Monday, 14 August 2017

#NeuroSpeak: what do when you have failed a IRT?

Sequencing of DMTs will become increasingly complex. #NeuroSpeak

Somebody asked over the weekend what I would do if someone failed alemtuzumab and had a persistent lymphopaenia. In short it depends on individual factors. 



I have had three patients like this already.

#1: One patient had 5 courses of alemtuzumab and had developed anti-alemtuzumab antibodies and had very little depletion after her last round of treatment. Her disease remained active on MRI (multiple enhancing lesions). Her lymphocyte counts were around 0.9. I recommended rituximab, but as she was hoping to start a family she opted for de-escalation therapy and chose glatiramer acetate. Her neurologist tells me she is doing well on GA. This case illustrates that you don't always have to go upwards in terms of efficacy, you can de-escalate and use a platform therapy after an IRT (immune reconstitution therapy).

#2: The second case failed alemtuzumab therapy at month 17 into her two years of treatment. Interestingly she repopulated rapidly after her second course, i.e. her lymphocyte counts were 0.8 at month 1 and were 0.9 the week before she started her second course of alemtuzumab. I suspect she may be another case of anti-alemtuzumab antibodies. She had previously failed glatiramer acetate. As she was JCV-seronegative she elected to be treated with natalizumab. This patient was offered HSCT, but turned it down when she realised there would be a good chance of her not being able to have children. The haematologist had given her 45-50% chance of going into the premature menopause. She had the option of egg banking, but as her MS active she was not prepared to wait 2 months and go through the relatively stressful, and invasive procedures, of ovarian stimulation and egg harvesting. Then there is the cost of storage.

#3: The third case who I saw last week with her second relapse after her second course of alemtuzumab (month 19). Interestingly, despite having just started natalizumab she still had a relapse. Her lymphocyte count was 0.8. when she started natalizumab. This last relapse came on just 2 weeks after her first infusion of natalizumab. This shows you that almost all DMTs take time to start working and that a relapse takes weeks to evolve. In other words, if you are destined to have a relapse in the next week or two natalizumab will not prevent it from occurring. This patient was also offered daclizumab, but after the recent death due to fulminant hepatotoxicity on daclizumab, she decided to go with natalizumab. Interestingly, this patient has also just developed Graves disease (thyrotoxicosis) so she was hit with a secondary autoimmune complication of alemtuzumab without deriving the long-term benefit of its efficacy. This particular patient would have chosen ocrelizumab, over natalizumab, if it was available. The option of rituximab is not on the table as in the first case as NHS England have stopped us using rituximab to treat MS.

I am hoping to create a ClinicSpeak App that deals with all the issues raised about the sequencing of treatments. The purpose of the App is to help people understand issues such as the ones raised in these case vignettes.


CoI:multiple

9 comments:

  1. Replies
    1. Exactly what I was thinking.

      Delete
    2. Extremely well. She has noticed an improvement in her walking distance and bladder function. I haven't seen her for over 6 months so I assume she remains relapse free; in our centre no news is usually good news.

      Delete
  2. > she was hit with a secondary autoimmune complication of alemtuzumab without deriving the long-term benefit of its efficacy.

    I don't think it's fair to say she has not/will not derive long-term benefit from alemtuzumab. Even if it has not totally stopped new inflammation it has probably toned down her disease course a fair few notches.

    ReplyDelete
  3. I read With great interest how tricky and patient-dependent is treating MS , and the mixed blessing to count with so many drugs. In Uruguay we hardly have such discussions, (irónic here) as we just count with interferons and glatiramer . And quite recently, with fingolimod. MS treatment is managed by a Gov't office. It is very frustrating!

    ReplyDelete
  4. "One patient had 5 courses of alemtuzumab"

    I thing 3 courses where the maximum

    According to you there is a 80% chance to develop antibody against the drug

    "ProfG's post this morning me reminded me of something a neurologist told me yesterday about their experience with multiple cycles of alemtuzumab, where they felt the treatment stopped working."

    Nearly 80% of people treated with alemtuzumab make "inhibitory antibodies".


    So why you gave 5 courses?

    ReplyDelete
    Replies
    1. Yes this is one of our patients who has taught us about NABs to alemtuzumab. At the moment NHS England are only allowing 2 course of alemtuzumab. We are waiting for clearance to give a third course.

      Delete
    2. Thanks Dr. Giovannoni for reply

      Hope she´s doing ok

      Luis

      Delete
  5. Congrats to Dr:Baker and colleagues they apear in the new issue of Jama

    Neurology

    http://jamanetwork.com/journals/jamaneurology/article-abstract/2630677?utm_medium=alert&utm_source=JAMA+NeurolLatestIssue&utm_campaign=14-08-2017

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.