Drug products: Tysabri
ATC code: L04AA23
The effect of natalizumab 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.
In our opinion, the present evidence does not motivate differentiation in dosing or treatment between men and women.
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.
No published analysis of pharmacokinetic characteristics in men and women have been found. No difference in dosing in men and women have been suggested by the producer .
In the AFFIRM study, a RCT comparing the effect of natalizumab and placebo in patients with relapsing MS (282 men, 660 women) found natalizumab to be more effective in preventing progression of disability than placebo . However, no sex divided results were presented. Women developed anti-drug antibody (ADA) more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0) according to retrospective data from 3440 patients (987 men, 2453 women) on natalizumab treatment .
No studies with a clinically relevant sex analysis regarding adverse effects of natalizumab have been found.
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (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 . Natalizumab discontinuation is associated with a disease reactivation in MS patients. In a cohort of relapsing remitting multiple sclerosis patients discontinuing natalizumab due to progressive multifocal leukoencephalopathy (23 women, 7 men) concern significant reduction of cognitive impairment index (CII) was found after 1 year. Predictors of cognitive worsening was male sex, disease duration, and the treatment discontinuation .
In a prospective study of MS patients (n=300 on fingolimod, 221 women, 79 men) female sex and prior exposure to natalizumab (n=34) increased the probability of lymphopenia on fingolimod .
MS treatment with natalizumab is associated with Progressive Multifocal Leukoencephalopathy (PML) in patients seropositive for anti-JCV antibodies (JCV+) [11, 12]. In the STRATIFY-1 study, a longitudinal observational study of relapsing MS patients treated or considered for treatment with natalizumab (830 women, 266 men) in the United States, overall anti-JC virus antibody prevalence was 56.0% (95% CI, 53.0-59.0) . Prevalence was significantly lower in women (53.4%; 95% CI, 49.9-56.8) than men (64.3%; 95% CI, 58.2-70.0). Similarly, in a Portuguese study among MS patients (253 women, 118 men), 253 (68%) patients were JCV+ . More men (76%) than women (64%) were JCV+. There were few patients who converted in JCV status and no sex analysis was presented.
Date of litterature search: 2017-12-15
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson