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   DIR Return to: TECFIDERA (dimethyl fumarate, BG-12, Fumaderm)
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       #Post#: 998--------------------------------------------------
       Tecfidera-associated lymphopenia: Risk factors, clinical signifi
       cance
       By: agate Date: November 10, 2015, 11:21 am
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       From PubMed, November 10, 2015:
       [quote]Mult Scler J Exp Transl Clin. 2015 Jan-Dec;1.
       Dimethyl fumarate-associated lymphopenia: Risk factors and
       clinical significance
       Longbrake EE1, Naismith RT2, Parks BJ2, Wu GF2, Cross AH2.
       Author information
       1Washington University in St. Louis, Department of Neurology,
       660 S. Euclid Ave., Campus Box 8111, St. Louis, MO 63110, USA.
       2Department of Neurology, Washington University in St. Louis,
       USA.
       BACKGROUND:
       Dimethyl fumarate (DMF), a disease-modifying therapy for
       multiple sclerosis (MS), causes lymphopenia in a fraction of
       patients. The clinical significance of this is unknown. Several
       cases of progressive multifocal leukoencephalopathy in
       lymphopenic fumarate-treated patients have raised concerns about
       drug safety. Since lymphocytes contribute to MS pathology,
       lymphopenia may also be a biomarker for response to the drug.
       OBJECTIVE:
       The objective of this manuscript is to evaluate risk factors for
       DMF-induced lymphopenia and drug failure in a real-world
       population of MS patients.
       METHODS:
       We conducted a retrospective cohort study of 221 patients
       prescribed DMF at a single academic medical center between March
       2013 and February 2015.
       RESULTS:
       Grade 2-3 lymphopenia developed in 17% of the total cohort and
       did not resolve during DMF treatment. Older age (>55), lower
       baseline absolute lymphocyte count and recent natalizumab
       exposure increased the risk of developing moderate to severe
       lymphopenia while on DMF. Lymphopenia was not predictive of good
       clinical response or of breakthrough MS activity on DMF.
       CONCLUSIONS:
       Lymphopenia develops in a significant minority of DMF-treated
       patients, and if grade 2 or worse, is unlikely to resolve while
       on the drug. Increased vigilance in lymphocyte monitoring and
       infection awareness is particularly warranted in older patients
       and those switching from natalizumab.[/quote]
       The abstract can be seen here
  HTML http://www.ncbi.nlm.nih.gov/pubmed/26550483.
       #Post#: 1686--------------------------------------------------
       (AAN abst.) Effect of Tecfidera dose reduction on lymphopenia in
        RRMS
       By: agate Date: May 16, 2017, 4:28 pm
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       Presented at the annual AAN conference in Boston, April 2017:
       [quote]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. [/quote]
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