Alemtuzumab autoimmune problems, this time it is a brain problem


As I said we will be back with more news of of alemtuzumab.

This time the person recieving alemtuzumab, developed a brain disease.  They have not found the causative antibody but the person responded to plasma exchange and was the third autoimmunity that the person had:-( 


  • This case describes the first reported case of autoimmune encephalitis as a secondary autoimmune complication of Alemtuzumab therapy.
  • Despite the absence of an identifiable antibody the patient responded well to immunotherapy including plasma exchange.


Secondary autoimmune disorders are a recognised complication of alemtuzumab treatment for multiple sclerosis. We report a case of autoimmune encephalitis manifesting as a polymorphic epilepsia partialis continua / status epilepticus seven months after the second course of alemtuzumab in a patient with previous autoimmune hypothyroidism and immune thrombocytopenic purpura. An MRI revealed multifocal cortical abnormalities and neuronal loss was evident on biopsy. Although testing for anti-neuronal antibodies was negative, the patient responded well to immunotherapy including plasma exchange. This is the first reported presentation of an autoimmune encephalopathy secondary to alemtuzumab therapy.

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  • Why is the blog, in particular MD, so against alemtuzumab? Do you have an axe to grind? I was treated with alemtuzumab and it has turned my life around. Please when you trash alemtuzumab you should balance your posts with the upside.

    • I will prepare a post on the upside of alemtuzumab over the next few days. The 8-year extension data was presented at ECTRIMS. Its impact on end-organ damage (brain volume loss and plasma neurofilament levels) and disease improvement are quite remarkable. And the drop-out rate of subjects makes the data stand-out.

    • Re: "How does Ocrelizumab compare with Alemtuzumab regarding end-organ damage and disease improvement?"

      Not quite as good; brain volume loss after year 2 on alemtuzumab is ~0.2%/year compared to ~0.35%/year with ocrelizumab. There are issues however with a direct comparison that I will need to discuss. HSCT is even better than alemtuzumab, with the caveat that there is more marked pseudoatrophy in year 1 with HSCT. Possibly because the chemotherapy used in HSCT is neurotoxic.

      It is a great pity Genzyme have put on hold their alemtuzumab PPMS study. It would have been interesting to compare outcomes in PPMS.

    • Although Ocrelizumab seems not to be quite as effective as Alemtuzumab regarding brain atrophy rates, would you say that Ocrelizumab is considerably safer of the two so perhaps a wiser choice for someone trying to decide which DMT to use?

    • A report about something that happened can't be described as 'trashing'

      Are you trying to say that such cases should not be mentioned on the blog?

    • Something profG mentioned that having alemtuzumab prevents access to ocrelizumab on NHS maybe profG can clarify os the vice versa is true i suspect not.

  • I couldn't agree more with anon 9:09. I'm 13 years out from my first round of alemtuzumab infusions and have had no relapses and stable edss + no sign of disease on annual MRI. This blog acknowledges that Alemtuzumab is up there with the best of dmds yet drips feeds every case where there has been a side effect / secondary immunity. My RRMS was considered very aggressive and Alemtuzumab halted it in its tracks – pity you never acknowledge these cases. Good post infusion monitoring is the best defence and my centre are excellent. Your drip feeding of Alemtuzumab bad news stories reminds me of project fear with BREXIT. Is it just an attempt to direct patients to cladribine? Has Team G delivered any real research this year i.e. research that directly improves the lives of people with MS? Too much time spent dissing DMDs and producing fancy brochures. If team G was a pupil my school report was "must try harder next year".

    • Glad alemtuzumab has worked out so well for you. Any secondary autoimmunities developed subsequently?
      With the full facts regarding side-effects and efficacy for any DMT, you are better able to make your own informed treatment choices. Now please tell me what's so bad about that?

    • "Has Team G delivered any real research this year i.e. research that directly improves the lives of people with MS?"

      Watch this space (it'll be well worth it) 😉

    • MD2 – I'm not sure how a patient can make an informed choice. The neuro says to the newly diagnosed patient that "Alemtuzumab is very effective at inducing NEDA…, but there are lots of possible side effects including x, x, x, x, x, x of which some are potentially very dangerous". How would you as a newly diagnosed patient really make an informed decision? I'd prefer a steer from the neuro e.g. "I have 200 patients under my care and the most effective drug from my experience is XX, although there is a x% risk of side effects with this drug." In reality a patient will make a choice based on how lucky they perceive themselves to be (how lucky they think they are to avoid the side effects). I don't believe Alemtuzumab have any side effects which are as frequent / awful as PML with Nataluzimab.

      On your second point, I've been following this blog for 9 years and still await some output from Team G which improves the lives of MSers. The spasticity trial results was a real downer for me this year. I look forward to some positive news / results.

    • A downer for you, think how I feel:-(

      As to your other Item…..try Giovannoni et al. N Eng J Med 2010;362(5):416-26 for example

      Alemtuzumab got the most liberal licence of a DMT thanks to the involvement of ProfG is another example

    • A big downer for me too. Never mind, onward and upward.
      As to the last point
      "Over half the patients we treat with alemtuzumab at Barts-MS are out of area patients coming for second opinions. Why? Because their local neurologist has not offered them alemtuzumab, or is not prepared to take on the monitoring burden and to deal with the adverse events when they occur. This is unacceptable."
      You're welcome.

  • Thankyou MD for highlighting yet another problem following treatment with Alemtuzumab. Everyone needs to be informed about the very real risks associated with this potent DMT to weigh up the pros and cons. I sincerely hope Cladribine proves to be an equally effective treatment because the side effects appear to be far less harsh. Wishing you and all your colleagues at Barts a very peaceful Christmas and New Year.

    • Unfortunately, cladribine does not do nearly as well as alemtuzumab when it comes to preventing end-organ damage. It is effect on brain atrophy puts it in the mid efficacy zone. However, this is the average response and does not necessarily apply to individuals.

      I still think we are underdosing on the cladribine front, which was deliberate to reduce adverse events. If only we could target higher doses to B-cells. We have some ideas about this that we need to explore.

    • ProfG I thought the high dose of cladribine was essentially the same as the low dose of cladribine and aren't the NEDA effects similar?

      MD has mentioned the differences in the trial populations. What is the effect on brain atrophy of dosing cladribine 2 years (CARE-MS) after onsets. What is the data from the ORACLE study? Does that show poor effects on atrophy too?

      Alternatively what is the effect of dosing alemtuzumab 9 years (CLARITY) after onset and does the atrophy rates look as good?

    • I don't think we've seen the best data for cladribine in terms of atrophy, and we also know that global brain atrophy is a pretty inaccurate measure. Let's hope #ChariotMS gets the nod from NIHR and we can badge some MRI work onto it with a focus on grey matter, which is more dependable.

    • I have a chat with ProfG about this and he still thinks there is an argument to be made about the T cells, gives me a cunning plan

  • Is it not remarkable that there has never been an alemtuzamab induced 'autoimmunity' that might be identified as 'multiple sclerosis', the classical 'autoimmune' disease of the CNS? Draw your own conclusions!

    • Re: "alemtuzamab induced 'autoimmunity' that might be identified as 'multiple sclerosis'"

      There have been cases diagnosed as NMO with anti-aquaporin antibodies. However, these could have been cases misdiagnosed as MS, when they had NMO all along.

    • there are at least 10 cases of alemtuzumab making MS MUCH worse. one case presented as a poster at ECTRIMS this year, several others published as case reports in journals over past two years.

      risk probably 1/2000

  • I understand that alemtuzumab fairs better with end-organ preservation than cladribine.

    where does natalizumab rank? closer to alemtuzumab or cladribine?

  • As someone who opted for alemtuzumab over cladribine a couple of months ago, recent news has been quite disheartening, as have the caveats about atrophy efficacy – which is what swung my decision in the first place. Appreciate the updates though. Faced with the prospect of losing brain, it's very difficult to go on theory about cladribine possibly being equally effective on atrophy as alemtuzumab if given earlier. Let's hope better data comes out in the future that helps people with what are very difficult decisions.

  • As someone who has also received Alemtuzumab I'd agree that it's not easy reading about newly identified secondary autoimmunities, but one case does not make for a sufficient rationale to reject any particular DMT. Obviously, knowing about all the pros and cons best facilities the making of an informed decision – so keep all the news coming MD.
    I'm 100% confident that this Blog has upset and depressed me on occasion, but I'm also 100% positive I wouldn't be anything like the informed and knowledgable and therefore proactive PwMS without it and the number of times I've had a 'that's great!' moment reading the posts far outweighs the downer moments!

  • If you have two courses of alemtuzumab your scans remain the same after 5 years but you see a deterioration in hand function is the deterioration due to residual damage and you should keep in mind the positives of therapeutic lag?
    Do you opt for another therapy and if so which one if not eligible for stem cell and if neither cladribine nor ocrelizumab are as effective?
    With little definitive guidelines for treatment dependent on how your MS presents what does an MSer do other than go with your treatment their consultant favours at that time

    Hope this question does get an answer because it feels as though people bounce from treatment to treatment

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