Thursday, 27 September 2012

Research:Neutralizing Antibodies with Tysabri

BACKGROUND: Antibodies against natalizumab have been found in 4.5-14.1% of natalizumab-treated multiple sclerosis (MS) patients. If antibodies persist, they are associated with an adverse effect on treatment response. However, it has proved to be difficult to standardize anti-drug antibody measurements.
OBJECTIVES: The purpose of this study was to evaluate the clinical and radiological impact of serum natalizumab concentrations and their relation with anti-natalizumab antibodies in MS patients.
METHODS: In this prospective observational cohort study of 73 consecutive patients treated with natalizumab, we measured serum natalizumab levels and antibody titers before the start of natalizumab treatment, at weeks 12 and 24 and annually after natalizumab initiation. Antibodies against natalizumab were measured by radioimmunoassay and serum natalizumab concentrations using a newly developed enzyme linked immunosorbent assay (ELISA). Magnetic resonance imaging (MRI) scan and clinical evaluation were performed before the start of natalizumab treatment and subsequently every year.
RESULTS: Antibodies were detected in 58% of the natalizumab-treated patients. All patients developed their antibodies before week 24. The large majority of these patients reverted to neutralizing antibody (NAb) negative status during follow-up. The presence of antibodies was inversely correlated with serum natalizumab concentration (p<0.001). Only high antibody titers (titre=amount) are associated with very low or undetectable serum natalizumab concentration. Both high antibody titers and low serum natalizumab concentrations are associated with relapses and gadolinium-enhancing lesions on MRI.
CONCLUSIONS: Our data show that both low natalizumab serum concentration and high antibody titers are associated with a lack of efficacy of natalizumab. Measuring serum natalizumab, using a highly specific assay, might lead to more enhanced precision using natalizumab in individual patients.

Just as Nabs can occur with beta interferon injections, they can an probably willl occur with any protein that is injected. This occurs as shown here with tysabri and it can even happen with Alemtuzumab. The increase in antibodies against the injection proteins can cause injection reactions. If they bind to the active site they are neutralizing and stop the protein drug working. This occurs with tysabri infusion and is common but it appears you need a high amount of the antibody (titre) in the blood for it to stop tsabri working and then you get disease break through and it is time to think about changing your treatment.


  1. Are Tysabri Antibody titers the same as JC Virus titers?

    If one tests negative for Tysabri Antibody titers, can s/he still have JC Virus?

  2. No Tysabri antibody titres means levels of antibodies against tysabri..i.e.if you have these the tysabri may stop working or you can get allergic reactions on infusion.

    JC virus tires means the levels of JC virus in the blood by anti-JC virus titres which I think you mean is the level (titre) of antibodies that are reactive to JC virus. Having an anti JC virus titre means you have immunity to JC virus which is kind of a good thing good thing.

    However it also means you have seen JC virus because you have been infected at some time and therefore you have a risk of PML as the virus can be dormant and become infective again when tysabri stops the immune response

    1. Ideally you will be anti JC virus negative and anti tysabri negative i.e have no antibody tires to either


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