Lifetime cumulative DMT exposure is associated with a slower rate of brain atrophy
Author(s): ,
C. Azevedo
Neurology, University of Southern California, Los Angeles
S. Cen
Neurology, University of Southern California, Los Angeles
A. Jaberzedeh
Neurology, University of Southern California, Los Angeles
S. Hauser
Neurology, University of California San Francisco, San Francisco, CA, United States
D. Pelletier
Neurology, University of Southern California, Los Angeles
ECTRIMS Online Library. Azevedo C.
Oct 12, 2018; 229028
Christina Azevedo
Christina Azevedo
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Abstract: P1188

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Background: The effect of DMT on brain atrophy has mostly been reported from RCTs and extension phases, where the duration of on-study DMT exposure is fixed and the effect is measured at the group level. In a unique dataset from a large observational study where all pre-study and on-study DMT exposure (i.e. lifetime cumulative DMT exposure; LC-DMT) was recorded for each patient, we examine the effect of LC-DMT on brain atrophy at the individual level.
Aim: To test the hypothesis that an individual's rate of brain atrophy diminishes as LC-DMT exposure increases over time.
Methods: 520 relapsing MS subjects were followed in a single-center prospective cohort between 2005-2010 with annual standardized 3T MRIs and clinic visits. Subjects could be treated with DMT according to clinician judgment (mainly injectables given study period). 1mm3-3DT1s were processed longitudinally with FreeSurfer v5.3 and SIENA. LC-DMT was calculated at each MRI time point and modeled as a time-varying covariate. Percent change from baseline whole brain (SIENA), grey matter (total, cortical, and subcortical), thalamic, and white matter volumes were estimated in mixed effects models with LC-DMT as the primary exposure and age, disease duration, sex, baseline lesion volume, and new T2 lesions over time as covariates.
Results: After excluding 115 subjects never exposed to DMT, 405 subjects (1912 MRIs) were analyzed (age 41.9±9.6 yrs, disease duration 9.0±8.1 yrs, 68.4% female). Mean DMT exposure was 5.2±3.3 yrs (range 0.03-16.4). In each brain region, after adjusting for covariates, the rate of atrophy within an individual slowed significantly with each year of additional LC-DMT exposure. For SIENA, each additional year of LC-DMT was associated with an attenuation of 0.017±0.005% (p< 0.01) in the rate of atrophy (e.g. -1.475%/y with 1 year LC-DMT, -1.458%/y with 2 yrs, -1.44%/y with 3 yrs, etc.). Similar attenuations were seen in total grey matter (0.060±0.007%; p< 0.01), cortical grey matter (0.054±0.006%; p< 0.01), subcortical grey matter (0.014±0.007%; p=0.04), thalamic (0.056±0.009%; p< 0.01), and white matter volumes (0.043±0.006%; p< 0.01).
Conclusion: These novel findings report the effect of lifetime cumulative DMT exposure on brain atrophy at the individual level. These results suggest that brain atrophy may continue to slow with each additional year of treatment with DMT, and that the longer a patient stays on DMT, the more they may benefit with respect to brain atrophy.
Disclosure: Dr. Azevedo has received consulting fees from Guerbet, Genentech, Biogen, and Sanofi Genzyme. Drs. Cen and Jaberzedeh have no disclosures to report. Dr. Hauser has served on scientific Advisory Boards for Annexon, Symbiotix, Bionure, and Molecular Stethoscope. He is on the Board of Trustees for Neurona Therapeutics. Dr. Hauser has also received travel reimbursement and writing assistance from F. Hoffman-La Roche Ltd. for CD20-related meetings and presentations. Dr. Pelletier has received consulting and/or speaking fees from Novartis, Roche, Sanofi Genzyme, and Vertex. Funding: NIH National Institute of Neurological Disorders and Stroke (R01NS062885 to D.P.) for MRI data acquisition and processing, Biogen and Glaxo-Smith-Klein for MRI data acquisition, and NIH National Center for Advancing Translational Science (UL1TR001855) through an Institutional Career Development Award to C.J.A.

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