Oral fumaric acid esters for psoriasis an effects and safety study

[Fred]

Here is an abstract that looked to assess the effects and safety of oral fumaric acid esters for psoriasis.

Quote:

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Background:
Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries.

Objectives:
To assess the effects and safety of oral fumaric acid esters for psoriasis.

Search methods:
We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register.

Selection criteria:
Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis.

Data collection and analysis:
Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects.

Main results:
We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.

One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects.

Authors' conclusions:
Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.

Source: onlinelibrary.wiley.com

*Copyright © 2015 The Cochrane Collaboration.
Author Information
1: Cardiff University, Department of Dermatology & Wound Healing, Cardiff Institute of Infection & Immunity, Cardiff, UK
2: University Hospital of Wales, Welsh Institute of Dermatology, Cardiff, UK
3: Cardiff University, South East Wales Trials Unit, Institute of Translation, Innovation, Methodology and Engagement, Cardiff, Wales, UK
4: Universitätsklinikum Carl Gustav Carus, Department of Dermatology, Dresden, Germany

[Caroline]

Oeeeeeeeeeee !!!!

Very interesting ! Thanks.

By the way.... The monoethylfumarate is completely useless, we over here in NL, know that already for long.

[Fred]

Oeeeeeeeeeee !!!!

Very interesting ! Thanks.  

By the way.... The monoethylfumarate is completely useless, we over here in NL, know that already for long.  

You're welcome, but no good talking to me about it.

[jiml]

Good to see a study on the efficacy of FAE's on psoriasis, although inconclusive and I can agree that the efficacy as far as I know from my experience is as good if not better than methotrexate but the side effects are far more acceptable and not as long lasting .
Hopefully the results of this may encourage more dermatologists here in the UK to prescribe FAE's rather than methotrexate

[Caroline]

Good to see a study on the efficacy of FAE's on psoriasis, although inconclusive and I can agree that the efficacy as far as I know from my experience is as good if not better than methotrexate but the side effects are far more acceptable and not as long lasting .
Hopefully the results of this may encourage more dermatologists here in the UK to prescribe FAE's rather than methotrexate

[Quest4Cure]

It's a new study on an old theory. From what I understand the study means that psoriasis occurred due to a deficiency in fumaric acid levels leading to defects in the citric acid cycle. We're back to our bodies PH. acid or alkaline...6.0 or 7.1 PH...somewhere in that area. Kinda like soil. At least that's part of the history of this theory.

Here's the botanist theory....not much grows in alkaline soils.... Most plants grow in Acid soils or neutral soils. Not too acidly or too alkaline. So add amendments to the soil to achieve solid growing Conditions for the plants to produce the results required. 6.0-7.0 PH. ( medications in some cases with P. )

Why can't we achieve the same thing by drinking virgin margaritas for Acid balance and green slurpies for alkaline balance. Fruits, nuts veggies..ahhhh ??? There are test strips OTC which can identify the Results.

Thanks for the update .

[Caroline]

It's a new study on an old theory. From what I understand the study means that psoriasis occurred due to a deficiency in fumaric acid levels leading to defects in the citric acid cycle. We're back to our bodies PH. acid or alkaline...6.0 or 7.1 PH...somewhere in that area. Kinda like soil. At least that's part of the history of this theory.

Here's the botanist theory....not much grows in alkaline soils.... Most plants grow in Acid soils or neutral soils. Not too acidly or too alkaline. So add amendments to the soil to achieve solid growing Conditions for the plants to produce the results required. 6.0-7.0 PH. ( medications in some cases with  P. )

Why can't we achieve the same thing by drinking virgin margaritas for Acid balance and green slurpies for alkaline balance. Fruits, nuts veggies..ahhhh ??? There are test strips OTC which can identify the Results.

Thanks for the update .

Basically you are right Quest. It seems some kind of deficiency.

But.... it is NO theory. It comes from a very practical approach and is already 50 years old and working. So no theory, pure practical magic.
The fact is that DMF appears to have more effect on our cells than we up to now knew. I have seen an interview with two dermatologists, in dutch so incomprehensible for you , where it appears that not only psoriasis can be targeted, but also MS, Lichen Sclerosis, Crohns, that it even appears to be good for people who have heart problems that it works against bed-sore wounds of elderly people, the practical field in which it can be used seems to widen and widen.

[Quest4Cure]

It's a new study on an old theory. From what I understand the study means that psoriasis occurred due to a deficiency in fumaric acid levels leading to defects in the citric acid cycle. We're back to our bodies PH. acid or alkaline...6.0 or 7.1 PH...somewhere in that area. Kinda like soil. At least that's part of the history of this theory.

Here's the botanist theory....not much grows in alkaline soils.... Most plants grow in Acid soils or neutral soils. Not too acidly or too alkaline. So add amendments to the soil to achieve solid growing Conditions for the plants to produce the results required. 6.0-7.0 PH. ( medications in some cases with  P. )

Why can't we achieve the same thing by drinking virgin margaritas for Acid balance and green slurpies for alkaline balance. Fruits, nuts veggies..ahhhh ??? There are test strips OTC which can identify the Results.

Thanks for the update .

Basically you are right Quest. It seems some kind of deficiency.

But.... it is NO theory. It comes from a very practical approach and is already 50 years old and working. So no theory, pure practical magic.
The fact is that DMF appears to have more effect on our cells than we up to now knew. I have seen an interview with two dermatologists, in dutch so incomprehensible for you   , where it appears that not only psoriasis can be targeted, but also MS, Lichen Sclerosis, Crohns, that it even appears to be good for people who have heart problems that it works against bed-sore wounds of elderly people, the practical field in which it can be used seems to widen and widen.

Right u r ...Yes yes of course it been in studies since the 1950's. Yikes!