Drug products: Aubagio, AUBAGIO, AUBAGIO®
ATC code: L04AA31
The effect of teriflunomide in patients with relapsing remitting multiple Sclerosis has been shown in both men and women. Regarding adverse events, no data with a relevant sex analysis were found.
Teriflunomide should not be used during pregnancy. Because of the teratogenic risks effective contraception is recommended as long as the teriflunomide concentration is above 0.02 mg/L (up to two years after terminated treatment). More information can be found in Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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.
The pharmaceutical company reports a 23% decrease in clearance in women compared to men. However, dose adjustment is not recommended .
In the TOWER study, a RCT comparing the effect of teriflunomide and placebo in patients with relapsing remitting MS (338 men, 831 women) found a lower annualized relapse rate in the teriflunomide groups (0.39 and 0.32 in the 7 mg and 14 mg groups, respectively) compared to those on placebo (0.50) . No sex divided results were presented. A pre-specified subgroup analysis of the TEMSO study in relapsing remitting MS (303 men, 785 women) found a lower annualized relapse rate in women on teriflunomide compared to placebo . In men, there was a similar trend between teriflunomide and placebo but statistical significance was not reached .
No studies with a clinically relevant sex analysis regarding adverse effects of teriflunomide have been found.
The concentrations of especially ethinylestradiol but also levonorgestrel can increase, with risk of hormonal adverse events . The mechanism is unknown. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Teriflunomide is contraindicated in pregnant women. In women of child-bearing potential, reliable contraception is recommended as long as plasma concentration of teriflunomide is above 0.02 mg/L (which may be several months after last dose) . Even though the risks are considered low, male patients should be aware of possible male-mediated toxicity to the fetus [11,12]. Semen transferred teriflunomide is expected to be 100 times lower than plasma exposure of a corresponding oral dose . Some regulatory authorities recommend that men wishing to father a child should discontinue teriflunomide treatment . 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: 2017-12-15
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson