Skyrizi vs Fumaderm for psoriasis

[Caroline]

Agreeing with your statement Jim. I would also like to see the comparison over 8 years.

Calling Fumaderm: fumaric acid esters, is exactly right.
Fumaderm is a combination of MEF and DMF. The reason that MEF is added is because it speeds up a little the effect of the DMF, but on the other side it is so toxic that you cannot go above 6x120 mg. It is mainly dangerous for the Kidneys.

Second point.. Fumaderm is nowadays hardly used, it has been replace by the registered medication of Skilarence. Which is only DMF and does not have the drawback of the toxic element. So the research is pointing a little bit next to the target.

Third point: Skirizi is a immuno suppressor of a certain cytokine, it is not a medicine in the healing sense.
DMF/Fumaderm adds a surplus of fumarate into your body. The effect is that the citric-acid cycle in the cells will start working better and will reduce the waste that is produced by the cells where the cycle does not work correctly. This waste causes a series of effects in the body that leads to Psoriasis or Psoriatic Arthritis. So DMF is medication that is closer to “healing”. It does not heal in the sense that it repairs the problem, but it controls the problem.

I concede that you all know more about this than I do!  But a question.  Would an immune suppressor (doesn't alot/all of the biologics fit this category?) also control the problem if it worked for the person?  Just asking as in what you mean with the wording "controls the problem"  I do understand that one targets the immune system and I understand you are saying that DMF/Fumaderm works on the cells.  But if they both work do they not both control the problem? Just trying to understand.

Good question Kat.
There is a different sort of control.
With a (any) biological, there is suppression of certain cytokines (IL-23 an Il-17 mostly). These cytokines cause the psoriasis to appear on your skin or in your joints, because they are there in excess and they stimulate the immune system to be overactive on certain points.
Because of the suppression of the cytokines, the immune system will not be active anymore on that level and the psoriasis disappears.

The theorie of dr. Schweckendieck, followed in the Netherlands by several other doctors, is that the main problem of Psoriasis is a problem in the energy cycle in the cell, called the citric acid cycle. Due to the incomplete burning cycle in the cell, there is a waste product (piruvic acid) and that waste is the cause of the cytokines to increase (several but o.a. IL-23 and/of IL-17), leading to the overaction of the immune system, leading to Psoriasis or Psoriatic Arthritis.
And here we come to the effect of DMF. DMF causes an extra of fumarates (MMF, mono methyl fumarate) to reach the cells. Therefore in the cell the burning increases (most people who use DMF have a slightly higher temperature), because of the increase burning, the citric acid cycle performs better and the emission of the waste reduces. Therefore also the cytokines are less produced and you can imagine that the overactiveness of the immune system slows down and the Psorasis disappears.

So... the difference is the point where you act.
Biologicals suppress the cytokines áfter they have been produced by the body.
DMF prevents the cytokines to appear.

This also explains why DMF always works slowly as it takes time to reach this change in the cells and it takes time to remove the waste which causes the cytokines.
And it explains why biologicals work immediately as it blocks the cytokines immediately.

How dr. Schweckendieck came to this conclusions is more or less logical. In his time there was very little known about the role of cytokines in the immune system. But Schweckendieck was also a chemist and the citric acid cycle was already known. So when Schweckendieck found an excess of piruvic acid he probably reasoned what was wrong and started to treat with the antagonist of piruvic acid, fumaric acid in the form of esters of fumaric acid. By the way, he himself was suffering from psoriasis and tried it on himself.

This all would lead to more conclusions. As there is a sequence in which finally Psoriasis is caused, this suggests that Psoriasis is NOT an auto-immune disease. An auto-immune disease causes the immune system to attack certain elements of the body AND with an auto-immune disease it is always possible to find anti-bodies related to the auto-immune disease.
With Psoriasis it is not possible to find anti-bodies, this makes the diagnosis of Psoriatic Arthritis also that difficult. Whereas rheumatic artritis can be diagnosed much more easily and is also a very different disease.