Determination of early prognostic factors associated with 10-year outcome in multiple sclerosis: a comprehensive single centre study (2271)

Objective: To derive early demographic, clinical, radiographic, and laboratory factors that predict the 10-year outcome of patients with multiple sclerosis (MS). Background: The course of MS is variable: some endure many attacks and accrue irreversible disability; others sustain milder disease. Certain prognostic factors confer greater risk, but to an unknown extent, and high-efficacy treatment (HET) reduces disease activity but has side effect risks. Thus, early prediction of disease course may allow for personalized MS treatment. Design/Methods: We reviewed patients enrolled in the Comprehensive Longitudinal Investigation of MS at Brigham and Women’s Hospital (CLIMB) with 10-year follow-up. Thirty-five predictor variables were collected: baseline demographics and comorbidities, and early, defined as within 3 years from symptom onset, clinical, radiographic, and serum biomarker data, including neurofilament light-chain levels (NFL). Outcome variables, defined from year 3 to 10 post-symptom onset, included escalation to HET, new attacks or MRI activity, expanded disability status scale (EDSS), and brain atrophy. Multiple logistic and linear regression analysis was performed. Results: Complete data was available for 122 patients. Fifty-two (43%) escalated to HET and 86 (70.5%) had new attacks, both associated with younger age (p=0.001 and p=0.009, respectively). MRI activity in 99 (81%) was associated with higher BMI (p=0.006), vascular comorbidities (p=0.006), NFL (p=0.027), and early MRI activity (p=0.015). Forty patients (33%) had EDSS worsening, associated with injectables as first treatment (p=0.018) and less likely in patients with monofocal sensory attacks (p=0.026). Brain atrophy was associated with neurologic comorbidities (p=0.005) and NFL (p=0.008). Conclusions: Different clinical, radiographic, and serum biomarkers are associated with 10-year outcome measures in MS. A prognostic score to stratify patients for treatment decisions must be encompassing and prospectively validated. This study was funded in part by a Postdoctoral Fellowship grant from the Multiple Sclerosis Society of Canada to GB and by the U.S. Department of Defense (W81XWH-18-1-0648) to TC. Disclosure: The institution of Dr. Bose has received research support from Multiple Sclerosis Society of Canada. Mr. Lokhande has nothing to disclose. The institution of Dr. Sotiropoulos has received research support from Mallinckrodt. The institution of Dr. Sotiropoulos has received research support from United States Department of Defense. Mariann Polgar-Turcsanyi has nothing to disclose. The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme. Shristi Saxena has nothing to disclose. Fermisk Saleh has nothing to disclose. The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has received stock or an ownership interest from vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc.. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave.