“Tysabri® can only be given for 2 years.” – I hear this sentence quite often, and it is definitely not correct! Natalizumab can ultimately be given lifelong, or – perhaps more realistically formulated – Tysabri® can be given as long as the doctor and patient are convinced of the effectiveness of the drug and are willing to bear the risk of potential side effects. From a medical-scientific point of view, this means – as long as a careful benefit-risk assessment speaks for the administration of the drug.
Natalizumab (Tysabri®) is probably known to most MS patients. It was the first monoclonal antibody approved in 2006 for the treatment of relapsing MS. In terms of its effectiveness, this drug was a breakthrough. It is one of the most effective drugs we have available and there are – from my own experience – few patients who do not benefit from this therapy.
But as is often the case in medicine – this very good effectiveness does not come for free. The administration of Natalizumab, which has hardly any side effects and tolerability problems, is associated with an increased risk of progressive multifocal leukoencephalopathy (PML) – a viral infection of the brain, which I have written about often in this blog.
PML is a fundamental but very rare risk with all immunotherapies that can occur in individual cases. However, under Natalizumab therapy, a systematic occurrence of PM must be expected, which can be quantified – based on the total number of patients – at approximately 1: 250 – 1:500. This means that although it is a rare but ultimately serious and serious side effect, as PML can cause serious damage.
Therefore, it was very important – and still is – to identify factors associated with an increased risk of this serious side effect. The most important factor is whether one has ever had contact with the JC virus (causes PML), because – to put it simply – if one does not carry the virus, one cannot get PML.
To clarify whether one has ever been infected with the JC virus in one’s life, the body’s own antibodies against the virus are determined. If one has had contact, the antibody titer is positive; if not, one is negative – and in negative patients, the risk of developing a PML under Natalizumab is extremely low.
It is – but it must be said – not equal to zero. Therefore, negative patients must definitely be watched. Also, it should be regularly checked whether the antibody titer remains negative, because one can also get infected with the virus under Natalizumab therapy. In any case, one can – to come back to the initial question – treat JCV negative patients with Natalizumab for longer than two years. And this should be done as long as a satisfactory effect is achieved – and from my own experience, this can be the case for many, many years.
The situation is different for JCV-antibody positive patients. They have a PML risk in the order of magnitude given above. It has been observed that when the PML risk is plotted against the duration of therapy, the risk of PML is relatively low, especially in the first, but also in the second year of therapy. After the second year of therapy, however, the risk increases significantly and is then approximately 1:200. If one has previously had classical immunosuppressive therapy (e.g., Mitoxantrone or Azathioprine), the risk can even rise to approximately 1:90.
Because of this risk increase after two years, it has somehow become ingrained in many people’s minds that one “has to” stop Natalizumab in JCV-antibody positive patients after two years. But this statement is false. The correct approach in this case is a rational benefit-risk analysis, which one should perform together with one’s patient. Nowadays, patients are usually treated with Natalizumab who have had a severe course of MS and need a strong drug to control the disease. Many of these patients are willing to bear the above-mentioned risk if they have experienced a high level of disease activity and how they feel with the drug. Then the treating physician should also support this wish. However, there are also cases where the patient fears such a risk – then it is correct to end the therapy. So ultimately, the duration of a Natalizumab therapy is largely determined by the patient’s perception of risk and his or her personal benefit-risk assessment. If you stop Natalizumab therapy, it is crucial to offer an adequate alternative for the time afterwards. What options are available, I will discuss in one of the next articles.
