We thank Dr. Avasarala for the thoughtful comment on our recent article. [1] He is correct that JC virus (JCV) serology is currently the most sensitive biomarker to assess a patient's risk of developing PML during treatment with natalizumab and that patients and physicians should check for JCV serology. As noted in our article, [1] regular monitoring is recommended, as anti-JCV negative patients might convert at any time and even the index values of anti-JCV positive patients are subject to changes during treatment with natalizumab. However, many patients are anti-JCV positive even before start of therapy and, of the JCV-positive patients, most present with JCV index values of >0.9. Therefore, while the biomarker is extremely sensitive, its specificity prevents it from being an exclusion criterion. Furthermore, if the biomarker cannot be used as an exclusion criterion, it would be difficult to force patients or physicians to use it in daily clinical practice. It should, of course, be available to every patient and every physician should counsel their patients accordingly, but it seems unwise to force a biomarker with such little specificity on patients.
As suggested by Dr. Avasarala, a database with the JCV serostatus of all known PML cases would be a valuable resource for researchers.
We do not yet understand the biological background of the changes reported in our article and, after talking with colleagues around the world, we found that while many see similar trends, there are a few patient cohorts without these developments. It is a task for future studies to elucidate the influence of virus-host connections and environmental factors on the development of anti-JCV antibodies and, subsequently, of PML. We hope to contribute more to this important topic in the coming years.
1. Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm 2016;3:e195.
For disclosures, please contact the editorial office at nnnjournal@neurology.org.
We thank Dr. Avasarala for the thoughtful comment on our recent article. [1] He is correct that JC virus (JCV) serology is currently the most sensitive biomarker to assess a patient's risk of developing PML during treatment with natalizumab and that patients and physicians should check for JCV serology. As noted in our article, [1] regular monitoring is recommended, as anti-JCV negative patients might convert at any time and even the index values of anti-JCV positive patients are subject to changes during treatment with natalizumab. However, many patients are anti-JCV positive even before start of therapy and, of the JCV-positive patients, most present with JCV index values of >0.9. Therefore, while the biomarker is extremely sensitive, its specificity prevents it from being an exclusion criterion. Furthermore, if the biomarker cannot be used as an exclusion criterion, it would be difficult to force patients or physicians to use it in daily clinical practice. It should, of course, be available to every patient and every physician should counsel their patients accordingly, but it seems unwise to force a biomarker with such little specificity on patients.
As suggested by Dr. Avasarala, a database with the JCV serostatus of all known PML cases would be a valuable resource for researchers.
We do not yet understand the biological background of the changes reported in our article and, after talking with colleagues around the world, we found that while many see similar trends, there are a few patient cohorts without these developments. It is a task for future studies to elucidate the influence of virus-host connections and environmental factors on the development of anti-JCV antibodies and, subsequently, of PML. We hope to contribute more to this important topic in the coming years.
1. Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm 2016;3:e195.
For disclosures, please contact the editorial office at nnnjournal@neurology.org.