Rapid memory B cell increase associated with alemtzumab failure, but where does the ABN stand on MS treatments currently.

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We already know that after alemtzumab treatment there is a rapid rise in immature B cells, but in general memory B cells stay low for the first couple of years after treatment onset. However not in this case, there was a notable increase in memory B cell numbers and this person appeared to fail alemtuzumab. Is this cause and effect or just a chance finding, after all levels of lymphocytes in the blood are generally not associated with relapse. However, let more data that does not argue against the memory B cell hypothesis…which has been going strong for 3 years.

The person was switched to ocrelizumab. This week profG talked about someone worried about alemtuzumab in the COVID era andthey decided to switch to ocrelizumab. I then asked why not to cladribine as it could have merits as I have discussed (COI multiple) and he said the label made that difficult and then wondered whether you could get a change in NHS England policy, they changed the dosing for natalizumab, to allow presciption.

I wondered what the current ABN guidelines are as I thought the Association of British Neurologists have changed their guidelines. However, I went on their website today but saw the one you can find is back to March 11 2020 and there is a firewall placed for health care professionals. However, I am not dreaming, becuase I went through my history and have the document.

ABN GUIDANCE ON THE USE OF DISEASE-MODIFYING THERAPIES IN MULTIPLE SCLEROSIS IN RESPONSE TO THE COVID 19 PANDEMIC
DATE: 18 TH May 2020
AUTHORS: Alasdair Coles and the MS Advisory Group
SCOPE: This guidance applies to the recovery phase of the COVID 19 pandemic and any future resurgence. We appreciate the risk of becoming infected with SARS-CoV2 will varyover time and between regions.
DATE OF REVIEW: 01 November 2020

However afer a hunt I found these

https://cdn.ymaws.com/www.theabn.org/resource/collection/65C334C7-30FA-45DB-93AA-74B3A3A20293/ABN_Guidance_on_DMTs_for_MS_and_COVID_19_VERSION_18_May_FINAL.pdf

11. Cladribine should be started cautiously on a case-by-case basis when the risk of SARS-CoV2 is very high. Re-treatment should be delayed until the risk of infection is level 3 or below.

12.Alemtuzumab should only be started, or retreated, when the risk of SARS-CoV2 is low [threat level 1 or 2], except on a case by case basis.

Now that ProfGs name is not on the document, although no doubt he will be pars of the MS advisory group maybe he can give his opinion on them or discuss them in relation to his current table of choices. Maybe they have been ripped up, after all the last ones did not appear to be based on science reality at the time and the MS Society still had the April update. Maybe ProfG does not want to acccused of being a flip-flopper again (name on guidelines one day/Different ProfG views the next day:-) May be he can answer why the next date of review will be in Novemebr, when there is so much data that will surface before then.

Highly active RRMS and ocrelizumab after failure of alemtuzumab therapy.Vališ M, Ryška P, Halúsková S, Klímová B, Pavelek Z.BMC Neurol. 2020 May 21;20(1):202. doi: 10.1186/s12883-020-01789-y.

Background: A high multiple sclerosis activity while on alemtuzumab is rather uncommon compared to moderate-efficacy drugs. The purpose of this case report is to present a case of a 37-year-old female patient with bronchial asthma and no other medical history, whose disease activity required switching from dimethyl fumarate to fingolimod, then to alemtuzumab and finally to ocrelizumab.

Case presentation: In our patient, two severe attacks were observed and treated after administration of the first pulse of alemtuzumab. After six months of therapy, patient’s immunological profile showed the expected decrease in CD4+ and CD8+ T-cells and, markedly increased values of CD19+ B-cells. Surprisingly memory B-cells, which typically repopulate very slowly following alemtuzumab treatment, were above baseline levels. Regular administration of ocrelizumab based on a standardised scheme, after the alemtuzumab therapy failure, resulted in the stabilisation of the patient’s condition both clinically and radiologically.

Conclusion: Thus, when the alemtuzumab treatment is unsuccessful, the authors recommend testing T- and B-cell levels and proceeding with an early switch to ocrelizumab if high B-cell counts are found.

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MouseDoctor

6 comments

  • Thanks for this. What’s the current thinking on ocrelizumab? I’m waiting for my delayed 2nd full dose to get the green light

  • Thanks – found it. Still a tad vague though about continuing ocrelizumab. What about shielding being reviewed?

  • Is there any evidence demonstrating normalisation of thyroid function in patients that switch from alemtuzumab to ocrelizumab after developing Graves’ disease (e.g. supporting your hypothesis that secondary autoimmunity is driven by B cell rebound above baseline)?

    I’ve found a few papers showing rituximsb (vitamin R) has been used to good affect in small doses but I don’t know how strong the evidence base is.

    Secondly, if the evidence base exists, how would one go about convincing a neurologist to take the risk?

    Hoping everyone in the UK is surviving the lockdown and staying safe. God knows the economic fall-out this is going to cause (10% unemployment in Australia already). Stay strong people and take care of each other.

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