PML risk higher than expected. Why? #ClinicSpeak #MSBlog #MSResearch
"The following commentary suggests that the PML risk on natalizumab is higher than the Biogen figures. Why? I am sure this relates to the denominator and have discussed this before many times. People with MS who are JCV negative should be excluded from the risk ratio. At present the denominator includes all pwMS on natalizumab (JVC+ve and JCV-ve) subjects. As we derisk people by taking them off natalizumab the number of JCV+ve people in the denominator is going down. Therefore the current methods for calculating PML risk is underestimating the risk. This is why we have made a decision to get all of our JCV+ve patients off natalizumab. What has changed is that we now have other treatment options. In the past we didn't have other options; therefore why take unnecessary risks? Despite this we have some patients who have done so well on natalizumab is that they are reluctant to switch treatments. What I do in this situation is tell them that if their anti-JCV index goes up by more than 10% it indicates that their virus is active and boosting their immune system and if they want to avoid getting PML they must come off natalizumab. Please remember the process of developing PML is very complex; the JCV virus has to acquire many mutations to be able to cause PML. It is unlikely that when you stop natalizumab that these processes unwind themselves. This means you will carry some of your PML risk with you when you switch to other therapies. This is important when you move over to any treatment that suppresses your immune system. This is why we are going to see increasing number of ex-natalizumabers developing PML on other follow-on drugs."
The risk algorithm for natalizumab-associated PML was first established in 2012 using the observations that JC virus antibody status, prolonged duration of natalizumab therapy (>2 years), and prior exposure to immunosuppressive therapy increased the risk for the disease. Prior to the publication of Biogen's algorithm, a risk algorithm was created by Fox and Rudick using an Excel spreadsheet in order to address the concerns of their patients. Applying the most recently available data regarding natalizumab-associated PML, the risk assessments for PML were recalculated. The current numbers indicate substantially higher risks for PML in 2015 than in 2012. Our calculations suggest that an individual having all three risk factors has an approximately 1 in 44 chance of developing PML.