN-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable.

Results

In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 (P = 0.89) and of time (P = 0.80).

Conclusion

NAbs caused by IFN-1a s.c. do not differ from NAbs caused by IFN-1b in their detrimental clinical effect.

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

First published on March 19, 2009, doi:10.1177/1352458508101946

Multiple Sclerosis 2009;15:601.

A more recent version of this article appeared on May 1, 2009


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