Cladribine – oral

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

No studies with a clinically relevant sex analysis regarding pharmacokinetics of cladribine p.o. have been found in the literature searches. The manufacturer reports that population kinetic analysis did not show any sex differences. Oral cladribine is dosed in mg/kg and the manufacturer recommends the same cumulative dose per kilogram in men and women [7].

Effects

Both women and men were included in the pivotal studies and around 2/3 of study participants were women. No sex divided results have been reported and no studies with a clinically relevant sex analysis regarding the effect of cladribine p.o. in MS have been found.

Adverse effects

In the randomized, placebo controlled, multicenter phase III-study CLARITY of cladribine in high activity MS (428 men, 898 women) [8], the incidence of malignancies did not exceed the expected rate in a population standardized for country, sex and age [9].

Reproductive health issues

It is unknown if cladribine interacts with oral contraceptives and the manufacturer recommends that double anticonceptional methods are used for women on cladribine treatment or for female partners to men on cladribine treatment [7]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Highly effective contraception is recommended when using cladribine [7]. 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].