Dimethyl Fumarate vs Fingolimod for MS: Which Has a Better Safety Profile?

Dimethyl fumarate compared with fingolimod has a better safety profile with less risk for progressive multifocal leukoencephalopathy, infections, transaminitis, malignancy, and macular edema.

Fingolimod as compared with dimethyl fumarate has an increased risk for infection among patients with relapsing multiple sclerosis (MS), according to study results presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held from May 31 to June 3 in Aurora, Colorado.

Disease-modifying therapies (DMTs) are one of the approved treatments for relapsing MS. While DMTs have advanced individualized therapy for patients, selecting the appropriate DMT is a challenge due to limited comparative safety data.

Researchers conducted a pharmacovigilance study to compare the safety of 2 DMTs, dimethyl fumarate and fingolimod, using the FDA’s Adverse Event Reporting System (FAERS) database. 

Data was collected from the FAERS database in October 2022 and adverse event (AE) reports were gathered based on the most common AEs in the package insert. Clinician-reported serious AEs were included in the analysis and self-reported AEs were excluded. The researchers excluded events that could be attributed to other medications the patients were taking.

Comparative safety data between FTY and DMF are presented and demonstrate a safety advantage of DMF over FTY …

Data was standardized to patient-years (PYs) for each dimethyl fumarate. Data for dimethyl fumarate (PY, 1,267,327) was reported in June 2022 and fingolimod (PY, 1,038,100) was reported in August 2022. The researchers reported data as the number of AE cases per 1000 PY. 

The rate of progressive multifocal leukoencephalopathy was 0.118 for fingolimod and 0.026 for dimethyl fumarate (rate ratio [RR], 4.51; P <.001).

The rates of infection for fingolimod and dimethyl fumarate, respectively, were:

  • viral infection, 0.077 vs 0.022 (RR, 3.49; P <.001); 
  • fungal infection, 0.032 vs 0.007 (RR, 4.476; P <.001); 
  • herpes infections, 0.430 vs 0.073 (RR, 5.855; P <.001); and
  • cryptococcal infection, 0.039 vs 0.0024 (RR, 16.278; P <.001). 

The liver function tests were 0.298 for fingolimod and 0.017 for dimethyl fumarate (RR, 17.147; P <.001). Rates of malignancy were reported as 2.43 for fingolimod and 0.95 for dimethyl fumarate (RR, 2.568; P <.001). 

Lastly, other significant rates reported for fingolimod and dimethyl fumarate, respectively, were:

  • macular edema, 0.489 vs 0.002 (RR, 206.725; P <.001);
  • flushing, 0.077 vs 0.391 (RR, 0.197; P <.001); and
  • angioedema, 0.017 vs 0.024 (RR, 0.733; P =.291).

There were no significant differences in rare angioedema complications between fingolimod and dimethyl fumarate. 

The researchers concluded, “Comparative safety data between FTY [fingolimod] and DMF are presented and demonstrate a safety advantage of DMF over FTY in terms of risk of progressive multifocal leukoencephalopathy, viral infections, herpes infections, transaminitis, malignancy, macular edema, and cryptococcal infection, while DMF is expectedly associated with more flushing than FTY.”

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


Roman C, Hersh CM, West T, Sillau SH, Alvarez E. Real-world safety of dimethyl fumarate and fingolimod: a pharmacovigilance study of the FDA adverse event reporting system. Abstract presented at: CMSC 2023; May 31-June 3, 2023; Aurora, CO. Abstract DMT29.