Drug products: Fumaderm Biogen, Fumaderm Initial, Fumaderm Initial Biogen, Skilarence, Tecfidera
ATC code: D05BX51, L04AX07
Substances: dimethyl fumarate
The effect of dimethyl fumarate in patients with relapsing remitting Multiple Sclerosis has been shown in both men and women although fewer men have been included in the studies. In the CONFIRM study, the proportion of patients with confirmed disability progression at two years was found to be lower in men treated with dimethyl fumarate compared to placebo while the effect was not significant in women. Regarding adverse events, no data with a relevant sex analysis were found.
Multiple Sclerosis (MS) is more common in women than in men [1, 2]. The gender gap in prevalence has been increasing and is today estimated to be two to three times more common in women than in men [1-3].
Several risk factors of MS have been suggested to have a larger impact on women. Sunlight deprivation, vitamin D deficiency, overweight, low urate levels, and smoking are such risk factors that increase the risk more in women than in men. Suggested mechanisms are that smoking yields increased levels of mature peripheral functioning T cells (OKT3+) in women . Men have a worse prognosis and the role of sex hormones have been discussed [1, 2].
In a biomarker study of MS patients (30 men, 70 women) and healthy controls (24 men, 51 women), insulin growth factor binding protein1 (IGFBP1) was higher in women with MS compared to men . The authors suggest this could reflect different MS progression pathways in men and women.
According to the producer patient age or sex do not affect pharmacokinetic properties of dimethyl fumarate . Bodyweight was found to affect the exposure to the drug but has no effect on the efficacy and safety outcomes studied in the pivotal clinical studies according to the producer. No difference in dosing in men and women has been suggested by the producer .
The CONFIRM study, a RCT comparing the effect of dimethyl fumarate and placebo in patients with relapsing-remitting MS (424 men, 993 women), found a lower annualized relapse rate in the dimethyl fumarate groups (0.224 and 0.198 in the BID and TID groups, respectively) compared to those on placebo (0.401) . In another double-blind, placebo-controlled study, the DEFINE study, in patients with relapsing-remitting multiple sclerosis (326 men, 908 women), showed a reduced proportion of patients having relapsed at two years in the dimethyl fumarate group (27% and 26% in the groups treated with 240 mg dimethyl fumarate BID and TID, respectively) compared with placebo (46%) regardless of patients’ sex. Compared to placebo, the proportion of patients with confirmed disability progression at two years was lower in men treated with dimethyl fumarate but not in women .
No studies with a clinically relevant sex analysis regarding adverse effects of dimethyl fumarate have been found.
A study on interaction between dimethyl fumarate and a combined oral contraceptive (norgestimate 250 μg, ethinyl estradiol 35 μg) did not show any interaction . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
In a US study based on questionnaires with a response rate of 44%, women with MS reported better awareness of disease symptoms and were found to express more positive perceptions of their ability to manage therapy with disease modifying drugs than men with MS .
In a survey study of patient risk tolerance in MS treatment 10 259 patients (response rate 53 %, resulting in 1196 men, 4250 women), women, elderly and those caring for dependents had a lower risk tolerance, while individuals with a more pronounced disability had a higher risk tolerance .
Date of litterature search: 2017-12-07
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson