Ocrelizumab removing infection protection in a small number of people

O

Alba Suárez EM, Tallón Barranco A, Puertas Muñoz I, Chamorro Hernández B, Robles Marhuenda Á. Non-late-onset neutropaenia following treatment of multiple sclerosis with ocrelizumab. Neurologia. 2021 13:S0213-4853(21)00026-8. Late-onset neutropaenia (loss of neutrophils which are our first line against infection) is defined as an absolute neutrophil count of <1.5×103cells/μL starting>4 weeks after the last dose of rituximab, in the absence of other identifiable causes. Late-onset neutropaenia is a rare adverse reaction to rituximab (observed in approximately 5% of patients). Rheumatic diseases constitute the main indication for rituximab; in these patients, neutropaenia appears after a mean of greater than 28 days. Ocrelizumab is another monoclonal antibody that binds to CD20 (a glycosylated phosphoprotein mainly expressed on the membranes of B-lymphocytes); in January 2018, it was approved for the treatment of relapsing-remitting and primary progressive multiple sclerosis. We present a case of neutropaenia following intravenous infusion of ocrelizumab in a patient with primary progressive multiple sclerosis who presented with neutropaenic fever, herpetic stomatitis ( is a viral infection of the mouth that causes sores and ulcers), and ecthyma gangrenosum  (a type of skin lesion characterized by vesicles or blisters which rapidly evolve into pustules and necrotic ulcers with undermined tender erythematous border. “Ecthyma” means a pus forming infection of the skin with an ulcer, “gangrenosum” refers to the accompanying gangrene or necrosis), only 20 days after infusion.

Many MS drugs can have an impact on neutrophils but this is unusual. Why does it happen as one guesses neutrophils do not express CD20. However, they may be triggered buy the B cell killing mechanisms. I am guessing these will get checked as part of you standard blood tests. It further shows that you immune system is there to get rid of infections removing large chunks of it with drugs can have consequences and a reason why you dont want to do it forever.

Marked neutropenia: Significant but rare in people with multiple sclerosis after alemtuzumab treatment. Baker D, Giovannoni G, Schmierer K.Mult Scler Relat Disord. 2017 Nov;18:181-183. 

Neutropenia has been reported with cladribine when used within the cancer setting and is one of the major problems with HSCT, which is associated with loss of neutrophils and severe and sometimes fatal infection risk .

COI Multiple

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

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MouseDoctor

9 comments

  • So I stopped treatment with Ocrevus (O) earlier on when the pandemic was winding up. I had started it after 25 years of Interferon 1-B injections. Things weren’t getting worse, it just seemed like a good idea since O worked on Primary progressive, and I was getting older (61). Stopping the every two day injections was really quite liberating. But now in hindsight, I am interested in following the whole O + Covid + ? thing, as I am interested in what I am avoiding, and what I am missing, as well as, how others are reacting including Roche. So this info gets put in under the heading of another question mark, and I wonder how many question marks one can handle. The ethical thing, in my opinion, is that O patients should be supported in having a plan B. But that’s why they went on O, specifically to not have a plan B. Certainly, there is little for me and I (for now) have to hope that my Betaseron treatment for 25 years gave me enough edge to survive another 20 years without substantial downturn. It feels precarious, but so too would have been me continuing O, in my opinion. Cancer and now infection risks? Too much. But I am surprised here, by no comments thus far. I have found in reviewing facebook posts, an expected tendency to overlook the downside and even discuss hopes that have been proven false. So at this point, I suppose I am advocating a plan B, and wonder what that would look like, for me and others maybe no longer too enthusiastic about their O?

    • Current plan B: skip O infusion due this month. Get tested for CD19+ in Sept. Get vaccinated when B cells return. Switch to Cladribine.

        • I think has something to do with Prof G’s extensive coverage on his concerns (opinions) over CD20 treatments, and pwMS visiting this site somehow built a biased understanding of risk/benefit of CD20, Cladribine and Alemtuzumab.

          • Both of those put you in about the same boat as O, don’t they? I’m not sure which direction of opinion you are referring to. I know the moderator of one MS site thinks this blog changes opinion too much, so she doesn’t like references to it. Commenters there, many of them, are just oblivious to the reality of depleting B cells and have never thought about “what if…” They are expecting an antibody response one way or the other, and some are making up their own criteria for having one. My understanding of the risk/benefit is, no harm if you are young and healthy, otherwise be careful and you run at your own peril. I would not want to hear that if I was just starting O.

          • Prof G argues the risks associated with the two IRTs are front-loaded, but from what I can understand they are not only front-loaded but also with long-term consequences. Whereas O, usage up to how long the IRTs provides remission in average, are very safe.

            Plus the efficacy from the two IRTs could be nothing more than B-cell suppression (at least in the case of Clad?), there is not enough evidence so far to convince me (just an average Joe, not a doctor but I believe I can read with a relatively unbiased set of mind).

            Do we all need Alemtuzumab and if Alemtuzumab is not followed up with other treatments does it really offer better long term outcome than O? I don’t know but I would think it would be No to both questions.

      • If you were 63, and had avoided thus far, moderate disability, would you still persist with such a strong medication with known issues, or leave “well enough”, alone? Just curious.

  • Hello again MouseDoctor- Referring to your response above, I think it’s more than mud, for me. 30 with the health and vigor of youth (despite MS)?, I might go for it again. There are other issues- I live in ground zero for defiance against science. A “true man” isn’t “covid concerned” where I am, and they don’t want microchips implanted with a vaccine. It’s all more than “hesitancy”. \Those attitudes will not change and it is doubtful if we will ever reach and maintain 70% vaxxed. In my area I think we are below 50%. The pandemic is endemic, face it. My blood sugar is a couple points over normal, under control. A slight heart issue under control. Slight hypertension under control, Cysts in my kidneys. Abnormal bladder shows in bloodwork with an enlarged prostrate but no real indication of cancer, yet. All common relatively manageable stuff for 63, but stuff that you don’t want with covid. I engage with the local deniers shoulder to shoulder regularly in the context of doing something that keeps me happy and vigorous. So I want vaccine response with no issues. I don’t want life with avoidance and potential reluctance. I write this all because I want to paint a picture of reality for some, that others may not realize (I don’t think).

    • Not a doctor, but personally I would probably not go on anti cd20 in that case.

      Covid seems like big enough risk to optimize vaccine readiness of the DMT in your case.

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