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Abstract Details

Progression independent of relapses in multiple sclerosis is associated with spinal cord and brain atrophy
Multiple Sclerosis
P10 - Poster Session 10 (8:00 AM-9:00 AM)
3-011

PIRA is a major contributor of disability worsening in MS and has been extensively studied in clinical trial cohorts.

To quantify MRI predictors of disability progression and progression independent of relapse activity (PIRA) from patients with multiple sclerosis (MS) in an observational setting.

We obtained demographics, patient-reported measures (patient-determined disease steps [PDDS], relapse, and MS course), and performance measures (walking speed test [WST], manual dexterity test [MDT], and processing speed test [PST]). Inclusion criteria were at least 3 measurements and ≥6 months of follow-up. Confirmed disability worsening (CDW) was defined as a 6-month-sustained increase of ≥1 in PDDS, 20% increase for WST or MDT, or 4-point decrease for PST. Fixed and roving reference methods were applied. CDW was classified as PIRA when it occurred in the absence of relapses between the onset and confirmation of CDW (±30days). MRIs acquired within 6 months of the first visit were analyzed for whole brain fraction (WBF), T2 lesion volume (T2LV), and upper cervical spinal cord area (SCA). The baseline characteristics were compared based on CDW and PIRA status. Logistic regression was performed to predict PIRA.

4909 subjects were included. CDW occurred in 1825 (37%) using fixed baseline and in 2599 (53%) using roving baseline. PIRA represented 37% (679) of all CDW in fixed and 43% (1121) in roving. PIRA patients were older (p<0.05), had better MDT score (p<0.001), and better PST score (p<0.02). PIRA subjects had lower baseline WBF (0.803 vs 0.811, p<0.01) and SCA (74.6 vs 77.1, p<0.01) with no difference in T2LV (p>0.1). Logistic regression showed PIRA was associated with lower baseline MDT, WBF, and SCA (p<0.01).

PIRA represents a major contributor to disability accumulation in MS. Baseline brain volume and spinal cord area were associated with PIRA suggesting a potential neurodegenerative mechanism for this type of disability accrual.

Authors/Disclosures
Kunio Nakamura, PhD (Cleveland Clinic)
PRESENTER
Dr. Nakamura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INmune Bio. The institution of Dr. Nakamura has received research support from Biogen. The institution of Dr. Nakamura has received research support from PCORI. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from Novartis. The institution of Dr. Nakamura has received research support from DOD. Dr. Nakamura has received intellectual property interests from a discovery or technology relating to health care.
Scott Husak Scott Husak has nothing to disclose.
Robert A. Bermel, MD, FAAN (Cleveland Clinic) Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck Serono. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey Alan Cohen, MD (Cleveland Clinic) Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage.
Daniel Ontaneda, MD, PhD, FAAN (Cleveland Clinic) Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech/Roche. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Ontaneda has received research support from NIH. The institution of Dr. Ontaneda has received research support from PCORI. The institution of Dr. Ontaneda has received research support from NMSS. The institution of Dr. Ontaneda has received research support from Genetech.