To conduct an emulated clinical trial evaluating gynecologic complications of multiple sclerosis (MS) disease-modifying therapies (DMTs) in women with MS using the TriNetX global collaborative network.

A growing body of work is linking the use of MS DMTs to infectious and inflammatory conditions of the female genital tract. However, no large studies have investigated the risks of human papilloma virus (HPV) and herpes simplex virus (HSV) positivity, cervical dysplasia, cervical cancer, cervicitis, vulvovaginitis, and Bartholin cysts/abscesses in women with MS on DMTs.

We propensity-score 1:1 matched women with MS on any versus no DMT, by time on therapy and relevant risk factors (age, marital status, race, ethnicity, tobacco use, body mass index, and long-term hormonal contraceptive use). Our vulvovaginitis model also matched for steroid/antibiotic use and hemoglobin A1c. We then estimated risk ratios (RR) and calculated 95% confidence intervals (CIs) to compare outcomes.

After matching, we analyzed 96,466 women with MS. The DMT group had increased risks of all seven outcomes evaluated: HPV positivity (RR 1.66; 95% CI 1.54-1.80; p <0.001), HSV positivity (RR 1.36; 95% CI 1.20-1.53; p <0.001), cervical dysplasia (RR 1.60; 95% CI 1.49-1.70; p <0.001), cervical cancer (RR 1.27; 95% CI 1.07-1.51; p = 0.007), cervicitis (RR 1.50; 95% CI 1.32-1.71; p <0.001), vulvovaginitis (RR 1.32; 95% CI 1.25-1.39; p <0.001), and Bartholin cysts/abscesses (RR 1.63; 95% CI 1.27-2.09; p <0.001) compared to the no DMT group.

MS DMTs are associated with increased risks of gynecologic complications. Clinicians should recognize these potential sequelae of long-term immunomodulation and integrate gynecological counseling and screening into routine MS care.