Author Of 3 Presentations
P0067 - Disability improvement by Multiple Sclerosis Functional Composite in progressive MS patients and MRI features (ID 1729)
Abstract
Background
Disability improvement is an important functional measure in progressive MS. The MRI features of disability improvement have not been explored.
Objectives
To assess quantitative brain and spinal cord MRI measures, including volumetric features, that correlate with improvement in the T25FW or 9HPT compared to multiple sclerosis (MS) patients with stable or worsening features.
Methods
A nested cohort from the SysteMS substudy of Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) Study was selected to match inclusion criteria for patients enrolling in a phase 2 trial of repeat dose intrathecal Mesenchymal Stem Cells-Neurotrophic Factor (MSC-NTF) cells in patients with progressive MS (NCT03799718). 3T MRIs at baseline and at follow-up timepoint (12-24 months later) underwent brain and lesion volumetric analysis by Icometrix, as well as mean upper cervical cord area (MUCCA) which generated 34 measures. These 34 MRI volumetric measures (ml) were compared in patients with improved versus patients with worsening or stable 9-hole peg test (9HPT) or timed-25-foot-walk (T25FW) scores. Results were not corrected for multiple comparisons due to the exploratory nature of this study.
Results
48 patients met inclusion criteria. 17 patients had improved 9HPT score, while 29 had worsened or had stable 9HPT score from baseline to 12-24 months later. Whole brain volume at baseline for these 3 cohorts (Improved 9HPT:1505±51 vs. stable-worse 9HPT:1471±62;p=0.069;t-test) and follow-up (Improved:1501.555±52.039 vs. stable-worse:1461.304±63.562);p=0.03;t-test) differed between the two groups, as did gray matter volume at follow-up (Improved 1505.059 ±50.961 vs. stable-worse 865.57±41.352); p=0.063:t-test). For T25FW, 18 patients had an improved score, while 27 were worsened or stable over the 12-month period. Deep white matter FLAIR/T2 lesion volume at baseline (Improved:0.43±0.507 vs. stable-worse:0.827±0.561;p=0.03;t-test) and follow-up (Improved:0.429±0.503 vs. stable-worse:0.864±0.603;p=0.02) differed between two T25FW groups. MUCCA was not associated with improvement measures.
Conclusions
Improved 9HPT measures over a 12-month period correlated with baseline brain volume, while T25FW improvements correlated with baseline deep white matter T2 lesion volume. These results will inform analysis of clinical outcomes in the ongoing phase 2 clinical trial of MSC-NTF cells in progressive MS.
P0488 - Relapse recovery in MS: Effect of treatment and contribution to long-term disability (ID 1039)
Abstract
Background
Although a small number of studies has shown that recovery from relapses in multiple sclerosis appears to contribute to long-term outcomes, relapse recovery has largely been ignored as a treatment endpoint and predictor of disability. We hypothesized that relapse recovery in the early stages of disease will impact longer term disability.
Objectives
The first aim of this study was to identify demographic and clinical predictors associated with incomplete recovery from relapses in the first 3 years from the first MS symptom. The second aim was to examine the relationship between incomplete recovery in first 3 years and 10-year disability outcomes.
Methods
Recovery from relapses in the first three years from the first symptom was retrospectively assessed in 360 patients with relapsing remitting multiple sclerosis enrolled in the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB study), a large longitudinal cohort. Complete or incomplete recovery from each relapse was determined based on the return of the Expanded Disability Status Scale (EDSS), Functional System Scale (FSS) and neurologic signs to baseline levels at least 6 months after symptom onset. Univariate and multivariable models were used to associate recovery with demographic and clinical factors and to predict 10-year disability and MRI outcomes (brain parenchymal fraction and T2 lesion volume).
Results
Including their initial episode, the 360 included patients had a total of 736 relapses within the first three years from their first symptom. 44.6% of these relapses had an incomplete recovery at 6 months. Relapses in untreated patients had an incomplete recovery in 51.8% of cases, compared to 28.9% in patients who were being treated with a disease modifying drug (p<0.001). In the multivariable analysis, recovery from relapses in the first 3 years was better younger patients, who were on interferon treatment, had no bowel or bladder symptoms and had a longer interval since their first symptom. For every incomplete recovery in the first three years, the EDSS at 10 years increased by 0.6 points, and the timed 25-foot walk at 10 years increased by 0.5 seconds. Both disability outcomes were also higher with older age at first symptom and higher BMI. Brain atrophy, measured by the brain parenchymal fraction on MRI, was associated only with older age at first symptom, whereas T2-hyperintense lesion volume was only associated with smoking.
Conclusions
Early initiation of first-line disease-modifying treatments can improve relapse recovery, which in turn prevents long-term disability.
P1010 - Comparison of Models for Disability Accumulation on the Expanded Disability Status Scale in Multiple Sclerosis (ID 1665)
Abstract
Background
When assessing long-term trends in disability accumulation and economic models to compare treatments in multiple sclerosis (MS), disability accumulation on the Expanded Disability Status Scale (EDSS) is commonly assumed to depend only on the present state of the patient. Such models also often assume that the probability of disability accumulation is constant over the disease course.
Objectives
The objective of this study was to assess the assumptions of models used to describe disability accumulation within patients with MS.
Methods
Patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) who had ≥6 consecutive clinic visits, which occurred every 6 months, were included in this analysis. This yielded 7257 observations for 1039 patients. To assess whether a previous EDSS score only was sufficient for modeling disability accumulation, we compared 2 models for EDSS transitions with the EDSS scale grouped into 3 score levels (0–1.5, 2–3.5, ≥4) using a likelihood ratio test. The first transition model included only the present EDSS score, and the second model included the present and the previous EDSS scores. In addition, we fit a repeated measures proportional odds model with 1, 2, and 3 previous EDSS scores to assess if additional previous EDSS scores added to the model. To determine if the probability of disability accumulation changed with time, we assessed whether disease duration <15 years or ≥15 years was associated with a change in the transition matrix using a likelihood ratio test. Finally, we fit the repeated measures proportional odds model to assess if disease duration improved the model that included 3 previous EDSS scores.
Results
When the model with only the present EDSS score was compared with the model with 2 previous EDSS scores, the model including the 2 previous EDSS scores led to a better model fit (P<0.001). Further, all previous EDSS scores were associated with subsequent EDSS score in the repeated measures proportional odds model (1 previous EDSS, OR [95% CI]: 4.64 [4.31–4.99]; 2 previous EDSS, OR [95% CI]: 1.77 [1.65–1.90]; 3 previous EDSS, OR [95% CI]: 1.63 [1.53–1.73]). Incorporating disease duration also improved model fit using both approaches (P<0.001 for each method).
Conclusions
Additional EDSS history and disease duration may be important to incorporate into disability accumulation modeling for MS.