TY - JOUR
T1 - Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS
AU - Chan, Andrew
AU - Rose, John
AU - Alvarez, Enrique
AU - Bar-Or, Amit
AU - Butzkueven, Helmut
AU - Fox, Robert J.
AU - Gold, Ralf
AU - Gudesblatt, Mark
AU - Haartsen, Jodi
AU - Spelman, Tim
AU - Wright, Katy
AU - Ferraro, Diana
AU - Sola, Patrizia
AU - Hodgkinson, Suzanne
AU - Kalincik, Tomas
AU - Lechner-Scott, Jeannette
AU - McGuigan, Christopher
AU - Spach, Karen
AU - Chen, Chongshu
AU - Fam, Sami
AU - Wu, Fan
AU - Miller, Catherine
N1 - Funding Information:
The Article Processing Charge was funded by Biogen.
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - BackgroundDelayed-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.MethodsData 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.ResultsThe 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.ConclusionsThe 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.
AB - BackgroundDelayed-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.MethodsData 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.ResultsThe 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.ConclusionsThe 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.
UR - http://www.scopus.com/inward/record.url?scp=85148084740&partnerID=8YFLogxK
U2 - 10.1212/CPJ.0000000000000800
DO - 10.1212/CPJ.0000000000000800
M3 - Article
C2 - 33510947
AN - SCOPUS:85148084740
SN - 2163-0402
VL - 10
SP - 510
EP - 519
JO - Neurology: Clinical Practice
JF - Neurology: Clinical Practice
IS - 6
ER -