Biogen

Author Of 8 Presentations

Disease Modifying Therapies – Risk Management Late Breaking Abstracts

LB1252 - COVID-19 and multiple sclerosis – prevalence and the impact of disease modifying therapies (ID 2142)

Speakers
Presentation Number
LB1252
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There has been growing concern that disease modifying therapies (DMTs), as used in multiple sclerosis (MS), might increase the risk for an infection with SARS-CoV-2 and alter the clinical course of this infection.

Objectives

To assess the prevalence of COVID-19 in patients with MS (pwMS) and the potential impact of DMTs on its clinical course.

Methods

We used IBM Explorys, a data set covering electronic medical records of more than 72 million unique patients from hospitals in the United States, out of which we identified pwMS with and without PCR-confirmed COVID-19; we assessed baseline characteristics as well as DMTs for risk factors on the prevalence as well as a worse clinical outcome. Comparisons of cumulative prevalence of COVID-19, risk of hospitalization and death were made using logistic regression adjusted for patient age, sex, body mass index (BMI), comorbidities and race.

Results

We identified 30,116 pwMS with an open prescription for a DMT; 170 were COVID-19 positive. The risk of developing COVID-19 in pwMS did not appear to be higher when compared to patients with systemic lupus erythematosus (SLE), another chronic autoimmune disease (infection rate: 0.56% in MS vs. 0.58% in SLE; hospitalization: 30% vs. 36%; deaths: 3% vs 4%). PwMS with older age, male sex, high BMI, and cardiovascular disease were at higher risk to die in the context of this infection. PwMS on interferons appeared less likely to develop COVID-19 (0.35% of the overall group of pwMS) compared with high efficacy DMTs (p < .05), whereas anti-CD20 and anti-CD52 therapies were found to be associated with a higher risk of developing COVID-19 (1.67% and 1.15%) (p < .05).

Conclusions

Our findings demonstrate that MS is not prone to a higher or different risk of infection with SARS-CoV-2. Risk factors are similar to those reported for the general population. Some DMTs, however, appear to be associated with some level of protection, whereas others are associated with an increased risk for COVID-19. Such findings, once confirmed, might be taken into account when treating pwMS.

Supported by: Biogen

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Clinical Outcome Measures Poster Presentation

P0026 - Analysis of association between expanded disability status scale and patient determined disease steps (ID 421)

Speakers
Presentation Number
P0026
Presentation Topic
Clinical Outcome Measures

Abstract

Background

The Expanded Disability Status Scale (EDSS) is a commonly used measure of disability based on a clinician administered neurological exam in patients with Multiple Sclerosis (pwMS). Ordinal scores range from 0 (no disability) to 10 (death) in 0.5-point increments. The Patient Determined Disease Steps (PDDS) is a patient-reported measure of disability in pwMS, with ordinal scores ranging from 0 (no disability) to 8 (bedridden) in 1-point increments. Few studies have characterized the association between EDSS and PDDS. Those that have are limited by small sample sizes (n=96 to 103) and inconsistent and sometimes unrealistic correlations for patients with mild disability. For example, one of the studies reported a PDDS of 0 corresponds to an EDDS of 2.9.

Objectives

To characterize the association between EDSS and PDDS in a large sample of pwMS, which can help in the better application of PDDS in practice.

Methods

A total of 406 subjects participating in a US-based prospective cohort study were used for the analyses. All subjects had EDSS and PDDS assessments at baseline and approximately 12-months post-baseline, providing a total of 812 assessments. Mixed effect regression models using cubic splines, growth curve models and quadratic polynomials were employed to characterize the association between EDSS and PDDS and compared with models available in literature.

Results

The mean (standard deviation) age was 48.6 (10.35) years and 72.9% were female. Based on the Akaike’s Information Criterion, the quadratic polynomial regression was found to be the best fitting model. The equation predicting EDSS had the following form: EDSS = 1.4359 + 0.0830 * PDDS + 0.0999 * PDDS2, which was modestly convex in shape. Patients with a PDDS of zero were predicted to have an EDSS of 1.4 and patients with a PDDS of 8 were predicted to have an EDSS of 8.4.

Conclusions

The fitted relationship between EDSS and PDDS in this large sample of pwMS showed generally similar scores across the ranges of the scales. The equation predicting EDSS as a function of PDDS revealed a more realistic fit when compared against other published equations. This study successfully developed a user-friendly crosswalk between EDSS and PDDS scores, using repeat measurements over a large sample. This crosswalk can aid in the better application and interpretation of PDDS.

Sponsored by: Biogen

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Biomarkers and Bioinformatics Poster Presentation

P0057 - Decline in serum neurofilament is associated with decreased clinical and radiological disease activity over two years of dimethyl fumarate treatment (ID 1294)

Speakers
Presentation Number
P0057
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Dimethyl fumarate (DMF) treatment is associated with a decrease in serum neurofilament light chain (sNfL) in patients with relapsing-remitting multiple sclerosis (RRMS). sNfL is an exploratory biomarker of MS disease activity. Additional data describing the association between sNfL and disease activity are needed to further investigate this biomarker as a potential predictor of treatment response, which could enable a more holistic disease monitoring approach to treatment.

Objectives

To describe variation in sNfL levels with respect to clinical and radiological disease activity in DMF-treated patients.

Methods

DMF-treated patients with RRMS and complete 2Y follow-up data were analyzed. Serum samples were collected, and routine clinical and radiological assessments were conducted at baseline (BL) and at regular intervals. sNfL concentrations were measured by Single Molecule Array (SiMoA). Normative sNfL data from a cohort of 135 healthy adult controls (age range 21-82 years) were used as a comparator. Age-normative sNfL cutoffs were defined based on the 95th percentile of sNfL levels.

Results

Forty-one patients with 2Y follow-up data were included. Mean (SD) age and disease duration were 37.5 (10.1) and 6.0 (6.5) years, respectively, with mean (SD) time on DMF treatment 43.8 (9.15) months. Twenty-nine (70.7%) patients were treated with a previous MS therapy. Nineteen (46.3%) and 22 (53.7%) patients were below and above age-normative sNfL level at BL, respectively. Over 2Y, mean (95% CI) sNfL level decreased from 8.5 (7.1, 10.2) to 3.4 (2.0, 4.0) pg/ml, representing a 36.6% annual decrease, and 60% decrease over 2Y. Patients experienced a 71.1% (95% CI: 38.8%, 86.3%) reduction in ARR from 1Y prior to BL (0.463, 95% CI [0.279, 0.724]) to 2Y (0.134 [0.067, 0.24]), and 75.6% (59.4%, 87.1%) patients were free of new T2 lesions at 2Y. sNfL was below age-normative level in 53.7% (37.6%, 69%) of patients at BL vs 97.6% (85.6%, 99.9%) at 2Y. Patients with sNfL below age-normative level at BL generally remained below this threshold. At 2Y, patients both above and below age-normative sNfL level at BL experienced low cumulative ARR (95% CI) of 0.132 (0.043, 0.307) and 0.136 (0.05, 0.297), respectively, representing reductions of 75% and 66.7%.

Conclusions

DMF-treated patients reached NfL levels approaching that of healthy controls over 2Y with a reduction in disease activity, regardless of sNfL level at BL in this real-world setting. These data support a correlation between reductions in sNfL levels and decreased disease activity over 2Y of treatment, and potential of sNfL as a biomarker of treatment response that could be assessed during treatment in addition to standard of care monitoring.

Supported by: Biogen.

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Clinical Outcome Measures Poster Presentation

P0060 - Descriptive study on recruitment effort for a remote monitoring study in Multiple Sclerosis: RADAR study (ID 1529)

Abstract

Background

There is a growing body of literature highlighting the role that wearable and mobile remote monitoring technology (RMT) can play in the assessment of Multiple Sclerosis (MS) and how it could improve clinical care and improve efficiency of research.

The Remote Assessment of Disease and Relapse in the Central Nervous System (RADAR-CNS) study is a pan-European consortium aimed to improve the management of different CNS disorders such as MS, Epilepsy or Major Depression using smartphones and wearable devices.

Most of the available data are based in small monocentric studies, however the full validation of these digital devices requires multicenter, well designed studies providing information on feasibility and acceptability.

Objectives

We aimed to describe the outcomes of the recruitment process in the Multiple Sclerosis (MS) RADAR-CNS disability and fatigue study (D&F).

Methods

The study was run in three European centers. Main eligibility criteria for D&F study were patients with relapsing-reminting or secondary progressive MS with an EDSS score between 2.0 and 6.0. Passive and active data were continuously collected through wearables (FitBit) and mobile phones (Android) and compared to the on-site visit every 3 months. The study duration is 2 years. The study sample size was 400 patients.

Results

The enrolment of the D&F study extended for a period of 18 months. We identified 4094 potential candidates (min-max 885-1789). At the end of the recruitment period, 678 (16.6%; min-max 0-24.2%) remained in the pre-screening phase. 3416 (min-max 885-1454) patients were assessed for eligibility. Out of those, 2372 (69.4%; min-max 53.3-87.1%) were excluded for not fulfilling the eligibility criteria: 1520 (64.1%; 15.0-87.1%) did not meet the EDSS score, 254 (10.7%; 0.2-49.6%) would not be suitable in the investigators opinion and 598 (25.2%; 3.0-60.3) did not have an Android. Out of the 1044 (30.6%; 12.9-46.7) eligible candidates, 644 (61.7%; 13.8-79.7%) declined to participate. A total of 400 (90-162) patients, 9.8% of the potential candidates, were enrolled into the study.

Conclusions

Our study illustrates the primary challenges in recruiting MS patients in RMT studies related to eligibility, both clinical and technological criteria, followed by reasons related to patients preferences. There is variability in the recruitment approach between centers. In future studies, developing technology for all types of phones and more attractive assessment for patients should be considered.

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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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Biomarkers and Bioinformatics Poster Presentation

P0157 - Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis (RRMS) patients in the CombiRx trial (ID 798)

Speakers
Presentation Number
P0157
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Serum neurofilament light-chain (sNfL) is associated with disease activity and tissue damage, predicts long-term outcomes, and is reduced by disease-modifying therapies in RRMS patients.

Objectives

In a post hoc analysis, determine sNfL differences from baseline (BL) to 48 months and associations with long-term clinical outcomes in patients treated with intramuscular (IM) interferon (IFN) beta-1a, glatiramer acetate (GA), or both therapies (IFN+GA).

Methods

CombiRx was a placebo (PLB)-controlled double-blind phase 3 trial in treatment-naive RRMS patients randomized to IM IFN beta-1a 30 µg weekly+PLB, GA 20 mg/mL daily+PLB, or IFN+GA treatment for up to 7 years. Samples for biomarker analysis were collected at BL, 6, 12, 36, and 48 months from volunteers for a substudy offered in most sites. Relapses and Expanded Disability Status Scale (EDSS) scores were collected every 3 months. A Simoa Human Neurology 4-Plex A assay analysed sNfL levels. A linear mixed model compared sNfL values over time adjusted for BL EDSS, age, sex and body mass index (BMI). A Cox regression model with the same covariates analysed BL sNfL as a predictor of relapse.

Results

Samples were collected from 159 IFN, 172 GA, and 344 IFN+GA patients. BL characteristics were generally well balanced, including mean age, sex, mean BMI, mean time since symptom and diagnosis onset, and mean EDSS scores. Significant reductions relative to BL in sNfL levels were seen at 6, 12 and 36 months in the IFN, GA, and IFN+GA treatment groups. BL sNfL ≥16 pg/mL significantly predicted relapse within 90 days (hazard ratio [HR]: 2.25, P=0.0041), 180 days (HR: 1.67, P=0.0130) and 1 year from BL (HR: 1.40, P=0.0435), but not over the entire study duration (HR: 1.08, P=0.5596). In patients with BL sNfL ≥16 pg/mL and ≥1 BL gadolinium-enhancing (Gd+) lesion, a significantly higher percentage (16.8%) relapsed within 90 days than in patients with BL sNfL ≥16 pg/mL and no BL Gd+ lesions (9.2%), or BL sNfL <16 pg/mL with (7.3%) or without BL Gd+ lesions (6.7%) (P=0.0051).

Conclusions

Treatment with IFN, GA, and IFN+GA significantly reduced sNfL levels within 6 months and was maintained over 36 months. Results suggest that BL sNfL levels predict relapses within 1 year, and that the combination of lesion activity and sNfL is a stronger predictor of relapse than either one alone.

This analysis was funded by Biogen. Biogen also funded the writing support for this abstract, which was provided by Ashfield Healthcare Communications (Middletown, CT, USA).

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1036 - Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: results from MS PATHS (ID 1794)

Speakers
Presentation Number
P1036
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Understanding patient-reported changes in physical, mental, and social health after starting MS therapy is important in optimizing treatment.

Objectives

Assess changes in the Quality of Life in Neurological Disorders (Neuro-QoL; NQ) questionnaire after starting natalizumab (NAT) and compare to another high efficacy therapy - ocrelizumab (OCR).

Methods

T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. NQ scores from visits post NAT initiation were compared to last previous NQ (baseline, BL) to calculate the annualized rate of change and the likelihood of clinically meaningful change (≥5-point) in the overall cohort and in patients with abnormal BL NQ (T-score worse than 50; 36%-76% of the population). Subgroup analyses in NAT- and OCR-treated patients were conducted with multivariate mixed-effects regression models after propensity score weighting and adjustment for antidepressants, year and drug*year interaction.

Results

164 NAT patients were analyzed; mean (SD) follow-up was 6 (6) months and number of assessments was 2.3 (1.6). Significant improvements from pre-NAT BL were seen in 8 of 12 NQ domains. Patients with BL impairment had significant improvements in 10 NQ domains and higher rates of improvement compared to the overall cohort (p<0.05). In this subgroup, the largest number of patients with ≥5-point improvement was seen for positive affect and well-being (PAF) (43%), emotional and behavioral dyscontrol (EBD) (38%) and sleep disturbances (35%). In the subgroup of NAT (n=145)- and OCR (n=520)-treated patients, the annualized improvement rates were higher with NAT than with OCR, reaching statistical significance for PAF (p=0.02), sleep disturbances (p=0.003), and satisfaction with social roles and activities (SRA) (p=0.03). In patients with impaired BL NQ, significantly higher rates of improvement were seen with NAT than with OCR for EBD (p=0.01), participation in SRA (p=0.0001) and satisfaction with SRA (p=0.02). The percentage of patients with ≥5-point improvement was numerically higher with NAT than OCR for 9 of 12 NQ domains; differences in the likelihood of ≥5-point improvement were not significant.

Conclusions

NAT can lead to clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias as their magnitude exceeded improvements with another high-efficacy therapy (OCR).

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