Discontinuation of Dimethyl Fumarate for MS: Reasons and Rates Vary Based on Sex

Major differences exist between multiple sclerosis (MS) sites in reasons for and rates of discontinuing dimethyl fumarate treatment. Furthermore, compared with men, women with MS are more likely to discontinue treatment. These are the findings of a Danish nationwide population-based study published in Multiple Sclerosis and Related Disorders.

Adherence to disease-modifying treatment (DMT) in MS is reported to range between 12% and 59%. Switching between DMTs is associated with delayed efficacy and increased healthcare costs.

To evaluate motivations for dimethyl fumarate discontinuation, researchers sourced data for this study from the Danish Multiple Sclerosis Registry which collected information from 13 MS clinics in Denmark. The researchers assessed patients (N=2448; mean age, 36; 75.7% women) who received dimethyl fumarate treatment between 2014 and 2020 for discontinuation. Patients started dimethyl fumarate treatment 5.5 years after MS diagnosis, and 32.7% were treatment naïve at dimethyl fumarate initiation.

At the end of the study period, 49.2% of patients remained on dimethyl fumarate and 50.8% stopped for any reason. The dimethyl fumarate discontinuation rate was:

• 85% at 6 months,
• 70% at 12 months,
• 60% at 24 months, and
• 40% at 60 months.

Overall, patients received dimethyl fumarate for an average of 26.4 months and the average duration of dimethyl fumarate treatment among those who discontinued treatment was 16.1 months.

Stratified by clinic, discontinuation rates were significantly higher at sites 1 (hazard ratio [HR], 2.1; CI, 1.6-2.8; P <.001), 3 (HR, 1.7; CI, 1.2-2.4; P <.01), and 9 (HR, 1.5; CI, 1.2-2.0; P <.05) compared with the site with the lowest discontinuation rate (site 7).

Discontinuations were attributed to adverse events (AEs; 52.8%), active disease (25.3%), pregnancy (9.1%), or other reasons (12.8%). A total of 107 patients who discontinued due to pregnancy restarted treatment during postpartum. Rare motivations for discontinuation included inactive disease, contraindications, compliance, and termination of care from the clinic.

Compared with the overall group average, sites 1 (standard residual [SR], 3.8; P <.01), 3 (SR, 3.2; P <.01), and 8 (SR, 2.0; P <.05) had higher rates of discontinuation due to AEs, whereas sites 9 (SR, -4.9; P <.01) and 11 (SR, -3.3; P <.01) had lower rates.

Sites 9 (SR, 3.8; P <.01) and 11 (SR, 3.8; P <.01) had higher rates of discontinuation due to disease activity, whereas sites 1 (SR, -2.2; P<.05), 7 (SR, -2.6; P <.05), and 8 (SR, -2.5; P <.05) had lower rates.

The types of AEs leading to discontinuation also varied by site, in which significant differences in discontinuations due to gastrointestinal, flushing, and lymphopenia AEs were observed.

Compared with men, women were more likely to discontinue due to lymphocytopenia (P =.04) or flushing (P =.04).

These trends may have been biased by the lack of adjustment for gender or age.

“Our results suggest that management strategies during DMF [dimethyl fumarate] treatment can reduce discontinuation rates due to AEs. Further studies are needed to identify specific management strategies and good clinical practice to reduce discontinuation rates in DMF-treated people with MS.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.