Disease reactivation after cessation of natalizumab and switching to fingolimod

Rinaldi et al. Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler. 2012;18:1640-3.

Background: Clinical and/or neuroimaging evidence of disease reactivation has been described in MSers  after a break from natalizumab. 

Objective: To evaluate fingolimod as therapeutic option following natalizumab. 

Methods: Twenty-two relapsing remitting MSers having JC virus antibodies (JCVAb+) in serum were switched from natalizumab to fingolimod after a three-month washout period. Neurological evaluation with the Expanded Disability Status Scale (EDSS) was performed monthly for a mean follow-up period of nine months. 

Results: In 20/22 MSers, MRI was obtained within one month after therapy initiation. Disease reactivation was observed in 11/22 (50%) MSers: clinical relapses in six MSers (four MSers within the first month of therapy) and MRI activity in a further five MSers (three MSers within the first month of therapy). Clinical and/or MRI signs suggestive of disease rebound were observed in three MSers. 

Conclusions: Our data indicate that fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from natalizumab.

Rigau et al. Lethal multiple sclerosis relapse after natalizumab withdrawal. Neurology. 2012 Oct 24. [Epub ahead of print]

Jander et al. Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. Mult Scler. 2012;18:1650-2. doi: 10.1177/1352458512463768. 
“These studies and case reports confirm mine and many other neurologists’ observations of rebound on natalizumab withdrawal. Most of us feel that this rebound is in excess of what activity MSers had before they started natalizumab. How to prevent it? It is difficult, because you want to make sure that JCV+ MSers who are switching from natalizumab (Tysabri) to fingolimod (Gilenya) are not in the pre-symptomatic phase of PML, which is why we advocate a 3 month washout period. The washout allows your own immune system to reconstitute the CNS and find any rogue virus. The problem with this strategy is that it allows your MS to comeback with a vengeance. Some of us have started prescribing pulsed monthly steroids to cover this period, but this does not appear to prevent the rebound entirely. There are several trials testing different washout periods and switching options that will hopefully allow us to make more evidence-based recommendations shortly. At present I am too concerned about carry-over PML on fingolimod to recommend anything less than a 3 month washout. If we can increase the diagnostic confidence of excluding early asymptomatic PML I will obviously change my recommendation. Please stay tuned to this blog; we will come back to you with more posts as data becomes available.”

38 thoughts on “Disease reactivation after cessation of natalizumab and switching to fingolimod”

  1. Drugs never cure a disease.They merley hush the voice of natures protest and pull down the danger signals she erects along the pathway of transgression. Any poison taken into the system has to be reckoned with later on even though it palliates present symptoms. Pain may disappear,but the patient is left in a worse condition, though unconscious of it at the time. Daniel.H.Kress, M.D

    1. Not sure I agree with this; there are too many examples to the contrary. Try telling this to someone who has been given the green light from cancer after chemotherapy.

    1. Same as fingo, you need to make sure you are PML negative. Therefore a 3 month washout with an MRI and CSF analysis.

  2. "I am extremely disappointed. I send you out for exciting new designer drugs and you come back with tomato sauce."House., M.D.Sometimes Docs talk rubbish

    1. I always found that once you'd seen a few episodes of House you'd seen 'em all. Patient comes in with mysterious disease, doctors go up several blind alleys only for House to ride to the rescue in the last 5 minutes sort of thing.

    2. If you were paying for him it would cost you a packet as you have CT, MRI, lumbar puncture and brain biopsy every episode and that's if you have a ingrown toenail:-)PS I never met a Doc that watches it.

  3. At ECTRIMS 2012 have been published papers about the efficacy of fingolimod to prevent TYSABRI-rebound, other papers to the contrary, other papers that say steroids are effective, paper that say copaxone is effective, other papers say the rebound is inevitable. What is the actual percentage of patients with rebound when they leave tysabri? I've heard that there are specific phenotypes never develop PML, is this true? Thanks, Alvaro.

    1. Tysabri is recommended for RRMS not other subtypes, a trial on progressive MSers is ongoing. There is no reason to believe they are not at risk also

  4. All this goes to show just how risky current DMTs are. We're paying loads of money for toxins. Makes no sense. We need to do away with all DMTs until a repair option can be found that is worth investing in. NHS must stop funding pointless DMTs.

    1. You can't repair what has already been lost and you need DMTs to minimise this. Then you can think about repair strategies.

    2. If you have RRMS (like I do) and the relapse rate is cut from every 8 weeks to 1 every 3 years on average, then like me, you'd fight like mad to keep on that DMD.I'm not on Tysabri as my MS isn't active enough and I'm glad I'm not. You are stuck between a rock and a hard place with RPMS – if you don't take something that hits the MS hard, like Tysabri then you go downhill fast.I'm guessing anonymous that your MS isn't that bad and that you've never had to fight to get treatment. Aren't you lucky? Why are the CRAB drugs risky? I'm on beta-interferon 1a and my blood tests are fine. 12 years this year.

    3. I agree with MD2 a repair only strategy is the wrong strategy"You need to put out the fire before you can think about rebuilding the house other wise it is more to burn".MouseDoctor not M.D.

    1. No, they don't. But they stop it from destroying lives. So your point is what? Do you have a viable alternative to drugs?

    2. "NO Drugs never cure MS" so as a double negative does it mean that "drugs cure MS". We have to wait and see what happens with the new DMT

    3. MouseDoctor,It was only slips of the tongue as we all understand what was the message : "No drugs cure MS".what about your statement: "If you do not have JC virus then you should get PML"….is it so?I suggest to limit your comments to the message and not to tiny mistakes done here and there…

    1. Who wrote the article? A website selling space to the max for nutriceuticals. But read the content and it has endlessly been addressed here on the BLOG.

    1. We went there with this…piece last week or two weeks ago, you need to visit more and keep a pace with the readers comments/

    2. Who is Health Ranger? Someone who had borderline health problems and who ate a decent diet and decided to become a self-proclaimed 'expert' on disease. This guy isn't even a doctor. He isn't ill. He doesn't have MS and probably has no idea how complex MS. So what if he never eats beef, doesn't use detergents and seems to like being photographed next to rivers. He doesn't know anything about 'real' diseases. If Karma was just and true, he'd have MND or MS or a 'proper' serious, incurable, degenerative disease and learn some humility and empathy and respect.

  5. Oh for heaven's sake! Only someone who doesn't have active RRMS can think that. A relapse is a bit like having a sprained ligament or twisted ankle. It takes about 6 weeks to recover from a relapse. So, if you keep injuring the same bit over and over again, it won't heal. That's what the DMDs do – stop/slow the relapse rate and give the body a chance to recover from the damage done and regain some fitness. YOU try shuffling around, doubly incontinent, half blind and see how long you can put up with that quality of life. Someone offers you a chance to stop the relapses that are ruining your life and you'd say no? How stupid is that?

  6. I see you are still discussing the efficacy of drugs I would have asked you dear Mouse if you could provide us with a link where they were all currently available ms drugs with data on the efficacy like distability rate , side fx and so on . from this point of view it seems to me that only a tsyrabi have great impact on ms but dangerous side fx .

    1. This is Prog G's domain, he has all the info to hand and in his headTrials were done at different times the relapse rates from when thebeta interferon trials were done have fallen dramatically in the placebo arms.Interferons (rebif, avonex, betaseron)Down ~30% Injection reactionsflu like symptomsGlaterimer Down ~30% Injection reactionsAtrophy of Injections sitesAubagio (USA) Down ~30% Headache/Hair thinning/RunsBirth DefectsNataluzimab Down ~70-80% Dizziness/ReactionsPML-InfectionGilenya Down ~50-60% Heart Rate EffectsDizziness/Eye ProblemsInfection/Tumors probelem with immunosuppression

    2. simple logic – you are highly likely to deteriorate no matter what. Always go for the most powerful treatment if your risk profile can afford it.

  7. thnx for for fast response , as I assumed tsyrabi is most efficient 70 – 80 wow , but unfortunately among the most dangerous

  8. Lemtrada is as effective its use is not associated with PML..yet but about 30% of people get another autoimmune condition and there is infection/tumor risk. However it is not yet licensed

  9. MD, if you were JCV-ve, would you go for Natalizumab or Alemtuzumab (when accounting for all risk/benefit factors) ?

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