Background

Automated and reproducible measures of MS severity and subclinical inflammatory activity and neurodegeneration in routine practice could support therapeutic decisions and accelerate research. Toward this goal, we developed and validated a software prototype, MSPie (MS PATHS Image Evaluation). MSPie runs on syngo.via Frontier (Siemens Healthcare, Erlangen, Germany) and processes standardized T2 FLAIR and T1-weighted MRIs to quantify brain parenchymal fraction (BPF), T2 lesion volume, and #new/enlarging T2 lesions (NET2L). Results are reviewable by radiologists through an interface that displays current, prior, and subtraction images, as well as overlays of brain and lesion segmentations, and allows +/- corrections of NET2L.

Objectives

To assess an image analysis prototype integrated into radiological practice to generate quantitative brain volume and lesion measurements at the point of care.

Methods

MSPie was installed at 2 MS Partners Advancing Technology and Health Solutions (MS PATHS) institutions. 3 neuroradiologists per institution used MSPie to review 40 longitudinal pairs of routine MS PATHS MRIs. For each case, radiologists performed a visual assessment of the brain segmentation used for BPF, manually corrected NET2L if needed, approved or rejected the results, and completed a performance evaluation survey.

Results

MSPie performance was assessed in 240 cases. Radiologists accepted MSPie-generated BPF and lesion results for 230/240 cases (96%). 38.8% of cases required corrections of false positive (FP) or false negative (FN) NET2L, with a mean of 2.5 (FP+FN) NET2L per case. In 94% of cases, NET2L FP+FN was £3, a prespecified design target based on radiologists’ input. MSPie detected 221/229 true NET2L, yielding a sensitivity of 96.2%. In 18% of cases, radiologists reported MSPie-detected NET2L they would have missed. Mean performance ratings on a scale of 1(poor) to 5(excellent) were: 3.9 for overall performance; 3.9 for brain segmentation; 3.9 for T2 lesion segmentation.

Conclusions

Incorporation of brain volume and T2 lesion quantification into MS imaging practice is feasible. MSPie demonstrated a high sensitivity for disease activity, detecting some NET2L that might have been missed by radiologists. MSPie achieved the prespecified target rate of acceptable false positive NET2L. MSPie might allow neuroradiologists to provide quantitative brain atrophy and T2 lesion metrics in clinical practice and to increase their diagnostic precision.

Disclosures: MS PATHS is sponsored by Biogen.

Background

Mean rates of brain atrophy in healthy controls range from 0.05-0.5%, depending on age and technical factors, including scanner, acquisition sequences, and image analysis techniques. In MS PATHS (MS Partners Advancing Technology for Health Solutions), standardized MRIs are analyzed using a software prototype (MSPie, MS PATHS Image Evaluation) that incorporates a novel approach to calculate BPF. Normative ranges measured using MSPie are needed to distinguish age- and disease-related changes.

Objectives

To establish a normative reference for interpretation of brain parenchymal fraction (BPF) in individual MS patients relative to age-matched healthy volunteers (HV).

Methods

HV aged 21-60 were recruited at 6 MS PATHS sites to be age-, race-, and gender-matched to the MS PATHS cohort. HVs were imaged at baseline and once/year using 3T scanners (Siemens Healthcare, Erlangen, Germany) and standardized acquisitions (3DFLAIR and 3DT1), as in routine MRIs in MS PATHS. MRIs from UK Biobank supplemented the normative dataset past the age of 60. All MRIs were analyzed with MSPie to calculate BPF. BPF normative percentile were calculated for each age using quantile regression. Mean annualized rate of brain atrophy was estimated from HVs with follow-up MRIs. BPF percentiles were applied to the MS PATHS cohort. Mean Processing Speed Test (PST) z-scores were compared in MS patients stratified based on BPF percentiles.

Results

209 HVs were enrolled, 590 UKBiobank HVs were selected, and 9479 MS patients had at least one MRI. HV BPF values ranged from 0.855-0.895 in the 21-30 age group to 0.796-0.882 in the 61-73 age group, demonstrating accelerating and more variable atrophy with increasing age. For MS patients age 21-73 years (n=6791), mean age-adjusted BPF percentile was 27.8%, where BPF values fell above the 50^th%-ile in 23.4% (“mild MS”) and below the 25^th%-ile in 57.6% (“severe MS”). Mean PST z-scores differed in BPF-based mild MS vs. severe MS groups (-0.15 and -0.83; p<0.001). Mean annualized BPF change in HV was -0.08% (range: -0.71% to +0.57%) based on 71 subjects (mean age: 41.1 years) with >2 MRIs.

Conclusions

Incorporating normative reference data into MSPie will aid clinicians with interpretation of individual patients’ BPF in clinical practice and may enable patient stratification based on BPF and other predictors. Additional longitudinal normative data are being collected to contextualize disease progression as measured by BPF change over time.

Disclosures: MS PATHS is sponsored by Biogen.

Background

Safety and effectiveness information for peginterferon beta-1a or intramuscular interferon (IM IFN) beta-1a in older patients (≥60 years [y]) with multiple sclerosis (MS) are limited. MS PATHS, an international network of MS centers, provides access to real-world (RW) data generated from a broad MS patient population.

Objectives

Evaluate the clinical outcomes of patients ≥60 y of age in MS PATHS treated with peginterferon beta-1a or IM IFN beta-1a.

Methods

Included patients were currently taking peginterferon beta-1a or IM IFN beta-1a or began taking either therapy at a follow-up visit, and had ≥1 follow-up clinical assessment as of November 2019. Assessments included Patient-Determined Disease Steps (PDDS), and Multiple Sclerosis Performance Test (MSPT) assessments, including Processing Speed Test (PST), Manual Dexterity Test (MDT), and Walking Speed Test (WST). Z-scores were based on normative data from 500 healthy volunteers.

Results

Analysis included 817 patients, of whom 218 (27%) were aged ≥60 y at baseline (BL). Follow-up times were similar for ≥60 y and <60 y patients (mean [SD] 1.35 [0.97] y and 1.27 [0.94] y, respectively). Older patients had higher BL PDDS score (mean [SD] 1.82 [2.14] vs 0.91 [1.48]) and higher rates of comorbidities including pain, cardiovascular, and dyslipidemia than younger patients. At BL, patients ≥60 y had significantly greater functional impairment than patients <60 y on MDT (Z-score mean [SD] -0.85 [1.79] vs -0.23 [1.56]) and WST (-1.66 [3.35] vs -0.52 [2.30]; both P<0.001), but not PST (-0.48 [1.00] vs. -0.37 [1.11]; P=0.197). Change from BL in PST, MDT or WST Z-scores at 6 months (mo), 1 y or 2 y was not significant for patients ≥60 y, whereas those <60 y showed significant improvement in PST at all 3 time points (mean change in Z-score 0.11–0.26; all P≤0.006) and in MDT at 1 and 2 y (mean change in Z-score 0.24 and 0.36; both P≤0.003). Approximately half of the ≥60-y and <60-y subgroups were relapse free at 6 mo (57% and 58%), 1 y (48% and 61%) and 2 y (49% and 60%).

Conclusions

In this RW study of patients with MS aged ≥60 or <60 y treated with peginterferon beta-1a or IM IFN beta-1a, younger patients had significantly improved PST and MDT ≥6 mo post-BL, and approximately equal proportions of patients in both age groups were relapse-free over 2 y. These results indicate that peginterferon beta-1a and IM IFN beta-1a may provide RW treatment benefits to patients with MS, including those aged 60 and above.

This study was supported by Biogen.

Background

Unemployment rates can be high among patients with multiple sclerosis (MS), and a return to work after unemployment can be difficult, highlighting the importance of treatment in preventing a departure from the workforce due to MS. Natalizumab is a highly effective treatment for patients with relapsing-remitting MS (RRMS) and was associated with positive employment outcomes in real-world studies.

Objectives

To evaluate changes in employment status in RRMS patients treated with natalizumab in the TYSABRI Observational Program (TOP), a large observational study assessing the long-term safety and effectiveness of natalizumab.

Methods

This retrospective analysis included patients aged ≤65 years at TOP enrolment (i.e., baseline [BL]) who were surveyed on their employment status in the year before natalizumab initiation and in the period since treatment initiation (N=2004). Multivariate logistic regression tested the association between BL characteristics and employment outcomes.

Results

At BL, patients had a mean (standard deviation [SD]) Expanded Disability Status Scale (EDSS) score of 3.5 (1.5). At the survey, patients had a mean (SD) of 5.5 (3.3) years of natalizumab treatment. Survey responses indicated that in the year before natalizumab initiation, 1107 patients (55.2%) were working; 814 patients (40.6%) were working full time, 53 (2.6%) were working part time due to MS, 265 (13.2%) were not working due to MS, and 240 (12.0%) and 632 (31.5%) were working part time or not at all, respectively, for other reasons. After natalizumab initiation, 861 patients (43.0%) improved (1.3%) or maintained (41.6%) their employment level, whereas 170 (8.5%) experienced a decline in employment level due to MS and 256 (12.8%) remained unemployed due to MS. Significant predictors of improving/maintaining employment status were younger age (adjusted odds ratio [aOR]: 0.756; P=0.005), lower BL EDSS score (aOR: 0.747; P<0.001), and fewer relapses in the year before natalizumab initiation (aOR: 0.829; P=0.042), but did not include sex, prior therapy use, or RRMS duration.

Conclusions

Of patients who were working prior to natalizumab initiation, 77.0% maintained or improved their employment level with an average follow up of 5.5 years. Overall, favourable outcomes were predicted by younger age and less BL disease activity, supporting the importance of natalizumab initiation early in the disease course to help prevent patients from leaving the workforce due to MS.

The TOP study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).