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

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

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

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

Background

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) registry is a physician-based registry/longitudinal database for patients with multiple sclerosis (MS). NARCRMS may elucidate the patient characteristics of underserved populations such as Blacks/African Americans (AA) and Hispanics/Latinos.

Objectives

To describe the socio-demographic and clinical characteristics of patients presenting with relapsing-remitting MS (RRMS) within the NARCRMS registry by race and ethnicity.

Methods

The NARCRMS registry contains data of MS patients aged 18-50 years across 24 sites from the US and Canada. This exploratory analysis describes characteristics of patients who enrolled between December 2016 and May 2020 (N=722), including age, gender, education, income level and occupation, Expanded Disability Status Scale (EDSS) categories, and disease-modifying therapy (DMT) categories/DMT use. Patient characteristics were summarized by frequencies and proportions for categorical variables and by means, standard deviations (SDs) and medians for continuous variables.

Results

The mean age (SD) of patients in this study was 40.1 (10.4) years; 71% were female. Majority (85%, n=587/695) were White; Black/AA patients comprised 11% (n=74/695). Educational attainment was comparable between races ― 22-24% with a high school degree, and 47-49% with an undergraduate degree. However, more Black/AA than White patients were unemployed (8%, n=6/72 vs 3%, n=15/565) or had an annual income <$15K (16%, n=12/73 vs 6%, n=35/573). Overall, 72% of patients had mild MS (EDSS scores 0‒2.5). However, twice as many Blacks/AAs had substantial disability (EDSS score ≥4.0) vs Whites (20%, n=15/74 vs 9.7%, n=57/587, respectively). Over half of all patients (57%, n=370/646) were treated with DMTs, with 50% (n=198) using injectables and 37% (n=147) using oral DMTs. Hispanics comprised 24% (n=152/646) of the patients, including Black/AA-Hispanic (3%, n=19/646) and White-Hispanic (21%, n=133/646). Hispanic patients were less likely than non-Hispanics to use DMTs, 43% (n=65/152) vs 62% (n=305/494). Of the subgroups, Black/AA-Hispanics were least likely to use DMTs (26%, n=5/19).

Conclusions

Blacks/AAs present with more severe disability than White patients. More Hispanics than non-Hispanics are not treated with DMTs. Real-world data show disparities in socio-demographic and clinical characteristics of patients with MS.

Supported by: Biogen

Background

Magnetic resonance imaging (MRI) can supplement clinical diagnostic criteria for multiple sclerosis (MS) by increasing diagnostic sensitivity and predicting the onset of clinically definite MS (CDMS).

Objectives

To determine whether the number of gadolinium-enhanced (Gd⁺) lesions and T2 volume at baseline (BL) may be predictors of CDMS.

Methods

RENEW (NCT01721161) was a randomised, double-blind, placebo-controlled study of participants with a first episode of acute optic neuritis who were treated with opicinumab 100 mg/kg once every 4 weeks (6 doses) and followed-up to week 32. Eligible participants were enrolled in RENEWED (NCT02657915), a 1-day follow-up (Day 1) at 2 years, to study the long-term electrophysiologic and clinical outcomes of treatment with opicinumab vs. placebo. Severity of disease using brain MRI was a secondary efficacy endpoint. In a post hoc analysis of brain MRI lesions, the number of Gd⁺ lesions and volume of T2 lesions at BL in RENEW were assessed for predicting CDMS at Day 1 of RENEWED for the intention-to-treat (ITT) and per protocol (PP) populations. Primary analyses were performed in the PP population.

Results

The numbers of RENEW participants who completed RENEWED were 52/82 in the ITT population (opicinumab, n=28; placebo, n=24) and 47/69 in the PP population (opicinumab, n=24; placebo, n=23). In the PP population, 40/47 (85%) did not have CDMS prior to enrollment in RENEW; 24/40 at-risk participants (opicinumab n=12; placebo n=12) developed CDMS from enrollment in RENEW up to Day 1 in RENEWED. Median time to CDMS diagnosis after enrollment in RENEW was 909.5 days in the opicinumab group and 386.0 days in the placebo group. CDMS developed in participants with Gd⁺ lesions and enlarged T2 volumes at RENEW baseline. The hazard ratios (95% CI; p-value) of MRI measures at BL were: presence of Gd⁺ lesions, 11.52 (2.20, 60.25; p<0.001); number of Gd⁺ lesions, 6.78 (1.97, 23.35; p=0.0024); and T2 volume, 1.80 (1.34, 2.43; p=0.0001). Participants who did not develop CDMS had no Gd⁺ lesions at BL and had lower T2 volumes compared with participants who developed CDMS. Results were comparable in the ITT population. No differences were found in the risk of converting to CDMS in participants treated with opicinumab vs. placebo in either the ITT or PP populations.

Conclusions

The number of Gd⁺ lesions and T2 volume at BL may predict the onset of CDMS. A limitation of this study is its small sample size.

Supported 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

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