Prediction of antibody persistency from antibody titres to natalizumab

Mult Scler. 2012 Oct;18(10):1493-9. doi: 10.1177/1352458512441688. Epub 2012 Mar 27.

Abstract

Background: In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.

Objective: To use titres of anti-natalizumab antibodies to predict persistency of antibodies.

Patients and methods: In 525 consecutive natalizumab treated patients tested for anti-natalizumab antibodies 43 (8.2%) were antibody-positive. Thirty of the antibody-positive patients, who were tested both at three and at six months after treatment start, had antibody titres in blood measured using an extended ELISA method.

Results: Samples from persistently positive patients ( N =18) had higher titre values than samples from transiently positive patients ( N =12). A cut-off value for high titre values was generated, above which patients may discontinue natalizumab therapy after three months. The method had a sensitivity of 0.83, a specificity of 1.00 and a diagnostic accuracy of 0.90.

Conclusion: An extended ELISA method for measuring anti-natalizumab antibody titres in multiple sclerosis patients on natalizumab therapy may be used for evaluation of antibody persistence. A test at three months may identify patients with high titres, who should discontinue natalizumab therapy, and patients with transient low-titre antibodies, who may continue natalizumab therapy despite development of antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Natalizumab

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Natalizumab