Fumaric acid esters

What are fumaric acid esters?

The fumaric acid esters (FAE) monoethyl fumarate (MEF) and dimethyl fumarate (DMF) are chemical compounds derived from the base compound fumaric acid. Fumaric acid is a food additive commonly found in sweets and cakes. In this chemical state, fumaric acid is poorly absorbed and passes directly through the body without causing any effect. On the other hand, fumaric acid esters are powerful chemicals or drugs that have been used to treat psoriasis for over 30 years. However, in the past decade alone, serious clinical research has been conducted to determine its use, effectiveness, and safety in the treatment of psoriasis and other skin conditions.

It is important to emphasize the difference between fumaric acid and fumaric acid esters. Fumaric acid formulations are available as health supplements and are often marketed as a natural alternative medicine to treat psoriasis. They are poorly absorbed by the intestine and are excreted through the urine without having therapeutic any effect.

What is the history of fumaric acid esters?

The use of fumaric acid esters in the treatment of psoriasis was first introduced in the late 1950s by the German chemist Schweckendiek. A standardized fumaric acid protocol for psoriasis was developed and AED was used both orally and topically (ointment and bathe solution) The results were promising but were associated with serious side effects.

At the time, psoriasis was thought to be caused by a biochemical defect of the citric acid cycle (Krebs), of which fumaric acid plays a role. Although the mode of action of AEDs and their place in psoriasis therapy remains unclear, the evidence suggests that it has nothing to do with the Krebs cycle and the main active compound appears to be dimethyl fumarate (DMF). This is believed to work by correcting the immune imbalance that exists in psoriasis (change from a Th1 pattern of immune response to a Th2).

Who uses fumaric acid esters?

Fumaric acid esters have been used to treat severe psoriasis in Northern Europe for more than 20 years. However, the use of FAE remains unregistered in most countries outside of Germany. The Fumaderm® product is composed of dimethyl fumarate and calcium, magnesium and zinc salts of fumarate monoethylhydrohydrate and has been approved for oral use in Germany since 1994. A second oral product, Skilarence® was introduced to the European market for the treatment of psoriasis in 2017.

Many recent studies have shown that AEDs are an effective therapy in patients with severe psoriasis who have tried and failed conventional psoriasis treatments. Patients tolerating AED therapy can expect 75% improvement in their psoriasis within four months. Additionally, AEDs are being used in combination with second-line medications such as cyclosporine, methotrexate, and hydroxyurea for additional benefit or to facilitate dose reduction of the second-line agent.

What are the side effects of fumaric acid esters?

The main side effect that causes a high dropout rate in most clinical trials is gastrointestinal complaints, which occur in up to 60% of patients. Gastrointestinal problems manifest as diarrhea, nausea, and stomach cramps and pain. Furthermore, redness occurs in the 30% of patients and is worse at the beginning of therapy.

Other more serious side effects that have occurred include kidney and liver abnormalities and abnormalities in white blood cells (lymphopenia, eosinophilia) It is essential that kidney function, liver function, and blood count are regularly monitored when taking AEDs. These changes appear to be reversible when treatment is discontinued, and to date, there have been no reports of serious, long-term serious. toxicity.

More studies are required to determine exactly how AEDs work in psoriasis. Dimethyl fumarate appears to be the primary active ingredient, and further research to refine the currently available FAE formulation may reduce the side effect profile and make it a more acceptable treatment for psoriasis.

Although dimethyl fumarate is a current Sensitizer known to cause contact allergy dermatitis, systemic Contact dermatitis has not been reported in oral treatment with fumaric acid esters.