Oral therapy of multiple sclerosis has become more varied and effective. There are now many injectable and oral treatments, all with the objective of protecting a patient’s brain from inflammation. But physicians and patients have little evidence, as there very few head to head comparisons of the available drugs. A recent study made a comparison of dimethyl fumarate and teriflunomide.

Buron et al. Neurology 2019, 92:e1811-e1820

Kalinick. Neurology 2019, 92:737-738

The results showed dimethyl fumarate is superior. Previous studies had already demonstrated both drugs were superior to placebo. A new study was carried out over 4 years of observation in 2236 Danish patients with MS of the relapses and remissions form. It showed the annualized relapse rate of 0,16 for teriflunomide and 0,09 for dimehtyl-fumarate, a statistically and real-life signficant difference. The effect appeared at one year. Patients on teriflunomide were twice as likely as those on dimethyl fumarate to be taken off treatment because of lack of effect with continued disease activity. Interruption of treatment due to side effects was similar in the 2 groups.

Similar studies of oral therapy of multiple sclerosis carried out in Italy, France and Germany may be summarized to the bottom line that dimethyl fumarate is marginally superior to teriflunomide, with the same toxicity and safety profile. A pattern that has started to emerge is that patiens with no prior exposure to disease modifying and immunotherapies may benefit even more from dimethyl fumarate.

In this field, there is the notion, still without objective evidence, that fingolimod is the next step in oral therapy of multiple sclerosis to these 2 drugs, with more efficacy and more toxicity. Dimethyl fumarate is safe, reduces disease activity with lesser effect on disease progression. Adverse effects are gastrointestinal, flushing and lymphopenia.

Killestein and Reder. Neurology 2019, 92:696-697

As much as in psoriasis, it is this lymphopenia that has been associated with ocasional cases of progressive multiple leucoencephalopathy. The lymphocyte count has been shown to decrease in the first months and to stabilize after one year for many years. The drop is greater in CD8+ when compared to CD4+ T lymphocytes. The absolute lymphocyte count does not appear to be enough to detect the risk of PML and other serious infections. An absolute count of less than 0,5 x 10 (9) /L for more than 6 months, or 0,8 in those positive for JC vírus, has been recommended by the FDA, the European Medicines Agency and some clinicians as the thershold when dimethyl fumarate should be withdrawn.

Dr Paulo Bittencourt

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