Neutralizing antibodies to natalizumab

Epub ahead of print
Jensen et al. Prediction of antibody persistency from antibody titres to natalizumab. 
Mult Scler. 2012 Mar 28.

Background: In a subgroup of MSers 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 (NABs) to predict persistency of antibodies.

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

Results: Samples from persistently positive MSers (N=18) had higher titre values than samples from transiently positive MSers (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: Measuring anti-natalizumab antibody titres in MSers on natalizumab therapy may be used for evaluation of antibody persistence. A test at three months may identify MSers with high titres, who should discontinue natalizumab therapy, and MSers with transient low-titre antibodies, who may continue natalizumab therapy despite development of antibodies.

“If you are on natalizumab it is important to be screened for these antibodies. Recommendations are for screening to be done if you have an infusion reaction and routinely at 12 and 24 months. 75% of NAB positive MSers are likely to have infusion reactions, these typically occur on the 2nd, 3rd or 4th infusion. NABs to natalizumab stop the drug working; therefore NAB+ MSers’ need to stop  the drug and switch to another therapy. I am aware that not all treatment centres are routinely measuring these antibodies; they should be. If they are not they are not using natalizumab appropriately.”

CoI: multiple

One thought on “Neutralizing antibodies to natalizumab”

  1. My experience is that neurologists do not really know that a number of MSers will develop neutralising antibodies to natalizumab. This may not be true in all countries.They were very well briefed about PML (by Biogen) but were all taken aback by the idea of antibodies against natalizumab.

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