Should I Switch From Tysabri to Tecfidera?

Here is My Question:
My neurologist thinks I should consider changing MS therapies – from Tysabri to Tecfidera. In terms of MS therapies, I have been through Copaxone, an interferon ß (specifically Rebif) and am currently on Tysabri. I think most of the disability I now experience developed while I was on Rebif, so it did nothing for me. I have been on Tysabri for 4.5 years (5 years in Jan.). While my MRIs (always 3T every 6 months; now every 4 months) have been stable during this period, I am JC virus positive and my index values (only monitored every 6 months over the past year) have remained 1.0. I am told that given the numbers listed above, if I remain on Tysabri my chance of developing PML are roughly 1/140. Her experience with Tecfidera is that most patients initially experience some side effects (diarrhea, flushing) but in roughly 75% of cases, these go away with time. But, in 25% of the patients, the just don’t like how they respond to Tecfidera and go back on what they were on before, or in my case, Tysabri. I am a biomedical scientist and like the idea that we know fairly precisely how Tysabri works and have no real idea how Tecfidera works. I think I should remain on Tysabri for another year (with MRIs every 4 months and JC indexes every 6 months) and revisit this question when there might be more information and/or another option (e.g., daclizumab) rather than Tecfidera. What do you think? Any information greatly appreciated.


Answer:
If you look at the table that I published on a prior blog CLICK HERE, you will see the following probabilities for PML with different JCV antibody index values for patients on therapy for at least 49 to 72 months:

Index < 0.9 : risk 1 in 2500
Index < 1.1; risk 1 in 1429
Index < 1.3: risk 1 in 833
Index < 1.5: risk 1 in 769
Index > 1.5; risk 1 in 118

Given the wide fluctuation in risk of PML with relatively small changes in antibody index, I would be cautious in how you interpret these values. I basically lump everyone at or above an index of 1.0 in the same category until we have more data and longer follow-up. I am told that this table, which was based on 51 cases of PML, has been updated to reflect data on over 70 cases  and the probabilities change very little with this new data. I will update the website with this new data when I see it

I guess the points I would make are the following:

1. Your risk of PML may or may not be as high as quoted by your neurologist, but we all agree you do not fall into a no risk category; at a minimum you require continued monitoring. I would encourage antibody testing every 4 months and a brief 5 minute MRI (FLAIR and DWI only with no contrast) every 4 months to assess for pre-symptomatic PML, if you remain on Tysabri or for 6 months after stopping Tysabri (if this is your choice). After stopping Tysabri I encourage MRIs 3 and 6 months after the last dose.
2. There are side effects with Tecfidera but they are usually manageable; we know little about the exact mechanism of action of any DMT other than Tysabri.
3. We do not have good evidence that switching from Tysabri to Tecfidera (or other DMTs) prevents individuals from experiencing relapses in the first 6 months although the relapses may be less severe than if off all DMTs during this interval.
4. Patients have the right to make their own choices as long as they are reasonable. You certainly seem informed (more so now) and should be allowed to participate in this decision process.
   

I hope this helps

Rip Kinkel