Q&A 81: Low JCV-index positive: should I switch to an anti-CD20 therapy or not?

Have any of you pwMS on natalizumab have similar concerns? How many of you have a low JCV index positive and have decided to stay on natalizumab?

Case

I was diagnosed with MS in Feb 2015 at the age of 42. I took glatiramer acetate (Copaxone) for more than 4 years until I had a bad relapse with very high MRI activity (incl. black holes) in Nov 2019.

Upon recommendation of my Neurologist, I then switched to Natalizumab (Tysabri) in Feb 2020, first did infusions and subsequently continued with the teh subcutaneous injections.

I tested JCV positive before starting natalizumab, but my index has always been very low, ranking between 0.22 and 0.33. Last year, it was always just above 0.2.

I have now been on natalizumab for a total of 5 years, about the first three years on 4-week intervals and then extended to 6-weekly intervals.

I have had no MRI activity, no new lesions and no measurable disability progression since changing to natalizumab. I still work full time, have no physical symptoms, regularly do sports, and I only struggle with fatigue, cognitive issues, Utthoff, etc. Overall I am pleased with natalizumab, despite the often rather nasty crap gaps that I get on the 6-week intervals. My JCV index is checked every three months, my MRI is checked every 6-12 months, and my blood is checked every 6 months.

So far, my Neurologist still seemed ok to keep me on natalizumab despite being JCV positive. At the end of last year, however, I started to get extremely anxious and concerned about increasing PML risk myself.

I discussed therapy change with my Neurologist. He suggested switching to either ocrelizumab (Ocrevus) or ofatumumab (Kesimpta). Necessary blood tests are due in a few days, and despite having discussed it all twice with my Neurologist, I am still feeling uncertain about giving up "magic" natalizumab, which enabled me almost to forget my MS. I am also worried about the immunosuppressive effects of Kesimpta/Ocrevus and getting reoccurring infections. At the same time, I tell myself that this is a rather stupid concern when the option is the risk of PML. My Neurologist would prefer me to switch asap but is not (yet) insisting or pushing.

I want to ask how you would assess the potential PML risk based on the details I shared. I am simply worried that I might never be as well again as I am under natalizumab, but I do not want to play "Russian Roulette" with PML either.

Thanks

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Answers

There is no right or wrong answer, …..