Dimethyl fumarate (DMF), better known under its trade name Tecfidera®, is an MS medication that was awaited with great anticipation a few years ago and was already bestowed with many laurels before approval. I never quite understood this initial hype, but for me it is still a very important drug in practical use. Like glatiramer acetate and interferon-beta, it is considered a basic therapeutic, but has the big advantage (for many patients) that it can be taken as a pill and does not need to be injected.
Its effect is also good – there are even registry studies now that classify dimethyl fumarate as being similar in potency to the S1P modulator fingolimod, which is classified in efficacy category 2 according to current therapy guidelines. And there’s another advantage: Women with MS often want to have children. In such a case, you need medications that don’t cause problems if pregnancy occurs. Dimethyl fumarate does not have approval during pregnancy like interferon-beta and glatiramer acetate. However, due to its short half-life, it is still quite usable in women who want to have children. So, with dimethyl fumarate, a well-functioning drug is available for women who want to have children, which does not need to be injected – and that is an important point in practice.
Unfortunately, dimethyl fumarate often has a significant tolerability problem at the beginning of intake. About 30% of patients complain of gastrointestinal complaints, the so-called gastrointestinal side effects (GI side effects), after taking it. Although these are harmless, they are sometimes so burdensome that the medication has to be discontinued if all countermeasures do not bring relief. This is then disappointing, especially if you have actively decided for dimethyl fumarate because of the advantages mentioned above.
Dimethyl fumarate versus Diroximel fumarate
Accordingly, the approval of diroximel fumarate (Vumerity®) in November 2021 is interesting news. Like dimethyl fumarate, diroximel fumarate is also a so-called prodrug (a precursor drug), which is converted in the body into the actually active substance monomethyl fumarate (MMF). Both dimethyl fumarate (DMF) and diroximel fumarate (DRF) are metabolized into the active monomethyl fumarate, but different metabolites (metabolic products) are produced during metabolism. This difference seems to be responsible for the fact that diroximel fumarate is better tolerated by MS patients with assumed equal efficacy.
In the so-called EVOLVE-2 study (Naismith RT et. al. Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study CNS Drugs 2020; 34(2):185-196), a total of 504 patients were treated with either DMF or DRF. The study period was 5 weeks. Overall, initial treatment with DRF showed fewer gastrointestinal side effects than starting treatment with DMF (34.8% vs. 49%). Overall, fewer DRF patients also discontinued treatment (1.6% vs. 5.6%). These are positive results, but they also show that the problem of GI side effects still plays a role. In any case, the results provide evidence that if dimethyl fumarate is poorly tolerated, a switch to diroximel fumarate should definitely be tried before completely abandoning the treatment concept.
The recommended starting dose of diroximel fumarate is 231 mg (one capsule). According to product information, this should be taken twice daily. After seven days, the dose should then be increased to a maintenance dose of 2 x 462 mg (2 capsules) daily. As with dimethyl fumarate, it may be sensible to carry out this dosing phase even more slowly. So only reaching the maintenance dose of 2 x 462 mg after four weeks. In addition, it is also recommended with diroximel fumarate to take it with a meal for better tolerance.
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Editor’s note: On the AMSEL Facebook page, you can read what experiences other MS patients have had with dimethyl fumarate in terms of side effects. And what they do about it.
