Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS

Chan, Andrew; 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; ... (2020). Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS. Neurology: Clinincal Practice, 10(6), pp. 510-519. American Academy of Neurology 10.1212/CPJ.0000000000000800

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Chan, Andrew Hao-Kuang

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2163-0933

Publisher:

American Academy of Neurology

Language:

English

Submitter:

Chantal Kottler

Date Deposited:

08 Jul 2020 09:08

Last Modified:

13 Dec 2020 02:47

Publisher DOI:

10.1212/CPJ.0000000000000800

BORIS DOI:

10.7892/boris.145003

URI:

https://boris.unibe.ch/id/eprint/145003

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