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
“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