Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Teriflunomid

Klassificering: A

Preparat: Aubagio, AUBAGIO®

ATC kod: L04AA31

Substanser: teriflunomid

Sammanfattning

Vid skovvis förlöpande Multipel Skleros har den skovföreyggande effekten av teriflunomid visats vara bättre än placebo hos både kvinnor och män. Inga data avseende könsskillnader i biverkningar har hittats.

Teriflunomid ska inte användas av gravida. På grund av den teratogena risken rekommenderas effektiva preventivmedel så länge teriflunomidkoncentrationen är över 0,02 mg/l (upp till två år efter avslutad behandling). För mer information, se kunskapsstödet Janusmed fosterpåverkan.

Additional information

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 [1]. 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 [4]. The authors suggest this could reflect different MS progression pathways in men and women.

Pharmacokinetics and dosing

The pharmaceutical company reports a 23% decrease in clearance in women compared to men. However, dose adjustment is not recommended [7].   

Effects

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) [8]. 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 [9]. In men, there was a similar trend between teriflunomide and placebo but statistical significance was not reached [9].

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of teriflunomide have been found.

Reproductive health issues

The concentrations of especially ethinylestradiol but also levonorgestrel can increase, with risk of hormonal adverse events [10]. 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) [11]. 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 [11]. Some regulatory authorities recommend that men wishing to father a child should discontinue teriflunomide treatment [13]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

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 [5].

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 [6].

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter  innehållande teriflunomid (ATC-kod L04AA31) på recept i Sverige år 2016, totalt 254 kvinnor och 111 män [14].

Uppdaterat: 2019-03-13

Litteratursökningsdatum: 2017-12-15

Referenser

  1. Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler. 2014;20:520-6. PubMed
  2. Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012;8:255-63. PubMed
  3. Johnson KM, Zhou H, Lin F, Ko JJ, Herrera V. Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year. J Manag Care Spec Pharm. 2017;23:844-852. PubMed
  4. Al-Temaimi R, AbuBaker J, Al-Khairi I, Alroughani R. Remyelination modulators in multiple sclerosis patients. Exp Mol Pathol. 2017;103(3):237-241. PubMed
  5. Vlahiotis A, Sedjo R, Cox ER, Burroughs TE, Rauchway A, Lich R. Gender differences in self-reported symptom awareness and perceived ability to manage therapy with disease-modifying medication among commercially insured multiple sclerosis patients. J Manag Care Pharm. 2010;16:206-16. PubMed
  6. Fox RJ, Salter A, Alster JM, Dawson NV, Kattan MW, Miller D et al. Risk tolerance to MS therapies: Survey results from the NARCOMS registry. Mult Scler Relat Disord. 2015;4(3):241-9. PubMed
  7. Cada DJ, Demaris K, Levien TL, Baker DE. Teriflunomide. Hosp Pharm. 2013;48:231-40. PubMed
  8. Confavreux C, O'Connor P, Comi G, Freedman MS, Miller AE, Olsson TP et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13:247-56. PubMed
  9. Miller AE, O'Connor P, Wolinsky JS, Confavreux C, Kappos L, Olsson TP et al. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Mult Scler. 2012;18:1625-32. PubMed
  10. Aubagio (teriflunomide). EPAR - Product Information. European Medicines Agency (EMA); 2017.
  11. Aubagio (teriflunomide). Summary of Product Characteristics. European Medicines Agency (EMA); 2017.
  12. Rozman B. Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet. 2002;41:421-30. PubMed
  13. Kieseier BC, Benamor M. Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis. Neurol Ther. 2014;3:133-8. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2016 [cited 2017-06-20.] länk

Författare: Sebastian Ek

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson