Abstract Details

Title Longitudinal Measures of Radiographic Outcomes as Predictors of Clinical Disability in Multiple Sclerosis: A 12-Year Study

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-001

Objective To examine the ability of conventional and advanced imaging to predict long-term neurological function.

Background More accurate imaging predictors of long-term disability are needed in multiple sclerosis(MS).

Design/Methods Data was collected from an existing 12-year observational cohort. MRI measures ((parenchymal fraction(BPF), cumulative gad-enhancing lesions(GdE), T1 and T2 lesion volumes(T1LV, T2LV), and whole brain magnetization transfer ratio(WBMTR)) from baseline, months 6, 12, and 48 were calculated using previously validated methods. Multivariate regression modeled MRI effects on year 12 MS functional composite(MSFC). Optimal cutoff points were determined via Youden index and were used in Cox regression modeling of MRI effects on disability-progression-free survival based on expanded disability status scale(EDSS).

Results

66 patients with ≥1 follow-up MRIs were analyzed. Baseline characteristics included: 53% relapsing-remitting MS, mean age 42.4±9.18 years, 69% female, mean symptom duration 9.22±8.46 years, mean T1LV 4.12±6.48ml, mean T2LV 25.7±23.7ml, mean BPF 0.84±0.03, mean WBMTR 35.17±1.4, median MSFC 0.307, median EDSS 2.0. Month 6, 12, 48 MRI metrics explained 50.1%, 50.2%, 22.3% of the variance in year 12 MSFC change, respectively. The strongest predictors of year 12 MSFC change were BPF change from baseline to month 12(β: -1.67, p: 0.005) and to month 6(β: -1.52, p: 0.026). The identified cutoff of 0.37% BPF change in the first year however did not affect progression-free survival(HR: 1.89, p=0.14). T2LV change at month 12 predicted year 12 MSFC change(β: 0.09, p: 0.025). Identified cutoff of 8.28% T2LV change in the first year predicted progression-free survival(HR: 3.065, p: 0.023). Changes in GdE, T1LV, and WBMTR at months 6 and 12 did not have significant predictive effects on MSFC/EDSS worsening. Measures at month 48 were not predictive of MSFC/EDSS worsening after accounting for month 12 values.

Conclusions Early changes in BPF and T2LV were the strongest predictors of long-term clinical performance, suggestive of the combined effects of neurodegeneration and demyelination.

Authors/Disclosures
Jenny J. Feng, MD (Ochsner Clinic) PRESENTER	Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon.
Kunio Nakamura, PhD (Cleveland Clinic)	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.
Richard A. Rudick, MD, FAAN (Optimal Brain Health Consultants)	Dr. Rudick has received personal compensation for serving as an employee of Biogen. Dr. Rudick has received stock or an ownership interest from Biogen. Dr. Rudick has received publishing royalties from a publication relating to health care.
Jeffrey A. 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 Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. 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 Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.
Elizabeth Fisher	Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has stock in Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care.
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 as a Consultant for BMS. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. 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.

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