1. Impact of approaches for clinical and radiological monitoring on predicting of short-term and long-term disability outcomes in multiple sclerosis
Brian Healy, PhD
Partners MS Center
Brigham and Women’s Hospital
Harvard Medical School

2. Background
Multiple sclerosis (MS) is a complex neurologic disease with a long disease course
Providers and patients need information about both short and long term outcomes
Patients are monitored using clinical and radiological measures
Goal: Compare approaches for monitoring patients in terms of model fit at multiple time points

3. Study design/approach
CLIMB follows subjects every six months with clinical visit and annually with brain MRI scan
Clinical visits collect demographic, disability and relapse information
MRI scans are segmented to obtain brain volume and lesion volume
All occurrences with five consecutive clinical visits were identified
Models built separately in relapsing and progressive subjects
Outcome was 24 month and 84 month EDSS score
Linear mixed effects models with varying sets of predictors were compared using the AIC to identify the best number of previous EDSS and MRI measurements

4. Comparison of length of clinical follow-up
When the different observation intervals were compared, additional follow-up was more beneficial in models for 24 month EDSS measurement
24 month EDSS
84 month EDSS RR
Prog
Present EDSS
3003.3
4230.1
672.8
Present/6-month EDSS
2963.2
4226.1
674.3
Present/12-month EDSS
2925.9
4220.8
675.9
Present/24-month EDSS
2961.6
4231.3
679.3
Present/6/12-month EDSS
2924.9
4220.5
679.2
Present/12/24-month EDSS
2918.9
4223.7
682.2
All 24 month EDSS
2919.3
4227.8
690.5

5. Addition of MRI information
MRI information added to the model for the relapsing subjects and the short term follow-up in the progressive subjects
Multiple MRI measurements did not further improve model fit
24 month EDSS
84 month EDSS RR
Prog
Present EDSS
0.20
0.33
0.31
6-month EDSS
0.17
0.06
12-month EDSS
0.08
0.24
18-month EDSS
0.19
24-month EDSS
0.09
BPF
-3.03
-4.54
-6.26
-2.54
T2 lesion volume
0.01
-0.01
0.07
0.03
Age
0.005
Disease duration
0.000
-0.04

6. Conclusions
Multiple previous EDSS scores provide predictive information for short-term and long-term disability measures
The best model in terms of EDSS history depended on the outcome measure and patient group
A single MRI provides additional information, especially for 24 month measurement