Is Ocrelizumab getting rid of EBV

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You have had NDGs take on this paper earlier and as I had done a post befiore I realised she had done the same thing, you may as well have it as an alternative view

Zivadinov R, Jakimovski D, Ramanathan M, Benedict RH, Bergsland N, Dwyer MG, Weinstock-Guttman B.Effect of ocrelizumab on leptomeningeal inflammation and humoral response to Epstein-Barr virus in multiple sclerosis. A pilot study .Mult Scler Relat Disord. 2022 ;67:104094. doi: 10.1016/j.msard.2022.104094.

Background: Ocrelizumab is an effective treatment for relapsing and primary-progressive multiple sclerosis (MS). However, the effect of ocrelizumab on leptomeningeal (LM) inflammation is unknown.

Objective: To investigate whether ocrelizumab reduces LM inflammation by reducing the exposure to Epstein-Barr virus (EBV)-infected B cells in relapsing-remitting (RR) MS.

Methods: This was a Phase IV, prospective, open-label, single-center, observational, longitudinal pilot study of RRMS patients who started treatment with ocrelizumab (NCT03025269). Clinical, MRI and EBV-antibodies outcomes at baseline, 12- and 24-month of the study were evaluated. The MRI outcomes included T2, T1 and T1-contrast enhancing (CE) lesion counts and volumes, LM CE count, and percentage brain volume changes.

Results: 27 RRMS patients started ocrelizumab and 24 remained on the treatment for whole duration of the study. Most patients remained stable (74.1%) or improved (18.5%) in their disability status. At baseline, 42.3% of patients showed LM CE lesions. The majority of patients remained stable in their LM CE status over the follow-up (72.7%). A significant decrease in percentage volume loss of cortex (p=0.009), GM (p=0.01) and thalamus (p=0.038) was detected, while T1-LV increased (p=0.02). A significant decrease of EBNA-1 IgG (p=0.013) was evidenced. An infusion-related allergic reaction led to discontinuation of the medication in one patient at first dose.

Conclusions: Treatment with ocrelizumab was safe and clinically effective. Brain volume loss and accumulation of T1-LV occurred. While ocrelizumab decreased humoral response to EBV possibly by reducing B cells, it did not reduce LM inflammation.

Is this the real MS being hit?….Give orcrelizumab and it reduces B cellls and antibodies to EBNA-1 decrease and brain volume loss decreases……..QED job done hurray!

Sounds like ocrelizumab is hitting the real MS. …..SID wrong as the DMTs aren’t a waste of time. However, inflammation in the brain surface (detected using MRI) was not reduced…Boooh. Is that because it is not the real MS….?

If we look in the blood antibody levels don’t drop following ocrelizumab, well I should say IgG levels don’t drop and oligoclonal bands persist on anti-CD20 treatment. IgM levels drop alot within 2 years and alot within a few months. So what what is special about cells producing antibodies to EBV. What happens to antibody levels to JC virus, CMV virus do they drop and we are being fooled by looking at total antibody levels, which perhaps are largely filled with what ever is infecting us (e.g. anti-SARS-COV-2 antibodies) at the moment. However, it is even more selective as “over the 24-month of ocrelizumab treatment, there was a significant decrease of EBNA-1 IgG (p=0.013) but not VCA IgG (p=0.993 = not close to being different). So if it was a case of killing cells that keep antibody responses going why didn’t VCA levels drop too.

EBNA-1 impairing antigen processing and MHC class I-restricted antigen presentation. This thereby inhibits the CD8-restricted cytotoxic T cell response against virus-infected cells. EBNA1 is expressed during all latency programs. Viral capsid antigne (VCA) is a more of a marker of past active infection, but what is the biology of this?. Killing B cells with latent infections?

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We know that ocrelizumab depletes the cells that would be latently infected with EBV and these should express EBNA-1 so is it removing the drivers for the production of antibody. A simple experiment for someone with repeatedly taken bloods to repeat the essential information to whether anti-ocrelizumab gets rid of EBV-specific antibodies, after all, these authours did collaborate with the Bard to give us you know what:-(.

Anyway I have long argued that the effect of ocrelizumab should out last, its dosing schedule and so should be more alemtuzumab and cladribine like and give long-term protection via short pulsed treatments…is targeting EBV-infected B cells. An attractive hypothesis….But hey that’s not new.

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Disclaimer. These are the views of the author and no-one else.

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MouseDoctor

16 comments

  • I had a long discussion with a senior neuro about treatment path going forward (PPMS on ocrelizumab).
    He said they are switching a lot of patients onto extended (9 to 12 months, possibly a lot longer in the future) interval dosis after the first 4 courses now seeing that most patients don’t recreate b cells in those time frames.

    So the pulse idea may already be out there.

  • I’m sorry MD, but I prefer NDG’s post – very well written. If I had to spend a year on a desert island with one of you, NDG wins. No ponytail, no Whitesnake or Black Sabbath blaring out from a 1980s ghetto blaster, no 48” Brutus Gold jeans, no smell of Bishops Finger real ale. Underneath you’re probably a nice northern guy, but NDG represents everything good in MS doctoring and research. Using Tina Turner’s words she’s simply the best.

    • Here we go again I’m all alone:-(..Im the bad guy has MS research.:-(…Happy to know that NGD is simply the best, but not sure we need to know your desert island fantasies…Brutus gold now I don’t remember them and in sure we don’t want to be smelling Bishops fingers

    • Just checked out Brutus Gold, stretch jeans from 1966 and 1970s maybe you are a bit older than me, at a 29 inch waist in the 1980s I was a levi person but wore my girlfriends pink Lyra stretch pants once…Now there’s a thought

    • SID, I didn’t know that this is a beauty contest on who can stay with you on a desert island. Personally, I would take the person with the best survival skills and not based on my own perceived notion of their MS expertise. Who ever is stronger and younger if the two will probably win.
      Fyi, the theory about anti CD20 affect being long term even without frequent dosing is nothing new. Even Dr. Hauser and others that were involved in the OCR studies voices this possibility.
      Again, did the scientific community cure MS? Not even close, but we have gotten closer to it and at present we have effective treatments to slow down progression. We are far from white, but not all is black… Especially for RRMS folks.

  • Not sure i understand the outcome here…..as an ocrevus user, is this good or bad news is ultimately what we want to know. Is this answer a bit of both?

      • Dr. Mouse, can you please restate the reasons why this is good news. I see one positive finding, do you see more?

      • Also, can you touch on the decrease in BVL? From former reading on this blog when Dr. g was still active, I remember him mentioning that there was very minimal affect on BVL reduction using OCR. Am I remembering it correctly?

        • Yes you remember properly but I think this is artifact. The same idea for cladribine based on the CLARITY trial data but the ORACLE data suggests it is time dependent.

          • CLARITY started cladribine 9 years after diagnosis
            ORACLE started at clinically isolated syndrome before MS properly diagnoses so difference is 9 years.

            Alemtuzumab studies started 2-4 years after diagnosis (CARE-MS I & II)

            Ocrelizumab trial data tarted after 6 yeaars

          • not sure it was ignored, the atrophy data was buried in supplementary data and presented in a way that it wasn’t obvious

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