Skyrizi vs Fumaderm for psoriasis

[Fred]

This phase three study compared Skyrizi (risankizumab) with Fumaderm (fumaric acid esters)

Quote:

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Background:
In a phase 3 clinical study, patients from Germany with moderate to severe psoriasis who were naïve to systemic treatment and received risankizumab had greater and more rapid disease improvements compared with those who received fumaric acid esters (FAEs).

Objective:
To evaluate patient‐reported outcomes (PROs) in patients treated with risankizumab compared with FAEs.

Methods:
Adult patients were randomized 1:1 to receive either risankizumab 150 mg subcutaneous injections at Weeks 0, 4, and 16 or FAEs (Fumaderm®) provided according to the prescribing label. PRO secondary endpoints assessed were Psoriasis Symptom Scale (PSS), Dermatology Life Quality Index (DLQI), 36‐Item Short Form Health Survey, version 2 (SF‐36v2), Patient Benefit Index (PBI), Hospital Anxiety and Depression Scale (HADS), Patient Global Assessment (PtGA), and European Quality of Life 5 Dimensions 5 Level (EQ‐5D‐5L). PROs were assessed at Weeks 0, 16, and 24.

Results:
Sixty patients each were randomized to receive risankizumab or FAEs. A significant PSS improvement was observed with risankizumab versus FAEs at Weeks 16 and 24 for total and psoriasis‐associated redness, itching, and burning scores (P<0.001). DLQI scores were significantly lower (reflecting better health‐related quality of life) with risankizumab versus FAEs, with least squares (LS) mean differences of −7.4 and −7.6 at Weeks 16 and 24, respectively (both P<0.001). Patients randomized to risankizumab also had larger improvements in SF‐36 Physical and Mental Component Summary scores, HADS anxiety and depression scores, PtGA, and EQ‐5D‐5L index and visual analog scale scores (all P≤0.002) at Weeks 16 and 24 compared with FAEs. PBI was significantly higher, indicating greater benefit, with risankizumab versus FAEs, with an LS mean difference of 1.1 and 1.3 at Weeks 16 and 24, respectively (both P<0.001).

Conclusions:
Risankizumab provides significant benefits over FAEs in improving PROs across several dimensions in patients with moderate to severe psoriasis.

Source: onlinelibrary.wiley.com

*Early view funding unknown

Skyrizi (risankizumab)

Fumaderm

[jiml]

I wonder what the long term results would be after one year, five years or longer
It's a strange comparison as it's a known fact that the build up with FAE's is slow starting on low dose and building up

I accept it might be less fraught with side effects at the start but would have liked to see the study carried out over a longer period.
A you can tell I'm a great FAE lover as its given me the clearest 8 years of my life free from 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.

[Kat]

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.

[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.

[Kat]

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.

Okay so this part I understand. 

I guess there is still confusion and or disagreement within the medical community as to certain things with psoriasis.  The majority thinking that it is an auto immune disease if I understand correctly.  But  Dr. Schweckendieck has a different theory but as of right now it's a theory (based on his studies) right?  Not saying what is correct or incorrect, simply again getting it sorted in my non scientific brain.

But, unless I read it wrong doesn't this study show Skyrizi had better outcomes in their study over DMF?  With DMF you say the "cytokines are less produced and you can imagine that the overactiveness of the immune system slows down and the Psorasis disappears"  But if this study is to be believed, that wouldn't be true of everyone.  Or am I overthinking here?

I think from what I've read more on this forum (including a lot of your information!!) is that DMF works well for some and biologics works well for others.  I don't know if/when/how psoriasis forms but it seems that both are effective treatments just individually one may work better than the other (as in for each individual person).  That's my views on it, but I constantly remind you all that I don't know what I'm talking about 

[Caroline]

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.

Okay so this part I understand. 

I guess there is still confusion and or disagreement within the medical community as to certain things with psoriasis.  The majority thinking that it is an auto immune disease if I understand correctly.  But  Dr. Schweckendieck has a different theory but as of right now it's a theory (based on his studies) right?  Not saying what is correct or incorrect, simply again getting it sorted in my non scientific brain.

But, unless I read it wrong doesn't this study show Skyrizi had better outcomes in their study over DMF?  With DMF you say the "cytokines are less produced and you can imagine that the overactiveness of the immune system slows down and the Psorasis disappears"  But if this study is to be believed, that wouldn't be true of everyone.  Or am I overthinking here?

I think from what I've read more on this forum (including a lot of your information!!) is that DMF works well for some and biologics works well for others.  I don't know if/when/how psoriasis forms but it seems that both are effective treatments just individually one may work better than the other (as in for each individual person).  That's my views on it, but I constantly remind you all that I don't know what I'm talking about 

Well I think you are absolutely right. Psoriasis is a very individual disease and everyone has an immune system of his own which are all different. Think of Covid, there are some that become very ill and others that hardly remark that they are ill. All the results of the difference in immune system.

So... there will be people for whom DMF will not work, as we are all different there are people for whom the mechanism of adding fumarates to the citric acid cycle, either has no result or does not succeed.
Identical this probably is so with Skirizi. The advantage of Skirizi is that you will reach the conclusion faster as it works much faster than the slow process of DMF.

And indeed there is a difference in thinking also. The majority thinks it is an auto-immune disease, but they cannot prove that, as the typical element of auto-immune diseases, anti-bodies, cannot be found.
Schweckendieck was working on psoriasis in the 1970-80 -ties, there were no biologicals then. He was also a chemist and must have been able to find out that there was pyruvic acid involved. By trying the antagonist, fumaric acid, he found out that this worked for Psoriasis. It is a logical way of thinking and perhaps half by accident he was able to solve his own psoriasis.
Of course I cannot exactly guess his thinking, but this is a reconstruction of the most logical line of thinking.
If you look into the fluid you can take out of the joints of someone with Psoriatic Arthritis, then you can find piruvic acid crystals. This immediately also explains the pain and reason for inflammation.

[Kat]

Interesting! Thanks for the discussion Caroline.

Also you said:

"The advantage of Skirizi is that you will reach the conclusion faster as it works much faster than the slow process of DMF."

That helped me understand what you meant earlier (you may have said it then too, sometimes it takes a bit to sink in)

A long term study would be interesting to find out how (if/when/why) the results change.

[Caroline]

Interesting!  Thanks for the discussion Caroline.

Also you said:

"The advantage of Skirizi is that you will reach the conclusion faster as it works much faster than the slow process of DMF."

That helped me understand what you meant earlier (you may have said it then too, sometimes it takes a bit to sink in)

A long term study would be interesting to find out how (if/when/why) the results change.

Yes, that would be interesting. It’s just what Jim also said. Doubt however if that will happen. Pharmacy will not do it, there is no advantage in it. They earn a lot more on Skirizi

[Fred]

I'll chip in for a change.

#1 The DMF gang will always say DMF is better.

#2 Most of the DMF gang have not experienced debilitating psoriasis or psoriatic arthritis. 

#3 Yes obviously the survey is biased and my guess is that is funded by the makers Skyrizi. But Fumaderm or any other DMF like Skilarence can do their own comparisons, what you have to ask is why don't they ?

I'm not saying DMF doesn't work as we have members that have proved that it does indeed work, but there are not many if any comparisons run the other way around. Yes it works but going by our members that are using it, and I mean no offence but apart from Bill none have what I would class as really bad symptoms.

Yes it works but just like all treatments none of them are the best and it's about finding the best for you.

Look at it like Windows vs Apple and you will get what I'm saying.