PML found in MS patient taking Ocrevus

[SuzE-Q]

Suze-Q, you mean it is like a re-bound effect?

Yes, that's exactly what appears to happen. I haven't kept up with the stats on how often, or if there are ways to counteract it, or how many of the new treatments have this potential side effect upon stopping the treatment. Maybe someone else has that info.

But it's one of my concerns, it's like it puts the disease in 'abeyance' while on the treatment, but if you stop it, all progression that had been 'postponed' while on it comes rushing back full force. That's in addition to the risk of PML while on it. Try parsing all this out if you start developing symptoms while ON or just after stopping one of these!

Or, what if the treatment didn't seem to work, or the side effects were too great, or your JC titers become too high and you need to stop it soon after starting it...and you STILL have to contend with the potential of this fast inflammatory reaction and progression?

That scares me a lot.

Maybe someone else can let me know it's rare or there's ways to counteract it than quickly hopping on another mab (monoclonal antibody)?

Do ALL the mabs, and newer treatments, have black box warnings to them?

Laz, does Rituxan?

[agate]

Since I'm replying before Lazarus has had a chance to reply, it looks to me as if Rituxan has a black box warning. Linda, is this correct?
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I haven't seen any information on how rare IRIS is but I did find this, from a study where 32 people with MS on Tysabri were taken off it for 3-4 months:

Our findings suggest that younger patients with more extensive disease and greater inflammatory activity before natalizumab treatment are at greatest risk for significant relapses after natalizumab therapy. The widespread inflammatory response observed in some of our cases is radiologically similar to the IRIS observed in cases of human immunodeficiency virus–associated PML once normal central nervous system immune function and surveillance is restored.^{Only registered and activated users can see links., Click Here To Register...} As with PML-associated IRIS, some of our patients exhibited widespread gadolinium enhancement along the edge of numerous previously involved areas of demyelination by T2- and T1-weighted imaging ....Immune reconstitution inflammatory syndrome is associated with a rapid reduction in human immunodeficiency virus 1 viral load and a simultaneous rapid rise in CD4⁺ T-lymphocyte counts after institution of highly active antiretroviral therapy.This is thought to create an enhanced immune response to disease-specific antigens, leading to an overproduction of inflammatory mediators in the context of previous immunosuppression. While classically associated with enhanced inflammatory responses to infectious processes, IRIS has also been associated with noninfectious immune-mediated conditions including systemic lupus erythematosus and autoimmune thyroid disorders. A similar mechanism directed against normal myelin antigens is likely at play in some of our cases. Natalizumab therapy is associated with a reduction in cerebrospinal fluid CD4 and CD8 T lymphocytes, CD19 B cells, and CD138 plasma cells and a reduction in the cerebrospinal fluid CD4:CD8 ratio.

The same authors reported a clinical MS relapse in the patient with the highest total cerebrospinal fluid CD4 and CD8 T-cell count after cessation of natalizumab therapy, suggesting that a more rapid return of immune surveillance and function may be associated with IRIS in patients with MS.

The suggestion from our study that this inflammatory response may become more widespread in certain patients with a longer duration of therapy interruption argues for careful monitoring during any planned natalizumab therapy interruption to detect the earliest signs of IRIS. Future studies must determine the relationship between this IRIS, immunoregulatory function, and cell trafficking during and after cessation of natalizumab therapy. For now, clinicians should be aware of this phenomenon and consider strategies to minimize the risk of IRIS after natalizumab discontinuation.

This is an article from 6 years ago. More is probably known by now but so far I haven't found it.

The article, "Immune Reconstitution Inflammatory Syndrome in Patients with Multiple Sclerosis Following Cessation of Natalizumab Therapy," is from JAMA Neurology:

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[SuzE-Q]

Thanks, agate!

I'd be interested to know if patients are informed of this possible issue before going on these meds, if it's a required discussion point.

[agate]

I'll be on the lookout for some answers.

In the meantime, this recent abstract sheds a little more light on the seriousness of IRIS:

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[stillstANNding]

My mother's neighbor was on Rituxan for RA. She had no clue about PML.
ANN

[Lazarus]

Not sure. Will ask. Exhausted from market today. Will look tomorrow.