Dimethyl fumarate is marketed in Germany under the trade name Tecfidera® by the company Biogen, but is now also available generically (see MS-Docblog). Dimethyl fumarate is approved for the treatment of relapsing multiple sclerosis in adult patients and in children and adolescents from 13 years of age. The standard dosage is 2 x 240 mg/day. To improve tolerability, this dosage is achieved by slowly introducing the medication. Therefore, hard capsules with 120 mg are available for the initial dosage. According to therapy guidelines, dimethyl fumarate is primarily intended for the treatment of mild and moderate forms of progression of MS and, due to its simple oral application, is a popular and frequently used MS medication.
The product information for dimethyl fumarate does not recommend administration during pregnancy and in women of childbearing age who do not use reliable contraception. However, there are already quite reliable registry data suggesting that exposure during pregnancy does not lead to malformations or miscarriages. Therefore, dimethyl fumarate, also due to its short half-life, is considered a suitable preparation for oral MS therapy of mild and moderate MS in women of childbearing age.
Side effects: Gastrointestinal symptoms, flush
Overall, the side effect profile of dimethyl fumarate is manageable. The most problematic point is certainly the gastrointestinal complaints caused by dimethyl fumarate, especially in the initial phase of intake. The complaints are summarized as GI (gastrointestinal) side effects. These include a variety of complaints such as nausea, heartburn, bloating, abdominal pain, diarrhea etc. These symptoms occur in up to 30% of patients in the initial phase. They are also the most common cause for discontinuing the medication prematurely within the first months of prescription. However, the complaints improve with increasing duration of use. After 3 months of application, less than 5% of patients reported relevant GI side effects in the approval studies.
Good patient care during initial application is therefore very important and advisable for dimethyl fumarate. This includes mental support as well as the slow introduction of the substance, taking it with food and possibly treating gastrointestinal symptoms with medication. If the quality of life is permanently impaired by the GI side effects despite good care, dimethyl fumarate is probably not a suitable therapy in individual cases. Just as often as GI side effects, patients complain of a temporary reddening of the skin, also known as “flush” symptoms. The flush is often perceived as a burning sensation or heat. The flush symptoms also decrease with increasing use, they have turned out to be less relevant in everyday life than the gastrointestinal side effects. Both the GI symptoms and the “flush” symptoms are striking tolerance problems that are unpleasant but not dangerous from a medical point of view.
Regularly check differential blood count
A bigger problem is the drop in lymphocytes (a subtype of white blood cells), which is observed in many patients, but rarely very pronounced. In about 6-10% of patients, a relevant drop in lymphocytes is observed. Especially the patients who show a significant drop in lymphocytes to values below 500/µl shortly after intake and are measured so low repeatedly should stop the therapy. But even with a drop in values below 800/µl, it should be controlled and possibly reconsidered the therapy.
In rare cases, the use of dimethyl fumarate has led to the occurrence of progressive multifocal leukoencephalopathy (PML), an opportunistic infection with the JC virus. Currently, 11 cases (as of autumn 2021) are known, which is very low considering more than 500,000 patients treated with dimethyl fumarate. However, the majority of these patients had a long-lasting lymphopenia before the diagnosis of PML, which is why these changes in the blood picture are classified as relevant. Accordingly, the differential blood count should also be regularly checked at the beginning of the therapy. Another commonality of the PML patients was a higher age, so that dimethyl fumarate should be used more cautiously in older patients (> 50 years).
In addition to regular checks of the blood count, it is also recommended to check kidney and liver function in the initial phase, as these laboratory values can show changes when taking dimethyl fumarate.
Overall, apart from the tolerance problems, it is a medically relatively unproblematic substance that has been firmly established for years in the treatment of mild and moderate relapsing MS courses, especially in younger and female patients.
