First case of PML on ocrelizumab after 2years treatment in a 78 year old.

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This newsflash is an appropriate one at the moment asthe World has gone mad and COVID-19 vaccine hysteria is travelling faster than the virus itself. An adverse event that co-incided with vaccination has got national governments ignoring their own regulators and reducing “vaccine confidence”. Vaccine hesitancy as a consquence of such hysteria is likely to cause more damage than it is seeking to avoid. Is the adverse event causally related? or a chance event? It looks like the adverse events occurs with the other vaccines also and at a rate that is no higher than the chance of the event occuring as part of daily life and death. This is like feeding Sweeties to the anti-VAXXers.

So what makes the SH1 stick?

Cladribine was tarred with the side-effect brush in 2010/11 when that occuring in the cladribine trials was no worse than those in the ocrelizumab trials in 2017. Today in the press ocrelizumab gets tarred with the PML brush, but should we have a worldwide boycott of ocrelizumab? No because it doesn’t make sense to do such a thing. Ocrelizumab is beneficial in controlling disease.

Obviously is a risk we should be aware of but one has to say we have known about this risk for a long time as PML was seen with rituximab in some individuals. As you age, your immune system ages and stops working as well as it used to do. This is perhaps why older have worse issues people with COVID-19. Likewise, it is known that long-term continual depletion of B cells increase the risk of severe infection, this why ADIOS is such a sensible study to do where you assess the question: Do you have to dose all the time for ever? Am sure if you checked the delay in the infusion of ocrelizumab during the pandemic was well tolerated and disease control was effective

However, as for this being news…It is not news.

ProfG reported this case two years ago of someone from America who was given ocrelizumab at the age of 76

https://multiple-sclerosis-research.org/2019/10/de-novo-pml-on-ocrelizumab/

“Even ‘normal’ elderly people have a very small risk of getting PML, it comes as no surprise that age is an emerging PML risk factor in MS, and explains why relatively safe DMTs have been associated with rare cases of PML”. 

Being older means they are more likely to have comorbidities, immunosenescence and less biological reserve to deal with serious and life-threatening infections. 

Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy Patel A et al. JAMA Neurol. Published online March 16, 2021. doi:10.1001/jamaneurol.2021.0627

IMPORTANCE Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus that has no proven effective treatment. (Should have gone to Spec Savers…..Then they may have seen the study by NDG…seemed effective to me) Although rare cases of PML have occurred with other anti-CD20 therapies, there had been no prior cases associated with ocrelizumab.
OBJECTIVE To report the first ever case of PML occurring with ocrelizumab monotherapyin a patient with progressive multiple sclerosis without prior immunomodulation.
DESIGN, SETTING, AND PARTICIPANT This case was reported from an academic medical center. The patient had multiple sclerosis while receiving ocrelizumab monotherapy.

EXPOSURES Ocrelizumab monotherapy.
RESULTS A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient’s symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab (check point inhibitor. NDG used additional cytokines) treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy.
CONCLUSIONS AND RELEVANCE In this case report, PML occurrence was likely a result of the
immunomodulatory function of ocrelizumab as well as age-related immunosenescence.
This case report emphasizes the importance of a thorough discussion of the risks and
benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly
patients.

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MouseDoctor

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  • Ah I’m supposed to move from Natalizumab to ocrelizumab because of JC+. Should I reconsider or is the risk negligent on Ocrelizumab compared to Natalizumab?

  • Talking of vaccine confidence…

    Is it correct the the one currently being vilified in Europe (Oxford Astra-Zenica) is a third of the price of the Pfizer one?

    Are countries still buying the Pfizer one and are they anoyed their competitior’s vaccine is considerably cheaper (and easier to store?)

    I wonder who is stirring the pot?

    • I think it is about 7th of the price about $4 verses $30.

      Countires have already bought the option…I think this is vaccine nationalismat the root of the problem

    • There;s some crazy, hysterical anti-science overreaction in Europe and I suspect that envy on the UKs success in vaccinating our population is part of the reason.

  • Please consider changing the title of this post as it creates a level of anxiety that is not valid once you know that the patient was progressive and 78 years old.

    • Thank you for suggesting this – my first reaction was like “another one?” then realize it is the same case you would ask why the physician prescribed OCR in the first place.

  • The comorbidity of age is inevitable depending only on the date of your birth. Other comorbidities are to an extent a matter of choice. If you think it advisable not to treat because of age, why do not consider other factors in determining treatment decisions?

  • Hi MD

    As I’m coming up to my 4th full dose of Ocrelizumab & I have to say it has been a difficult few years, dealing with numerous infections & MS I fear, progression – how would a patient know what to look out for especially if you’re having lots of problems anyhow. I had my post infusion bloods 3 wks ago – & what would you recommend a patient look out for from these results to know type of symptoms a low lymphocyte count will give you generally? As someone who has just gone through an age thing & I don’t want to mention it as it has caused me some grief & I’m not too good at hearing, that in most people it doesn’t affect them too much 🙁 – but to be managed through to my old age – what are the options for patients over 50 for MS treatments. Should the dosing be administered differently as our immune system is already starting to weaken with age & could some of the monitoring be more robust – to enable this poor patient’s symptoms be picked up sooner & lastly, if there’s an anti-dote that can off-set the onset of PML – Or if not, is this something that can be looked into and patients can have this information on the day they make their decision to go ahead with the therapy. It could help support someone’s decision about going ahead – as with this therapy if things start to go south, they fill there are options if PML is a risk.

    I hope you’re all keeping well & the Covid nightmare is starting to show signs of slowing down.

    All the best,
    Jane

    • “I had my post infusion bloods 3 wks ago – & what would you recommend a patient look out for from these results to know type of symptoms a low lymphocyte count will give you generally?”
      I would look to see that my B cells are still depleting, but after the third dose they wont be there anyway. I am afraid there is nothing in your blood that is going to say this is where you will be. As for over 50 I think on ProfKs study there is no upper limit.

      Should the dosing be done differently. I have been arguing for some years that ocrelizumab is probably is an IRT meaning long term benefit from a short term treatment, after three cycles there appeared to be no more activity of 18 months of nothing as 3 more doses. However there was some activity but these people were younger. The company should do the study, but they wont so adademics will do it but it will take time. I am sure we will see that dosing does not have to be done so often. I suspect we should be looking to Sweden for insight they have a significant cohort of people on rituximab I am sure they do not treat for ever.

      Is there an antidote for PML….partly in this case they tried to use one and it didn’t work but NDG recently reported a case where she cured people from the PML-causing JC virus.

      Remember ocrelizumab is a best seller and there are thousands and thousands of people taking the drug and therefore the risks of PML are very, very, very low

      Thanks for your kind words as for keeping well, I am sure we have all had our COVID moments, but sadly I think our COVID nightmare is only just beginning and we will see the fall-out of this over the next year or more. This has been happening already:-(

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