Sex-Related Gap in the Use of Disease-Modifying Therapies in Multiple Sclerosis

In women with multiple sclerosis (MS), the therapeutic strategy may be influenced by the anticipation of future pregnancies, leading to underexposure to disease-modifying therapies (DMTs) and highly effective DMTs (HEDMTs) compared with men. We aimed to evaluate potential therapeutic inertia in women with MS and explore its causes.

We performed a retrospective cohort study based on data extracted on June 2023 from the Observatoire Français de la Sclérose en Plaques for all patients with a relapsing-remitting MS onset between 18 and 40 years. The primary outcome was the annual probability of receiving a DMT, accounting for sex, disease severity, and pregnancy/postpartum periods. Secondary outcomes were the annual probability of receiving a HEDMT, each DMT separately, and interaction of the effect of sex with calendar year, patient age, and disease duration. We used a longitudinal logistic model with generalized estimating equations and an inverse-probability-of-censoring weighting.

We included 22,657 patients with MS; 16,857 (74.4%) were female, mean (SD) age at onset was 29.0 (6.0) years, and median (interquartile range) follow-up duration was 11.6 (6.6-17.3) years. Women were significantly less likely to receive a DMT (odds ratio [OR] 0.92, 95% CI 0.87-0.97) or a HEDMT (OR 0.80, 95% CI 0.74-0.86). This difference appeared 2 years after disease onset for DMTs and 1 year for HEDMTs, and did not differ significantly according to patient's age. Teriflunomide, sphingosine-1-phosphate receptor modulators, and anti-CD20s were significantly underused in women throughout their entire period of availability; interferons β (IFN-β) and natalizumab were initially less used and then equally after some time; glatiramer acetate and fumarates were first used equally, then more frequently in women. The proportion of treated women, analyzed from the first childbirth of 5,268 women, began to decline 18 months before childbirth, from 42.6% to 27.9% at the estimated time of conception.

Women with MS were significantly less exposed to DMTs compared with men. Anticipation of pregnancy was probably an important factor underlying this difference, but also sex-specific therapeutic inertia. Neurologists and patients should be educated on the most recent recommendations on the use of DMTs in the context of pregnancy to avoid deleterious therapeutic inertia.