Lately, I’ve been receiving more inquiries from Tysabri patients (active ingredient Natalizumab), who are worried about a high JCV antibody index that has been measured in them. Therefore, I would like to briefly explain what this index is about, to enable MS patients to make a realistic assessment of this value.While in the past, only positive and negative findings were differentiated, today the extent of the immune response can be determined with the help of the so-called JCV antibody index. It turned out that patients who developed progressive multifocal leukoencephalopathy (PML) (see DocBlog post on PML) during Tysabri therapy have, on average, a higher antibody index than patients who did not develop PML over the same observation period. The static analysis showed that JCV-positive patients with an index value of < 0.9 have a very low risk of PML, which is almost comparable to that of JCV-negative patients. This means that the index is primarily helpful in identifying patients who are antibody-positive but have a very low risk of PML due to the low index. With this information, it is then easier for the doctor and patient to decide about continuing therapy.
Of course, there are also many positive patients who have a higher index. For all patients with an index of > 1.5, it should be assumed that the occurrence of PML (depending on the duration of therapy) is associated with a risk of 1:100 – 1:200. This corresponds to the risk assessment that was communicated to all JCV-positive patients in the past.
In practice, if an antibody index of > 0.9 is detected, regular brain MRI scans must be performed from the 24th administration of Tysabri (i.e. after about 2 years of therapy) to detect a possible JCV infection of the brain early and discover PML in an asymptomatic stage where it usually has a good prognosis. The height of the index no longer plays a role in this recommended safety monitoring – it does not matter whether the index is 1.5 or 3.5, the consequence resulting from the values is the same.
Therefore, a “high” index of > 0.9 – in light of current knowledge – is no more reason for worry and attention than is generally appropriate for JCV-positive patients. However, for patients who are JCV-positive and have a low index, concerns about side effects can be mitigated, while of course 1) clinical vigilance is also indicated in this group and 2) regular semi-annual checks must be performed to confirm the low index – the same procedure applies as for JCV-negative patients.
Positive patients with an index > 0.9 do not need to be monitored during the course – we currently have the attitude: “positive is positive”. Furthermore, monitoring the index in patients who received immunosuppressive therapy (e.g. azathioprine, mitoxantrone, cyclophosphamide etc.) before Tysabri does not make sense. No correlation was found between the index and the occurrence of PML in this group.
It is important to me to emphasize once again that the risk assessment of a drug should not be confused with its indication. With highly active MS – and Tysabri is intended for this category – the risk of further relapses with suboptimal therapy is much greater than the risk of drug side effects. Therefore, when making therapy decisions, not only the side effects should be considered, but also the benefits of good disease control ensured by the therapy. The key point is a realistic benefit-risk assessment – and the availability of the JCV antibody index contributes to this.
