Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS
Publisher DOI
PubMed ID
33510947
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, butlymphocyte
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, ontreatment 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.
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, butlymphocyte
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, ontreatment 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.
Date Issued
2020-01-02
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Rose, John | |
Alvarez, Enrique | |
Bar-Or, Amit | |
Butzkueven, Helmut | |
Fox, Robert J. | |
Gold, Ralf | |
Gudesblatt, Mark | |
Haartsen, Jodi | |
Spelman, Tim | |
Wright, Katy | |
Ferraro, Diana | |
Sola, Patrizia | |
Hodgkinson, Suzanne | |
Kalincik, Tomas | |
Lechner-Scott, Jeannette | |
McGuigan, Christopher | |
Spach, Karen | |
Chongshu, Chen | |
Fam, Sami | |
Wu, Fan | |
Miller, Catherine |
Additional Credits
Journal
Neurology: Clinincal Practice
Publisher
American Academy of Neurology
ISSN
2163-0933
Access(Rights)
open.access