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

Here is My Question:
Often can't put words for my thoughts. Rather than say what I want to say, I forget what or how to put speak it/the sentence/word. I have trouble mentally to force myself to slow down, doesn't help often..Some call it a brain fart. I just say I'm mental...

Answer:
Word finding or word fluency difficulty is common in MS and can result in significance pauses in thought and articulation as well as difficulty expressing oneself using proper syntax. Did you have a question about this problem?

Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
I have been on Tecifidera since 9/13 with excellent MS control. Before that I was on Tysabri for almost 7 yrs and Avonex before that.

I have always had some GI issues on Tecfidera, tremendous flatulence, intermittent diarrhea and increased reflux but they were manageable and I did not consider them to be show stoppers.

But in the past year my reflux has become so bad that I am chronically hoarse to the point where long conversations are difficult and my singing which used to be less affected than speech is impacted. Singing is really important to me. It makes me really happy and has helped a lot in controlling depression that became chronic after I had to stop working as a neonatologist. I also take venlafaxine and have periodic courses of rTMS but singing is what makes me really happy.

I have seen an ENT and there is no other vocal pathology and I am on maximal medical management including meds, diet and sleep position. Plus I have lost 40 lbs and counting.

In August, after being sick for a month with severe nausea, increased reflux, fatigue and diarrhea so severe that I soiled myself 3 times and my K went down to 2.7. I also lost 10 lbs that I have intentionally not regained. I finally had an abdominal CT that showed mesenteric panniculitis. Symptoms gradually improved without treatment other than IV fluids and temporary oral potassium. 

But I am still having flares in GI symptoms for 1-3 days at a time that interfere with my ability to be out and about.

So I am thinking about switching from Tecfidera. But I have no idea what I would like to switch to. I used to be compulsive about keeping up with the various medications. But there are so many now and I lost interest which was probably a good thing for my life.

Even though my MS has been very mild by the usual objective measures I prefer to be on a highly effective med. I don’t mind injections or infusions but interferons are out due to depression issues. I switched from Tysabri because I became JCV+ with a titre of 1.48 after almost 7 years and my disease was mild and inactive.

I am 61 yo and my other significant medical problem is asthma requiring Advair for decent control.

Can you point me in a direction to research? I do not find my current neurologist helpful beyond prescribing a DM med. He shows no understanding of my issues, priorities and goals especially controlling depression.

Sorry this is so long and thanks for your help.


Answer:
Excellent question

To summarize, you are a 61 year old relapsing MS patient with GERD, asthma and depression who's previous treatment included Avonex (worsening depression), Tysabri (low positive JCV index < 1.5) and Tecfidera (severe persistent GI side effects) and you would like another highly effective MS treatment.

Options are as follows (of FDA approved agents)

1. Gilenya (an SIP agonist and oral medication) is an option but should be used with caution (meaning pre-start specialty evaluation and good follow-up) because of age (potential cardiac arrhythmia issues) and asthma

2. Ocelizumab or Rituximab (both anti CD20 monoclonal antibodies) are options but require caution at 61 with potential breast cancer risk and less information on long term risks

3. Tysabri is my favored option, since you already know that this is well tolerated and effective based on your prior experience. We now know that administering tysabri with an extended dosing interval of 6 to 8 weeks dramatically lessens the risk of PML,  and in practice we have not seen a significant drop in efficacy with these dosing intervals. There is a planned clinical trial about to start that is designed to prove that extending the tysabri dosing interval does not lessen the effectiveness of this treatment. Depending on your location, you could consider participating in this trial for added safety and monitoring.

Good luck
Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
I have a question about brain MRIs. Why might there be white lines (look like parentheses) either side of ventricles on brain MRI? Thank you.

Answer:
Changes on a MRI in MS are most often considered to be demyelination, BUT there are exceptions. Patients can have other causes of a change on MRI. Also, some MRI pictures may be blurry or have artifacts on them that do not represent real change. It is important for a treating neurologist to review the films to help determine what any changes represent.

Benjamin M. Greenberg, MD, MHS
Vice Chair of Translational Research and Strategic Initiatives
Cain Denius Scholar of Mobility Disorders
Distinguished Teaching Professor
Department of Neurology and Neurotherapeutics
Department of Pediatrics
UT Southwestern Medical Center
Dallas, Texas

Here is My Question:
Lesion Location - Superior Frontal Gyrus

My last MRI showed foci of T2 and FLAIR hyperintensity found in the superior frontal gyrus. This was done on a 3T MRI. 
​
Does this mean they were in the cortex? I’m trying to understand exactly where that is, mostly for curiosities sake. 

Answer:
It is hard to say where the presumed T2 hyperintensity (what you refer to as a “lesion”) is located without reviewing the images. Radiologists are sometimes inexact in their descriptions. If the report says, “superior frontal gyrus” , this could mean the white matter, the gray matter (cortex) or both.

Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego