Biogen

Author Of 4 Presentations

Clinical Outcome Measures Poster Presentation

P0062 - Developing standard data of cognitive function using Processing Speed Test in Japanese healthy volunteers and comparison to the US normative data (ID 1616)

Speakers
Presentation Number
P0062
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Cognitive dysfunction can be observed early in the disease course of multiple sclerosis (MS) patients and has important consequences for daily activities. International guidelines recommend annual screening with the Symbol Digit Modalities Test (SDMT) and use of electronic administration to increase clinical adoption. The Processing Speed Test (PST) is a self-administered, iPad®-based validated adaptation of the SDMT in MS. The PST is not yet widely used in Japan, and there are few reports of its usage in Japanese subjects.

Objectives

To develop normative data of the PST score on Japanese healthy volunteers (HVs) in order to utilize it as a cognitive function test on Japanese patients with MS, and to characterize the PST score distribution between Japanese HVs and United States (US) HVs.

Methods

A single arm, cross-sectional study was conducted in Japanese HVs. The primary endpoint was the distribution of PST score. The secondary endpoints were distribution of PST scores stratified by age, educational status, and gender. Comparison of the PST scores between Japanese and US HVs collected in a previously reported study was evaluated using an age, gender, and education matched analysis.

Results

Of 254 subjects who participated in this study, 242 subjects with a Mini Mental State Examination score ≥ 27 were analyzed. The mean age was 44.1 years, 51.2% were male and 60.7% were educated over 13 years (vocational school, university, or more educated). Mean PST score (±SD) was 61.8±10.0, median of 62.0 (min 37, max 88). The mean PST score (±SD) significantly decreased with age, with scores of 69.6±8.8 (20-29 years, n=52), 64.9±10.9 (30-39 years, n=45), 63.5±6.1 (40-49 years, n=46), 57.1±8.7 (50-59 years, n=44) and 54.3±6.7 (60-65 years, n=55). The mean score (±SD) with education over 13 years (63.9±9.8) was significantly higher than with education 12 years or less (58.7±9.7) (p<0.0001). There was no significant difference in PST score between males (61.6±10.9) and females (62.0±9.1) (p=0.75). Mean (95% CI) difference between Japanese and US HV PST scores from the matched analysis was 10.2 (8.2, 12.2) (p<.0001), with Japanese > US.

Conclusions

The PST score in healthy Japanese subjects significantly decreased with age and was significantly higher in subjects with higher educational background. The average PST score was higher in Japanese HVs compared to US HVs. Use of country specific normative data may contribute to more accurate cognitive screening in Japanese MS patients.

Study supported by: Biogen

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Clinical Outcome Measures Poster Presentation

P0142 - Real-world effectiveness of dimethyl fumarate versus fingolimod using novel outcomes in a heterogeneous patient cohort (ID 708)

Speakers
Presentation Number
P0142
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Prior studies suggested comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapses and traditional MRI metrics. We expanded on these assessments with new outcomes, while also accounting for comorbidities.

Objectives

Compare the real-world effectiveness of DMF vs. FTY with standardized neuroperformance, MRI, and biomarker (serum neurofilament light [sNfL]) measures.

Methods

Patients were eligible if on DMF or FTY at enrollment in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network with ≥1 year of follow up and ≥1 MRI in the previous year. Sensitivity analysis included a sub-group of patients who initiated DMF or FTY within 2 years prior to MS PATHS. Propensity score weighting model covariates included demographics, MS disease history parameters, clinical and radiographic characteristics, cardiovascular disease, and diabetes. Generalized estimating equation (GEE) models assessed the differences in means and in 1-year change in neuroperformance and MRI outcomes. Logistic regression models compared sNfL with age-adjusted normative thresholds.

Results

644 DMF and 564 FTY patients had neuroperformance data, 194-354 DMF and 201-385 FTY patients had MRI assessments, 152 DMF and 118 FTY patients had NfL samples. The number of follow-up assessments was comparable between groups (approximately 2 clinical, 2 MRI, and 1 biomarker). Mean time (SD) since treatment initiation was 2.2 (1.5) years for DMF and 2.6 (2.1) years for FTY. No differences were observed in the means or slopes of change for any of the analyzed outcomes. Differences in slopes of change were minimal for processing speed (0.06, p=0.8), manual dexterity (-0.1, p=0.5), walking speed (-0.03, p=0.7), contrast sensitivity (-0.03, p=0.9), patient-determined disease steps (0.02, p=0.5), relapses (0.001, p=0.9), brain parenchymal fraction (0.0003, p=0.3), new T2 lesions (0.3, p=0.1), Gd+ lesions (0.1, p=0.1), and grey matter fraction (0.002, p=0.2). There was no difference in the proportion of patients with elevated sNfL (p=0.12). The sub-group consisted of 123 DMF and 130 FTY patients with mean time (SD) since treatment initiation of 10.2 (6.9) and 10.9 (7.2) months, respectively. Subgroup sensitivity analyses showed similar findings.

Conclusions

DMF and FTY demonstrated similar effectiveness on standardized quantitative neuroperformance, MRI, and biomarker outcomes in a heterogeneous, real-world cohort.

Supported by: Biogen

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Imaging Poster Presentation

P0592 - In-clinic performance of MSPie, an image analysis prototype for automated MRI quantitative point-of-care metrics in MS (ID 1310)

Abstract

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.

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Imaging Poster Presentation

P0594 - Interpreting brain parenchymal fraction by comparison to healthy volunteers: Initial results from the MS PATHS normative sub-study (ID 1646)

Abstract

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 50th%-ile in 23.4% (“mild MS”) and below the 25th%-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.

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