Abstract Details

Title Predicting MRI Changes in Patients with MS in the Absence of Acute Inflammation

Topic Multiple Sclerosis

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-010

Objective To predict changes in MRI variables of interest occurring in absence of acute inflammation (AAI), defined as periods with no relapses nor new enlarging T2 lesions.

Background Treatments targeting MS disease processes in AAI are lacking, mainly due to the lack of MRI biomarker endpoints suitable for short-term trials.

Design/Methods

Patients in MS PATHS with ≥2 standardized MRIs over ≥180 days without change in treatment and AAI over follow-up were included. Data were split into training (70%) and testing (30%) sets. Regression models for annualized changes in brain parenchymal fraction (BPF), T1 lesion volume (T1LV), and T1 lesion volume as a proportion of chronic T2 lesion volume (T1LP) were generated in the training set using baseline Patient Determined Disease Steps, prior treatments, treatment group, prior relapse rate, BPF, T1LV, T1LP, cortical and total gray matter and thalamic volume fractions, T2 lesion volume (T2LV), mean normalized T1 intensity within chronic T2 lesions, and spinal cord cross-sectional area (SCCA) as covariates. Model performance was evaluated in the test set via R-squared between predicted and actual change.

Results N=1078 patients with mean MRI follow-up of 1.4 years. There were no significant predictors of change in BPF and T1LP (R-squared <0). R-squared and adjusted R-squared for change in T1LV models on the test set were 0.18 and 0.16, respectively; significant covariates were sex (male; P<0.001), T1LV (P<0.001), T2LV (P<0.001), thalamic fraction (P<0.05), and SCCA (P<0.05).

Conclusions Baseline demographics, clinical characteristics, and MRI markers did not predict changes in proposed MRI measures of progression in AAI, with the exception of a small proportion of the variance in T1LV change. This finding highlights the need to better understand the processes driving disease progression in AAI. Ability to reliably predict subsequent changes in MRI measures might enable population enrichment in future drug trials targeting disease progression in AAI.

Authors/Disclosures
Nolan Campbell PRESENTER	Nolan Campbell has received personal compensation for serving as an employee of Biogen. Nolan Campbell has stock in Biogen.
	No disclosure on file
	No disclosure on file
Daniel P. Bradley	Daniel Bradley has nothing to disclose.
Cynthia Grossman	Cynthia Grossman has received personal compensation for serving as an employee of Biogen. Cynthia Grossman has stock in Biogen .
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban 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. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Alex Rovira	Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofy. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Alex Rovira has stock in Tensor Medical.
Mar Tintoré, MD, PhD	The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche . The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme . The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela bio. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. The institution of Mar Tintoré, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parexel and UCB Biopharma. Mar Tintoré, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal: Experimental, Translational and Clinical. The institution of Mar Tintoré, MD, PhD has received research support from Fundació La Marató de TV3. The institution of Mar Tintoré, MD, PhD has received research support from Instituto de Salud Carlos III. The institution of Mar Tintoré, MD, PhD has received research support from Instituto de Salud Carlos III. The institution of Mar Tintoré, MD, PhD has received research support from Instituto de Salud Carlos III.
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.

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