Are there studies proving the Tysabri PML “Risk Factor” is reduced by extending dosing intervals to 8 weeks or more?

Here is My Question:
Are there studies proving the Tysabri PML “Risk Factor” is reduced by extending dosing intervals to 8 weeks or more?

I selfishly ask: I was JC positive when starting Tysabri 8/2006. I had 132 TOTAL infusions 8/2006 to 5/2018 including 2 "Breaks" Break #1 was 7/2008 for 3 months, restarted 10/2008; #2 was 11/2011 for 8 months, restarted 7/2012. 

Break #2 was originally planned as permanent because 7/2012 LP found JCV antibodies in my CSF. I accepted risks compared to personal benefits from treatment and restarted Tysabri 7/2012. Last LP and CSF test 7/2013 was “normal.” Six month Tysabri protocol MRI’s show little change; symptoms stable and no flare ups. 

Began 5 week intervals in 2017 and 6 week intervals in 2018. JC titer range .5 to .8 through 1/2018. However “titer risk” increased 5/2018 to 1.25 and 10/2018 to 1.68. With more than 72 months of treatments and titers of 1.25 and 1.68 the “Risk Factor” table* shows PML risk of 1 in 333 and 1 in 100 respectively. SO…..

--Are the only tested and reliable risk tables based on frequency of treatments every 4weeks (13x annually) ?
--Has Biogen or any trustworthy entity created a “Risk Index” for PML with Tysabri on extended dosing of 6, 8 or greater week intervals? 

I know risk of PML greater w/Tysabri than Rituxan/Ocrelus.(Lemtrada ruled out).But I’m scared of changing from Tysabri, that’s worked to a new treatment with new risks. Any and all suggestions, comments, references and ideas welcome. 

Answer:
I will refer the author of this question to a research abstract from ACTRIMS meeting earlier this year which addresses risk for PML among JCV antibody POSITIVE patients among standard dosing (4 weeks) and extended dosing (more than 4 weeks but less than 12 weeks):

https://actrims.confex.com/actrims/2018/meetingapp.cgi/Paper/3102

The study analyzed Biogen’s TOUCH Program database.  Hazard risk for PML among extended dose patients was much lower and statistically significant compared to standard dosing.

I am not aware of a separate risk table for extended dosing patients.  While this study cannot evaluate the effectiveness of extended dosing on disease activity, this has been reported at numerous scientific conferences including this month at ECTRIMS:

https://www.neurologyadvisor.com/ectrims-2018/natalizumab-extended-dosing-schedule-multiple-sclerosis-treatment-efficacy/article/806221/

Even with this welcomed data and the observation that extend dose interval confers lower PML risk without sacrificing disease control, the decision to continue on therapy must be discussed with the treating physician.  

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente