Biogen

Author Of 7 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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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

P0120 - Neuroperformance test outcomes as predictors of employment in a large, heterogeneous real world MS populations: Results from MS PATHS (ID 1758)

Speakers
Presentation Number
P0120
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Neuro-performance testing has been used extensively in MS clinical trials, resulting in a large literature on processing speed (Symbol Digit Modalities Test [SDMT]), manual dexterity (9-Hole Peg Test [9HPT]), and walking speed (25-foot walk [25FW]). Computer adapted versions were developed and validated, to support widespread use in clinical practice. The Multiple Sclerosis Performance Test (MSPT) includes a self-administered Processing Speed Test (PST), simulating SDMT; Manual Dexterity Test (MDT), simulating 9HPT; and Walking Speed Test (WST), simulating 25FW. MSPT is deployed within the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network. Optimal test thresholds associated with employment status in a real-world population have not been reported.

Objectives

To determine thresholds for standardized test scores of processing speed, manual dexterity, and walking speed as predictors of employment status in a real world MS population.

Methods

Neuroperformance testing was done as part of clinical visits in MS PATHS. Employment status was collected via standardized questionnaire. Patients aged 18 to 60 in the US were divided into a training set (n=3210) and a test set (n=1605). PST, MDT and WST benchmarks predicting unemployment at baseline and employment worsening at 2 years were identified as the test scores with the minimum p-value in logistic regression models adjusting for age, sex and education. Odds ratios representing the risk of unemployment or employment worsening were calculated based on the identified benchmarks.

Results

4815 of 9585 participants (50%) were employed full-time at baseline. In the training set benchmarks for unemployment were: PST ≤44 correct, OR (95% CI) 5.3 (4.7, 6.0); MDT >28.7 seconds, OR 7.2 (6.3, 8.1); and WST >8 seconds, OR 6.7 (5.8, 7.7). For patients employed at baseline, benchmarks for worsening employment status were: PST ≤44 correct, OR 4.3 (3.1, 6.0); MDT >24 seconds, OR 3.3 (2.3, 4.6); and WST >7.6 seconds, OR 6.4 (4.7, 8.8). Benchmarks were confirmed in the validation set.

Conclusions

Clinically relevant neuroperformance test benchmarks for predicting unemployment and employment worsening were identified in a training set and confirmed in a validation set using a large real world MS population. Future research will determine early risk factors for these benchmarks in order to identify potential employment preservation strategies.

Disclosures: MS PATHS is sponsored 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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Clinical Trials Poster Presentation

P0184 - A novel approach to conducting Phase IV studies: The design of the global diroximel fumarate EXPERIENCE study initiative (ID 1313)

Speakers
Presentation Number
P0184
Presentation Topic
Clinical Trials

Abstract

Background

Diroximel fumarate (DRF) is an oral fumarate recently approved in the United States for relapsing forms of multiple sclerosis (MS). DRF demonstrated favorable gastrointestinal (GI) tolerability in clinical studies of MS patients (pts). Discontinuations due to GI adverse events (AEs) were low (0.7%) in an open-label 2-year study. In a randomized study versus dimethyl fumarate (DMF), fewer pts reported GI AEs (35%, 88/253 DRF vs 49%,123/251 DMF) and GI AEs leading to discontinuation (0.8% DRF vs. 4.8% DMF); GI AEs were less frequently reported as moderate/severe for DRF (23%, 20/88) vs DMF (40%, 49/123). It is important to characterize DRF persistence in a real-world setting and effectiveness across different patient types and geographies.

Objectives

To describe the novel design of the DRF EXPERIENCE (EXPloring diroximEl fumarate Real-world experIENCE) Study Initiative.

Methods

A Phase IV DRF study should collect data on meaningful real-world outcomes, including treatment persistence, real-world tolerability, and clinical effectiveness, including cognitive changes, to align with evolving treatment goals. As DRF was designed to reduce treatment burden, impact on quality of life should also be assessed. Country-specific nuances due to unique healthcare environments, ethnicity, and cultural considerations diminish the utility of a single-study design.

Results

The DRF EXPERIENCE Study Initiative uses a novel design comprising 4 individual studies, each conducted in different regions but anchored by a core protocol to characterize the early experience in pts initiating DRF per routine care. The core protocol defines a set of required assessments for each study, but also allows flexibility to include others that address country-specific research questions. The primary objective is to characterize persistence to DRF at 1 year. Core protocol assessments include relapse, disability, cognitive changes, and pt-reported Neuro-QoL. Each study will enroll ~200 pts; the pooled total sample size of ~800 will improve ability for subgroup analyses. Pts will be followed for 2 years and include those newly initiating a disease modifying therapy (DMT) or switching from previous DMTs (including prior DMF).

Conclusions

The DRF EXPERIENCE Study Initiative uses a novel design to characterize the improved GI tolerability profile and effectiveness of DRF in MS pts in the real-world and will be informative to providers and patients when considering MS treatment goals together with the burden of therapy.

Supported by: Biogen

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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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Presenter Of 2 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

P0120 - Neuroperformance test outcomes as predictors of employment in a large, heterogeneous real world MS populations: Results from MS PATHS (ID 1758)

Speakers
Presentation Number
P0120
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Neuro-performance testing has been used extensively in MS clinical trials, resulting in a large literature on processing speed (Symbol Digit Modalities Test [SDMT]), manual dexterity (9-Hole Peg Test [9HPT]), and walking speed (25-foot walk [25FW]). Computer adapted versions were developed and validated, to support widespread use in clinical practice. The Multiple Sclerosis Performance Test (MSPT) includes a self-administered Processing Speed Test (PST), simulating SDMT; Manual Dexterity Test (MDT), simulating 9HPT; and Walking Speed Test (WST), simulating 25FW. MSPT is deployed within the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network. Optimal test thresholds associated with employment status in a real-world population have not been reported.

Objectives

To determine thresholds for standardized test scores of processing speed, manual dexterity, and walking speed as predictors of employment status in a real world MS population.

Methods

Neuroperformance testing was done as part of clinical visits in MS PATHS. Employment status was collected via standardized questionnaire. Patients aged 18 to 60 in the US were divided into a training set (n=3210) and a test set (n=1605). PST, MDT and WST benchmarks predicting unemployment at baseline and employment worsening at 2 years were identified as the test scores with the minimum p-value in logistic regression models adjusting for age, sex and education. Odds ratios representing the risk of unemployment or employment worsening were calculated based on the identified benchmarks.

Results

4815 of 9585 participants (50%) were employed full-time at baseline. In the training set benchmarks for unemployment were: PST ≤44 correct, OR (95% CI) 5.3 (4.7, 6.0); MDT >28.7 seconds, OR 7.2 (6.3, 8.1); and WST >8 seconds, OR 6.7 (5.8, 7.7). For patients employed at baseline, benchmarks for worsening employment status were: PST ≤44 correct, OR 4.3 (3.1, 6.0); MDT >24 seconds, OR 3.3 (2.3, 4.6); and WST >7.6 seconds, OR 6.4 (4.7, 8.8). Benchmarks were confirmed in the validation set.

Conclusions

Clinically relevant neuroperformance test benchmarks for predicting unemployment and employment worsening were identified in a training set and confirmed in a validation set using a large real world MS population. Future research will determine early risk factors for these benchmarks in order to identify potential employment preservation strategies.

Disclosures: MS PATHS is sponsored by Biogen

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