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Women with multiple sclerosis (MS) are significantly less likely than men to be treated with disease-modifying therapies (DMTs) and highly effective DMTs (HE-DMTs), a new study showed.

At comparable levels of disease severity, women had 8% lower odds of receiving any DMT and 20% lower odds of receiving HE-DMT. While pregnancy may partially explain undertreatment in women, this doesn’t fully account for the disparity between the sexes.

“When used early, MS drugs can delay the burden of the disease, so women who are not treated could have worse outcomes in the long term and an increased risk of long-term disability. This loss of chance is not acceptable anymore as there are drugs that are compatible with pregnancy or can continue to fight the disease long after people stop them when they are trying to conceive,” study investigator Sandra Vukusic, MD, PhD, University of Lyon in Lyon, France, said in a news release.

The study was published online on July 30 in Neurology.

Most Patients With MS Are Women

The researchers hypothesized that DMTs may be underprescribed in women, particularly during childbearing years, due to potential clinician bias and previously unclear data on the safety of DMTs before, during, and after pregnancy.

Although women make up roughly 75% of patients with MS, a study published last year showed women are more likely to be taken off DMTs and less likely to have treatment escalated than men.

For the study, the researchers reviewed data of 22,657 patients with relapsing-remitting MS between 1997 and 2022 from the Observatoire Français de la Sclerose en Plaques (74.4% women; mean age at onset, 29 years).

The primary outcome was the annual likelihood of each sex prescribed a DMT while accounting for disease severity and periods of pregnancy and postpartum.

The second outcome was the annual probability of patients receiving an HE-DMT or a specific DMT, and how this was influenced by sex, accounting for covariates such as time, age, and disease duration.

To evaluate the potential impact of pregnancy on prescribing patterns, the researchers analyzed treatment rates in relation to time to childbirth; 36.3% of patients had at least one pregnancy.

Data were analyzed using longitudinal logistic modeling with generalized estimating equations and an inverse probability of censoring weighting.

Disturbing Disparities

Before adjusting for variables, investigators found no significant difference in DMT use between men and women.

After adjusting for periods of pregnancy, postpartum, and disease severity, women were significantly less likely than men to receive a DMT (odds ratio [OR], 0.92; 95% CI, 0.87-0.97) and were even less likely to receive an HE-DMT (OR, 0.80; 95% CI, 0.74-0.86).

“Disturbingly, these disparities appeared as early as 1-2 years after disease onset and persisted at least over the first decade of follow-up,” Gabriel Bsteh, PhD, professor and neurologist at the Medical University of Vienna, and Harald Hegen, MD, PhD, researcher at Innsbruck Medical University, both in Austria, wrote in an accompanying editorial.

Women had a higher mean annual relapse rate and were less likely to be prescribed teriflunomide, S1PR modulators, and anti-CD20s.

The number of treated women decreased 18 months before childbirth, from 42.6% to 27.9% around the time of conception and 11.1% at childbirth.

‘A Timely Wake-Up Call’

A limitation of the study was that the data used were from an expert center on MS — the treatment disparity between sexes could be higher in nonexpert settings. Other limitations included a lack of data on potential pregnancy complications related to discontinuing DMT use and feasibility of replicating results in more diverse populations.

“Anticipation of pregnancy was probably an important factor in this difference between women and men with MS, but there could also be a reluctance to use these treatments when they may actually be the best way to manage the disease and delay disability,” Vukusic noted.

Both Bsteh and Hegen called for clinicians to familiarize themselves with the latest guidelines for safe DMT use in pregnancy and increase education for patients. They described the findings as a “timely wake-up call: Even as our therapeutic arsenal expands, sex-based inertia threatens to blunt its benefit for women with MS.”

See article for full list of author disclosures.