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ABSTRACT: Background
Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.Methods
Data sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSBase. We assessed rate and time course of lymphocyte reconstitution after DMF discontinuation.Results
The majority of patients who developed lymphopenia while treated with DMF and subsequently discontinued treatment experienced ALC reconstitution. The median time to reach ALC ?0.8 × 109/L was 2-4 months after discontinuation for patients treated in real-world data sets; the median time to reach ALC ?0.91 × 109/L was 2 months after discontinuation in DMF clinical trials. Severity of lymphopenia on treatment and decline in ALC within the first 6 months did not affect the ALC reconstitution rate after DMF discontinuation; rather, on-treatment lymphopenia duration influenced the reconstitution rate. In patients with severe, prolonged lymphopenia for ?3 years, lymphocyte reconstitution to ?0.91 × 109/L was 12-18 months vs 2-3 months in patients with lymphopenia persisting <6 months.Conclusions
The majority of patients who discontinued DMF due to lymphopenia experienced ALC reconstitution within 2-4 months following DMF discontinuation. This may help guide clinicians in managing patients who develop lymphopenia during DMF treatment. Prolonged lymphopenia on DMF treatment is associated with slow lymphocyte recovery after DMF discontinuation.
SUBMITTER: Chan A
PROVIDER: S-EPMC7837440 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Chan Andrew A Rose John J Alvarez Enrique E Bar-Or Amit A Butzkueven Helmut H Fox Robert J RJ Gold Ralf R Gudesblatt Mark M Haartsen Jodi J Spelman Tim T Wright Katy K Ferraro Diana D Sola Patrizia P Hodgkinson Suzanne S Kalincik Tomas T Lechner-Scott Jeannette J McGuigan Christopher C Spach Karen K Chen Chongshu C Fam Sami S Wu Fan F Miller Catherine C
Neurology. Clinical practice 20201201 6
<h4>Background</h4>Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.<h4>Methods</h4>Data sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSB ...[more]