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Mult Scler. 2013 May;19(6):757-64. doi: 10.1177/1352458512462920. Epub 2012 Oct 8.

Characterization of anti-natalizumab antibodies in multiple sclerosis patients.

Author information

1
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

BACKGROUND:

A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies.

OBJECTIVE:

The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients.

METHODS:

Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1-4 antibodies using ELISA and ImmunoCAP®.

RESULTS:

Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time.

CONCLUSIONS:

The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1-4 antibodies could be used to discriminate between transiently and persistently positive patients.

KEYWORDS:

Anti-drug antibody; multiple sclerosis; natalizumab

PMID:
23045379
DOI:
10.1177/1352458512462920
[Indexed for MEDLINE]

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