Author Topic: Tecfidera-associated lymphopenia: Risk factors, clinical significance  (Read 253 times)

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Offline agate

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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.

The abstract can be seen here.
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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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 21.210.9 (range 6-35) months. Prior to dose reduction, average lymphocyte counts were 0.630.16 k/μL, and after six months of dose-reduced DMF treatment,
lymphocytes increased to 0.830.23 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.
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.