Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (2019) Karhan, Unutmaz et al

Badpack said:
In no universe its the same cost as Rituximab lol haha. One dose of Rituximab 500mg is around 2000€ and it last for 3-6 months. One dose of Lemtrada cost 20000€ and it last for 3 days.

https://multiplesclerosis.net/living-with-ms/lemtrada-economics-ms-treatments/
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I saw the site you posted on this. This is some sort of swindle set up by the drug company, which does not surprise me unfortunately. The manufacture cost of Campath is similar to rituximab and the cost for a trial should therefore be similar Moreover, one infusion of Campath will produce a major reduction in T cell numbers for ten years (not 3 days). So even if it was ten times as expensive as rituximab per infusion it would be similar in the long term.
 
That dialogue worries me a bit since the question posed by qua sar doesn't make much immunological sense. T cells are not involved in the removal of B cells after rituximab (except maybe CD57+) and lymphoma B cells tend to lose the ability to interact meaningfully with T cells.
 
butter. said:
These findings seem a bit weird to me, these are the kind of things we would have found 20 years ago, no?.
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The less innovative your methods, the more grant money goes directly to your salary or raises, equip for other projects, “editing” your manuscript, and more $ for post-doc grunts.

Plasma measurements of t-cells do not necessarily reflect their ability to enter target tissues, they can be gated by actual physical bottlenecks in the vascular epithelium or just an aberration where they can’t reach the target tissue and still are not able to provide negative feedback so their value is within the norm.

Usually it would be a linear relationship between plasma dose and target dose tissue but it doesn’t need to be, as an exceptional heuristic, almost every neurological illness in the history of medicine.

T-cell reduction writ large will cause patients to worsen because heretofore all evidence suggests some degree of t-cell exhaustion even if it is an artifact (common in repeated stress exposure). This is why immunostimulatory IFN and ampligen were marginally effective, but only partially because while they stimulate t-cells they directly affect centers for wakefulness.

The worsening part will just be ADRs like in healthy patients.
 
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i know that it is a disgusting company move but they wont just give it away for the original price just because you would like them to. Even further, i would expect them to increase the price even more should it really help ppl with Cfs. "Oh, ah new disease we can treat ? Lets just reply it again. Worked great last time. Lets try 100.000€ for a dose this time"
 
Badpack said:
i know that it is a disgusting company move but they wont just give it away for the original price just because you would like them to. Even further, i would expect them to increase the price even more should it really help ppl with Cfs. "Oh, ah new disease we can treat ? Lets just reply it again. Worked great last time. Lets try 100.000€ for a dose this time"
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Campath must be out of patent now. There are companies doing generics of most these monoclonals.
 
I have a friend with MS, who I've realised was due to have several infusions of this same drug – she'd told me the generic name, which is why I didn't recognise it. It was then put on hold whilst some kind of safety review goes on, and she now has no idea whether or not she'll be able to have it. Nothing's ever straightforward... :rolleyes:
 
Snow Leopard said:
Wow! Why is Campath much more potent than Rituximab?
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It isn't. It is just that we make a billion new B cells every day but after twenty hardly any new T cells. So B cell depletion lasts for as long as the marrow precursor are blocked by the drug and no longer. T cell depletion lasts almost for ever in some people.

I don't understand why patients are being given Campath repeatedly for MS though. But the drug companies are quite capable of licensing nonsense regimens to make money.
 
Jaybee00 said:
Lemtrada underwent review by EMA, who restricted use—final approval by EC pending.

Sounds a bit scary. You can get severe neutropenia with this med as well.
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I think this reflects three things:

1. Lemtrada is not actually that good an idea for MS, either theoretically or on evidence base of risk/benefit.

2. All these drugs can rarely cause serious problems.

3. Drug companies are often deliberately putting out scary messages in order to try to restrict usage to conditions where litigation is least likely to cause problems with making money.

But these drugs are certainly no more scary than cyclophosphamide, which is about as toxic as you can get and has a very poor risk/benefit profile these days.
 
Thanks. But T cells still come back after Campath treatment. These new T cells are less likely to be “problematic” like the old ones were because the reconstituted T cells are different/better?

that differential reconstitution of T cell subsets and selectively delayed CD4+ T cell repopulation following alemtuzumab-induced lymphopenia may contribute to its long-lasting suppression of disease activity.
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These findings suggest that an alemtuzumab-mediated increase in the proportion of Treg cells may play a role in promoting the long-term efficacy of alemtuzumab in patients with multiple sclerosis.
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https://www.jimmunol.org/content/191/12/5867

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893855/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231011/
 
Jaybee00 said:
Thanks. But T cells still come back after Campath treatment. These new T cells are less likely to be “problematic” like the old ones were because the reconstituted T cells are different/better?
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T cells do gradually reappear, over many months and years.
Whether or not they are less problematic I am unclear. Most of the T cell theorising about human MS looks to me to be highly dubious, based on unrelated T cell driven animal models. Pretty much all papers on the immunology of MS perpetuate myths with no reliable basis in man. I doubt there is actually anything wrong with the T cells in people with MS. But T cells will get caught up in errors in B cell dynamics, so depleting T cells may give some respite.

I doubt T regs have anything to do with it. Everyone tries to implicate T regs because they are trendy (or were) and people like to get grants to work on them.
 
Jonathan Edwards said:
It isn't. It is just that we make a billion new B cells every day but after twenty hardly any new T cells. So B cell depletion lasts for as long as the marrow precursor are blocked by the drug and no longer. T cell depletion lasts almost for ever in some people.
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Is this simply due to the low survival/selection rate of cells to become naive T-cells in the thymus, along with the steady decline in thymus size due to age, or something else?
 
I find it interesting that a lot of young ppl can be cured/benefit a lot from a proper Immunotherapy early on like iv igG. Always kept me thinking about whats the big difference here. Must be something about the t-cells and the thymus which stops working and just becomes at fatty mass at around 18y.
 
Jonathan Edwards said:
I think new T cell genesis just drops right off in adulthood.
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If not in the thymus, then why do progenitor cells favor differentiation into other lymphocytes? It also begs the question on how to increase the differentiation rate into T cells for therapeutic purposes (recovery from T-cell depletion therapy at the very least).
 
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Snow Leopard said:
If not in the thymus, then why do progenitor cells favor differentiation into other lymphocytes? It also begs the question on how to increase the differentiation rate of T cells for therapeutic purposes (recovery from T-cell depletion therapy at the very least).
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Yes, I think it is in the thymus. I presume that bone marrow-based progenitors do not give rise to T cells.

Edit: reviews on this are a bit confusing, because bone marrow stem cells give rise to T cell precursors early on. I guess the question is whether the bone marrow stops producing T precursor in adulthood or the thymus stops converting precursors into T cells. I don't know the answer to that.
 
Jonathan Edwards said:
It isn't. It is just that we make a billion new B cells every day but after twenty hardly any new T cells. So B cell depletion lasts for as long as the marrow precursor are blocked by the drug and no longer. T cell depletion lasts almost for ever in some people.

I don't understand why patients are being given Campath repeatedly for MS though. But the drug companies are quite capable of licensing nonsense regimens to make money.
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Jonathan Edwards said:
I think new T cell genesis just drops right off in adulthood.
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Slightly scary i.e. a drug trial that wipes your T-cells for ever!
 
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