Faculty Collaboration Database

Delayed lymphocyte re-population following discontinuation of dimethyl fumarate and after switching to other disease modifying drug therapies. Mult Scler Relat Disord 2017 Nov;18:60-64

Date

11/17/2017

Pubmed ID

29141823

DOI

10.1016/j.msard.2017.09.014

Scopus ID

2-s2.0-85029860319 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

BACKGROUND: Dimethyl fumarate (DMF) reduces absolute lymphocyte counts, CD4, and CD8 counts, without significantly affecting total white blood cell counts. However, the recovery rate of these cells after discontinuation of DMF is unknown. The effect of subsequent disease modifying therapies (DMTs) on re-population rate is also unknown.

OBJECTIVES: 1. To study the re-population rate of absolute lymphocytes, CD4, and CD8 counts back to baseline after discontinuation of DMF. 2. To measure the effect of subsequent DMTs on the re-population rate of these cells after DMF therapy. 3. To study the effect of the duration of exposure to DMF on repopulation of these cells.

METHODS: A retrospective chart review of subjects who had discontinued DMF and in whom, CBC with differential, CD4 and CD8 counts were available at baseline, discontinuation and at follow-up (n = 113). Linear mixed models were used to analyze and assess linear trends in lymphocyte counts after DMF had been discontinued.

RESULTS: DMF causes a significant drop in absolute lymphocyte, CD4, and CD8 counts. Re-population of these cells after discontinuation of DMF is significantly delayed, irrespective of whether or not a subsequent DMT is used, although there is a difference in re-population rate among DMTs. The re-population rate is also dependent on the duration of time patients have been exposed to DMF; longer exposure was associated with more delayed recovery.

CONCLUSION: During this 30 month study period, re-population rates were significantly delayed post-DMF, irrespective of what subsequent DMT the patients received. Furthermore, no recovery of lymphocyte counts occurred in patients who were started on fingolimod or alemtuzumab after DMF was discontinued; in fact there was a continued decline in all of the cell populations studied.

Author List

Khatri BO, Tarima SS, Essig B, Sesing J, Olapo T

Author

Sergey S. Tarima PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Dimethyl Fumarate
Drug Substitution
Follow-Up Studies
Humans
Immunosuppressive Agents
Linear Models
Lymphocyte Count
Lymphocytes
Multiple Sclerosis
Recovery of Function
Retrospective Studies
Time Factors