Patients monitoring during treatment with Dimethyl fumarate (ORP-23)

Document Type : Oral Presentation


Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran


Dimethyl Fumarate (DMF) is a methyl ester of fumaric acid (chemical formula C6H8O4) that is hydrolyzed in the small intestine to the active metabolite monomethyl fumarate, approved for the treatment of RMS, and moderate to severe Psoriasis.
In addition to relative frequencies, we also examined the absolute numbers of the various cell types over time. As expected, DMF led to a decrease in total leukocyte and lymphocyte counts, with a strong reduction in CD4 and CD8 T cells, B cells also decreased, while NK cells and monocytes were minimally affected.
Dimethyl fumarate may cause serious side effects, including allergic reactions. PML, which is a rare brain infection that usually leads to death or severe disability. JCV test or if clinically suspected (Brain MRI with DWI sequence). Among over 500000 cases exposed to DMF 11-13 cases of PML have been confirmed.   
What labs to monitor with DMF?
Obtain a CBC-diff, including lymphocyte count, before initiating treatment with DMF, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated, consider interruption of DMF in patients with absolute lymphocyte counts less than 500 per/ml persisting for more than 6months.
Is it necessary to measure CD4 and CD8 T cells or B cell markers for monitoring of DMF, as we do testing CD19, and CD20 for monitoring of Rituximab?
In conclusion, both B cell and T cell compartments undergo a drastic decrease in mature populations under DMF treatment.
Independent cohorts and serum neuro-filament confirm a DMF/ associated immune phenotype. Serum neuro-filament light chain (NFL) is a blood biomarker in MS specific for neuro-axonal damage (axon and myelin) in MS. Less is caused by inflammatory activity or chronic neurodegeneration.
Clinically and radiologically active patients were identified by both high (NFL) and the predictive population fraction.       
Increased serum NFL reflects acute disease activity (relapse associated worsening) and also PIRA (progression independent of relapse activity).
Combined measurement of NFL in blood as a biomarker of axonal damage and cellular composition as a marker of inflammatory activity will allow discrimination of the different disease aspects and guide therapeutic strategies (DMF).
How do patients with MS should be monitored?                
MRI, which can reveal areas of MS lesions, on your Brain, Cervical and Thoracic cord with and without Gd every 6-12 months, a contrast material to highlight new or active lesions.
How long DMF can be taken?
DMF can be taken for as long as it continues to have clinical benefits and you are not experiencing intolerable or severe side effects. Your disease is not progressing significantly. You are not developing any new T2 or Gd lesions or existing lesions are not enlarging. You are not having an increase in relapse. Your Brain is not atrophying at a faster-than-normal rate. You have not experienced a prolonged reduction in Lymphocyte numbers.  
A recent European review of safety data identified 11 cases of PML with lymphopenia associated with DMF treatment, including 3 cases with mild lymphopenia (lymphocyte counts defined as absolute lymphocyte counts between 800/dl and lower limit of normal).


  • Receive Date: 30 November 2023
  • Accept Date: 30 November 2023