I am JCV positive...will a 6 or 8 week dosing interval with Tysabri be OK?

Here is My Question:
Hello, I am JCV positive and have been assured that a 6/8 week interval between each Tysabri is not dangerous as far as developing PML goes, would you agree?

Answer:
You ask for assurance that something is not "dangerous". Dangerous is a loaded term, especially in medicine. We prefer to compare risk with benefit, the so-called risk/benefit ratio and allow people to make their own decision. So here are the facts as we know it.

1. There have only been 15 cases of PML associated with the use of Tysabri since 2012. PML is now a rare occurrence in individuals treated with Tysabri. There are several reasons for the dramatic reduction in PML cases over the past 10 years. These include better education of clinicians prescribing Tysabri and monitoring people with MS on this drug, reducing the number of at-risk people with MS prescribed Tysabri (especially people with JCV Index > 1.5 or with a history of prior immunosuppression), and extending the dosing interval from 4 weeks to 6 or 8 weeks in people with elevated JCV index.
2. There is good data supporting extended interval dosing of Tysabri to reduce the risk of PML. A retrospective analysis of US anti-JCV antibody positive Tysabri treated patients from the TOUCH registry compared the risk of PML in people with MS treated every 4 weeks (28 days) to the risk in people with MS treated with extended interval dosing as identified in the last 18 months of treatment (average dosing intervals in this group was approximately 6 weeks). The majority (85 %) of people with MS who were in the extended interval dosing group had already received monthly dosing for at least a year prior to switching to extended interval doing. An updated analysis showed a 88 % reduction in the risk of PML in people with MS switched to extended interval dosing. This study did not determine if extending the interval between infusions was effective.
3. Several retrospective case control studies reported no significant loss of efficacy when people are switch from standard dosing (every 28 days) to extended interval dosing ranging from 6 to 8 weeks between infusions. Biogen, the maker of Tysabri, announced the results of their NOVA study in August 2021.  This was a randomized, controlled study of 499 people with MS comparing the efficacy of continuing every 4-week Tysabri infusions or switching to every 6- week infusions. There was no meaningful difference in clinical or MRI outcomes between the two groups. Approximately 97 % of patients in both treatment groups remained relapse free after 72 weeks. One patient in the 6-week dosing interval arm of the study developed asymptomatic PML. While the results of the Biogen study have not yet been published in a peer reviewed journal, they are consistent with prior uncontrolled study results. The NOVA study also highlights the importance of continuing to monitor for PML regardless of dosing interval, since the disease is rarely fatal if detected while asymptomatic and confined to one lobe of the brain in people on Tysabri.

Lastly, it is always important to emphasize that all treatments for MS have potentially severe risks. These risks are generally manageable if patients and physicians follow accepted protocols for mitigating these risks. Not adhering to agreed upon dosing schedules, missing visits, forgetting to monitor blood work or failure to monitor MRI scans are all recipes for unsatisfactory and rarely, "dangerous" outcomes.

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego