Research:Neutralizing Antibodies with Tysabri

EpubVennegoor et al. Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis. Mult Scler. 2012 Sep 19.

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.

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