Dimethyl Fumarate Safe and Effective Over Years of Use in Multiple Sclerosis

Real-world use of dimethyl fumarate (DMF) over 5 years resulted in a significantly reduced annualized relapse rate (ARR) without increasing the risk for new safety concerns in patients with multiple sclerosis (MS), according to research presented at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), held October 25-28, 2021 in Orlando, Florida.

Data from the active ESTEEM trial (NCT02047097) were included in this 5-year safety and efficacy analysis of DMF therapy in patients with MS. Participants in this real-world study were recruited from approximately 380 sites. Researchers focused their primary objective on the incidence, type, and pattern of serious adverse events (AEs) as well as AEs that led to discontinuation. Additionally, they assessed the efficacy of DMF on the ARR as well as patient-reported outcomes (PROs).

At the time of data cutoff, a total of 5084 patients (mean age, 40.0 years; 74% female) with MS in the trial had received ≥1 dose of DMF and were therefore included in the analysis. A total of 1506 patients were treated for 24 to 48 months, while 441 patients were treated for ≥48 months.

The overall rate of serious AEs was 4.8% (n=245), with infections (1.3%) and nervous system disorders (<1%) being the most common serious events. Approximately 19.0% (n=965) of patients discontinued DMF because of AEs, which were primarily related to gastrointestinal disorders (7.8%).

In the overall population, the model-based ARR for 1 year before vs 5 years after DMF exposure was 0.82 (95% CI, 0.80-0.84) vs 0.09 (95% CI, 0.09-0.10), which represented an 88.6% reduction in the ARR with DMF (P <.0001). In the newly diagnosed population (n=1447), the model-based ARRs were 1.12 (95% CI, 1.08-1.16) for 1 year before DMF initiation vs 0.10 (95% CI, 0.09-0.11) for the 5 years after DMF treatment, representing a 91.3% reduction in ARR (P <.0001).

For the 2364 patients in the early MS group (ie, those with ≤1 prior DMT who started DMF ≤3 years of diagnosis), the ARRs for 1 year prior and 5 years after DMF treatment were 1.03 (95% CI, 1.00-1.06) and 0.10 (95% CI, 0.09-0.11), which represented a 90.3% reduction in ARR (P <.0001). Additionally, in the patients who received IFN/GA at any time from MS diagnosis (n=2976), the ARRs were 0.69 (95% CI, 0.66-0.72) for 1 year before DMF therapy vs 0.09 (95% CI, 0.08-0.10) for 5 years after DMF, corresponding with an 86.5% reduction in ARR (P <.0001).

The researchers noted that Kaplan-Meier estimated that the probabilities of the overall population and the newly diagnosed patients without a relapse at the 5-year follow-up period were 71.1% and 75.8%, respectively. The PROs, according to the researchers, were “generally stable” across all subgroups up to 48 months.

“These data provide further evidence of real-world effectiveness of DMF in patients early in their MS disease course,” they concluded.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Pandey K, Giles K, Balashov K, et al. Real-world safety and effectiveness of delayed-release dimethyl fumarate in relapsing multiple sclerosis patients: Interim results from ESTEEM. Presented at: CMSC 2021 Annual Meeting; October 25-28, 2021; Orlando, Florida. Abstract DMT40.