MS Speaks

Dimethyl Fumarate in Relapsing Remitting Multiple Sclerosis: Effects of Dose Reduction on Lymphopenia

Ka-Ho Wong1, Erica Marini1, Stacey Clardy1, L DeWitt1, Julia Klein1, M. Paz Soldan1,2, John Rose1

1
University of Utah, Department of Neurology, 2
Neurology, University of Utah

Objective:

Determine the effects of dose reduction in relapsing-remitting multiple sclerosis (RRMS) patients developing lymphopenia while on dimethyl fumarate (DMF) therapy, and monitor the associated clinical course and MRI outcomes.

Background:

Dimethyl fumarate is an FDA-approved first-line therapy to treat adult patients with RRMS. At the standard dose of DMF 240 mg twice daily, lymphopenia of grade 2 or higher is a risk. Dose reduction may lessen the degree of lymphopenia, but it is not known if reduced dose therapy remains effective under these circumstances.

Design/Methods:

A retrospective chart review was performed on RRMS patients prescribe with oral DMF from the University of Utah Multiple Sclerosis Clinic database from June 2013 to April 2016. Patients on reduced dose DMF due to lymphopenia were identified and included in this analysis.

Results:

Of the 105 patients identified through chart review, dose reduction to DMF 240 mg once per day (or less) was found in 6 patients with a mean duration of therapy of 21.2±10.9 (range 6-35) months. Prior to dose reduction, average lymphocyte counts were 0.63±0.16 k/μL, and after six months of dose-reduced DMF treatment,
lymphocytes increased to 0.83±0.23 k/μL. During this limited period of observation, these patients had no relapses, no new neurological manifestations, and no new or active lesions on brain and spinal cord MRI.

Conclusions:

Reduced dose dimethyl fumarate may offer an opportunity for patients who experience lymphopenia on the standard 240 mg twice daily dose DMF. Our results indicate that reduced dose DMF lessens the degree of lymphopenia, seemingly without compromising efficacy, as evidenced by lack of clinical or MRI disease activity during the 6 months observation period.

These findings suggest that partial dose therapy may be a sufficient
option for some patients. Further observation will be of interest to determine if relapses or MRI activity recur in the future.