Mount Sinai

Author Of 5 Presentations

Observational Studies Poster Presentation

LB1149 - Perceptions of risk and adherence to care in MS patients during the COVID-19 pandemic: a cross-sectional study (ID 825)

Speakers
Presentation Number
LB1149
Presentation Topic
Observational Studies

Abstract

Background

The COVID-19 pandemic has raised concerns for increased risk of infection in patients with multiple sclerosis (MS) and disrupted their routine MS care.

Objectives

The aim of this study is to characterize the extent of MS patients’ perceptions of risk and adherence to care during the pandemic.

Methods

A survey was emailed to patients from a large MS center in New York City during the local peak of the pandemic to assess perceptions of infection risk and adherence to MS care including appointments, laboratory studies, MRIs, and taking disease-modifying therapies (DMT).

Results

529 patients from the MS center responded to the survey during two-weeks in April 2020. Patients collectively showed concern about becoming infected with COVID-19 (88%) and perceived a higher infection risk because of having MS (70%) and taking DMTs (68%). Patients frequently postponed appointments (41%), laboratory studies (46%), and MRIs (41%). Noncompliance with DMTs was less common (13%). Decisions to alter usual recommendations for care were made by the patient more often than by the provider regarding adherence to appointments (68%), laboratory studies (70%), MRI (67%), and DMTs (65%). Degree of concern for infection was associated with adherence to appointments (p=0.020) and laboratory studies (p=0.016) but not with adherence to MRI and DMTs. Thirty-five patients reported being tested for COVID-19, of whom fourteen reported a positive test.

Conclusions

Patients with MS were highly concerned about becoming infected during the local peak of the COVID-19 pandemic. Behaviors that deviated from originally recommended MS care were common and often self-initiated, but patients were overall compliant with continuing DMTs.

Collapse
COVID-19 Late Breaking Abstracts

LB1205 - Covid-19 Infection in Patients with Multiple Sclerosis: an observational study by The New York COVID-19 Neuro-Immunology Consortium (NYCNIC) (ID 2054)

Abstract

Background

New York became one of the first epicenters of the COVID-19 pandemic in the United States and many neurologists were faced with the unprecedented challenge of providing medical advice to patients with multiple sclerosis (MS) without the support of evidence-based scientific data. Large collaborative studies are needed to determine whether MS itself, or associated disease-modifying therapies (DMT), increase the risk of acquiring COVID-19 or worsen its course.

Objectives

We aim to characterize the patterns of COVID-19 infection in patients with MS and to identify risk factors for severe infection.

Methods

Demographics, MS and COVID-19 clinical features were collected on patients currently followed at 5 large MS Centers in New York City and the tri state area (MSSM, Columbia, Northwell, NYU, and Neurological Associates Of Long Island). Patients with MS or related disorders, who self-identified as diagnosed with COVID-19 by a healthcare provider (based on characteristic symptoms, radiographic findings and/or positive COVID-19 PCR/serology when available) were included. The severity of COVID-19 infection was measured by a 4-point ordinal scale (home care, hospitalization, ICU, death). Univariate and multivariate logistic regression models were used to assess associations of demographic variables with hospitalization.

Results

Our cohort included 349 patients with median age of 45 (range 13-76), 70.8% female, 25.3% African-American, 23.7% Hispanic. Mean disease duration was 11.5y [SD 9.1]. The prevalence of DMT use was 87.2%, and 80.2% were ambulatory without assistance. Forty-eight (14.2%) patients were hospitalized, and 13 (3.9%) patients died. Multivariate logistic regression models showed associations between EDSS ≥6 (OR 3.9 [95% CI, 1.7-8.8]), obesity (OR 2.4 [95% CI, 1.1-4.9]) and age (OR per 10 year increase: 1.5 [95% CI, 1.1-2.2]) with hospitalization for COVID-19. There were no significant associations between race, ethnicity, comorbidities (cardiac, pulmonary or diabetes), smoking status, or specific DMT and severe COVID-19 infection requiring hospitalization.

Conclusions

Age, obesity, and higher EDSS independently predicted severe COVID -19 infection necessitating hospitalization. This is in agreement with COVID -19 outcome predictors in the general population and other MS cohorts. Older patients with limited mobility should be counseled to maintain increased vigilance during the ongoing pandemic.

Collapse
Clinical Outcome Measures Poster Presentation

P0059 - Defining predictors of disease activity and worsening in multiple sclerosis: an analysis of the CombiRx trial (ID 828)

Speakers
Presentation Number
P0059
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes.

Objectives

The aim of the study is to identify and assess clinical characteristics in MS that predict disease activity and progression.

Methods

The study population consisted of a prospective cohort of 1,008 patients with relapsing-remitting (RR) onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics (age <38 vs. ≥38, sex, race), clinical history (number of relapses in prior year <3 vs. ≥3, disease duration, Expanded Disability Status Scale (EDSS)), and MRI metrics (presence or absence of gadolinium (Gd) and number of T2 lesions), and treatment (glatiramer acetate (GA), interferon-beta 1a (IFN), or combination therapy); with outcomes of time to first new disease activity over 7-years of follow-up including relapse, MRI activity defined by new combined unique active lesion, and disease worsening as defined by confirmed 6-month increase in EDSS.

Results

1,008 participants were randomized, with 959 eligible for assessment of disease worsening and activity on follow-up MRI. Participants were median 38 (range 18, 61) years of age at baseline, 72.7% female, 88.3% Caucasian, 7.1% black/African American, mean 1.2 years since diagnosis, with median 2 relapses in the prior 12 months and median EDSS 2 (IQR 1, 2.5). Risk of relapse was higher in patients younger than 38 at BL vs. older (HR 1.36, 95% CI: 1.12,1.65) and with BL EDSS ≥3.5 vs. <3.5 (HR 1.66, 95% CI: 1.27, 2.14). Presence of Gd+ lesions at baseline was also associated with increased risk of relapse (HR 1.37, 95%CI: 1.14, 1.66). Risk of new MRI activity was higher in younger participants (HR 1.56, 95%CI: 1.34, 1.86) and those taking either single agent arms compared to the combination (GA: HR 1.48, 95%CI 1.22, 1.80; IFN: HR 1.43, 95%CI 1.18, 1.74). Similarly, higher preexisting lesion burden greater than the median lesion count with ≥71 T2 hyperintense lesions vs. <71 (HR 1.50, 95%CI 1.27, 1.78) and presence of BL Gd+ lesions (HR 1.75, 95%CI: 1.49, 2.06) were also associated with a higher risk of developing new MRI activity. Risk of disease worsening was higher for those with BL EDSS < 2 (HR 2.79, 95%CI 2.14, 3.67). There were no associations between sex and disease duration on clinical or radiological disease activity or worsening.

Conclusions

Both clinical and radiological disease activity are predicted by younger age and presence of Gd+ lesions. Additionally, relapses are also predicted by higher EDSS, and there is some protective evidence of the combination therapy in lowering risk of new MRI activity. Only baseline EDSS level was associated with disease worsening.

Collapse
Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0340 - High-dimensional immune profiling of dimethyl fumarate and ocrelizumab in multiple sclerosis (ID 1007)

Speakers
Presentation Number
P0340
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Dimethyl fumarate (DMF) and ocrelizumab are two effective immunomodulators for multiple sclerosis (MS). Identifying overlapping mechanisms of action between the drugs may elucidate common pathways in preventing disease activity.

Objectives

In this study we analyzed cytokine and immune-profiling data to evaluate the similarities and differences between these two disease-modifying therapies in MS.

Methods

Plasma and PBMCs from MS patients were collected at baseline, 3 months and 6 months after treatment with DMF (n=16) and ocrelizumab (n=13). Immunophenotyping was performed with mass cytometry (CyTOF) and analyzed with gating based on cell surface markers. Cytokine analysis from plasma was performed with Olink assays and analyzed with linear mixed effects models.

Results

DMF reduced both effector T and memory B cell populations while increasing CD56bright natural killer (NK) cells. Ocrelizumab exerted its main immunomodulatory effect by reducing the frequency of all B cells and increasing frequency of NK cells. At 6 months, naïve B-cells began to reconstitute; however, memory B cells remain depleted. DMF treatment was associated with a significant reduction of plasma cytokines involved in inflammatory pathways, such as IL-6 and IL-12 signaling in MS and Dectin-1 signaling. In addition, DMF lowered plasma cytokines that are dysregulated in psoriasis and involved in allograft rejection pathways. Ocrelizumab treatment led to the upregulation of neurotropic proteins in the plasma of MS patients, including proteins involved in NAD biosynthesis and tryptophan metabolism.

Conclusions

Our high-dimensional immunophenotyping results suggest that DMF and ocrelizumab both increase NK cells in addition to affecting different immune cell populations and cytokine pathways to exert their effects in MS patients. Detecting similarities between the mechanisms of the two drugs may contribute to identifying more specific therapeutic targets.

Collapse
Comorbidities Poster Presentation

P0434 - Associations of depression and anxiety with disease-activity and disability in multiple sclerosis: an analysis of baseline participant characteristics from the CombiRx trial (ID 1176)

Speakers
Presentation Number
P0434
Presentation Topic
Comorbidities

Abstract

Background

Depression and anxiety have increased prevalence in multiple sclerosis (MS). There are limited studies on associations of depression and anxiety with MS disease characteristics.

Objectives

The aim of the study is to identify and quantify associations of depression and anxiety with MS disease activity and disability.

Methods

The study population included a prospective cohort of 1008 treatment-naïve participants with relapsing-remitting (RR) MS enrolled in the CombiRx trial. Entrance criteria included at least 2 relapses in the prior 2 years. Covariate adjusted linear regression analyses were conducted to determine associations and adjusted R-squared (R2) between baseline scores on three components of the Multiple Sclerosis Quality of Life Index (MSQLI): the Mental Health Inventory (MHI), Depression Subscale (MHD), and Anxiety Subscale (MHA), where lower scores indicated more severe symptoms on each component of the MSQLI subscale; with outcomes of baseline MS disease characteristics including Expanded Disability Status Scale (EDSS) and total MRI lesion volume (T1+T2). Kruskal-Wallace comparison was used to assess prior relapse frequency (0, 1-2, and 3 or more in prior 12 months) and median MSQLI measures.

Results

Lower EDSS scores were associated with higher MHI scores (β = -0.31, R² = 0.1274, p <0.0001), higher MHA scores (β = -0.21, R² = 0.1060, p <0.0001), and higher MHD (β = -0.22, R² = 0.1096, p <0.0001), when adjusted for age and sex at baseline. Baseline MHA score was modestly associated with relapse frequency (p =0.043), with a median rank MHA score of 5 for 0 relapses, 4.6 for 1-2 relapses, and 4.6 for ≥3 relapses. Components of the MSQLI were not associated with MRI lesion volume.

Conclusions

Depression and anxiety in MS are associated with increased baseline EDSS disability. Of the three measures, only anxiety was associated with higher baseline relapse frequency. A follow-up analysis is planned to examine associations of depression and anxiety on longitudinal MS disease outcomes in the trial cohort.

Collapse

Presenter Of 4 Presentations

Observational Studies Poster Presentation

LB1149 - Perceptions of risk and adherence to care in MS patients during the COVID-19 pandemic: a cross-sectional study (ID 825)

Speakers
Presentation Number
LB1149
Presentation Topic
Observational Studies

Abstract

Background

The COVID-19 pandemic has raised concerns for increased risk of infection in patients with multiple sclerosis (MS) and disrupted their routine MS care.

Objectives

The aim of this study is to characterize the extent of MS patients’ perceptions of risk and adherence to care during the pandemic.

Methods

A survey was emailed to patients from a large MS center in New York City during the local peak of the pandemic to assess perceptions of infection risk and adherence to MS care including appointments, laboratory studies, MRIs, and taking disease-modifying therapies (DMT).

Results

529 patients from the MS center responded to the survey during two-weeks in April 2020. Patients collectively showed concern about becoming infected with COVID-19 (88%) and perceived a higher infection risk because of having MS (70%) and taking DMTs (68%). Patients frequently postponed appointments (41%), laboratory studies (46%), and MRIs (41%). Noncompliance with DMTs was less common (13%). Decisions to alter usual recommendations for care were made by the patient more often than by the provider regarding adherence to appointments (68%), laboratory studies (70%), MRI (67%), and DMTs (65%). Degree of concern for infection was associated with adherence to appointments (p=0.020) and laboratory studies (p=0.016) but not with adherence to MRI and DMTs. Thirty-five patients reported being tested for COVID-19, of whom fourteen reported a positive test.

Conclusions

Patients with MS were highly concerned about becoming infected during the local peak of the COVID-19 pandemic. Behaviors that deviated from originally recommended MS care were common and often self-initiated, but patients were overall compliant with continuing DMTs.

Collapse
Clinical Outcome Measures Poster Presentation

P0059 - Defining predictors of disease activity and worsening in multiple sclerosis: an analysis of the CombiRx trial (ID 828)

Speakers
Presentation Number
P0059
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes.

Objectives

The aim of the study is to identify and assess clinical characteristics in MS that predict disease activity and progression.

Methods

The study population consisted of a prospective cohort of 1,008 patients with relapsing-remitting (RR) onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics (age <38 vs. ≥38, sex, race), clinical history (number of relapses in prior year <3 vs. ≥3, disease duration, Expanded Disability Status Scale (EDSS)), and MRI metrics (presence or absence of gadolinium (Gd) and number of T2 lesions), and treatment (glatiramer acetate (GA), interferon-beta 1a (IFN), or combination therapy); with outcomes of time to first new disease activity over 7-years of follow-up including relapse, MRI activity defined by new combined unique active lesion, and disease worsening as defined by confirmed 6-month increase in EDSS.

Results

1,008 participants were randomized, with 959 eligible for assessment of disease worsening and activity on follow-up MRI. Participants were median 38 (range 18, 61) years of age at baseline, 72.7% female, 88.3% Caucasian, 7.1% black/African American, mean 1.2 years since diagnosis, with median 2 relapses in the prior 12 months and median EDSS 2 (IQR 1, 2.5). Risk of relapse was higher in patients younger than 38 at BL vs. older (HR 1.36, 95% CI: 1.12,1.65) and with BL EDSS ≥3.5 vs. <3.5 (HR 1.66, 95% CI: 1.27, 2.14). Presence of Gd+ lesions at baseline was also associated with increased risk of relapse (HR 1.37, 95%CI: 1.14, 1.66). Risk of new MRI activity was higher in younger participants (HR 1.56, 95%CI: 1.34, 1.86) and those taking either single agent arms compared to the combination (GA: HR 1.48, 95%CI 1.22, 1.80; IFN: HR 1.43, 95%CI 1.18, 1.74). Similarly, higher preexisting lesion burden greater than the median lesion count with ≥71 T2 hyperintense lesions vs. <71 (HR 1.50, 95%CI 1.27, 1.78) and presence of BL Gd+ lesions (HR 1.75, 95%CI: 1.49, 2.06) were also associated with a higher risk of developing new MRI activity. Risk of disease worsening was higher for those with BL EDSS < 2 (HR 2.79, 95%CI 2.14, 3.67). There were no associations between sex and disease duration on clinical or radiological disease activity or worsening.

Conclusions

Both clinical and radiological disease activity are predicted by younger age and presence of Gd+ lesions. Additionally, relapses are also predicted by higher EDSS, and there is some protective evidence of the combination therapy in lowering risk of new MRI activity. Only baseline EDSS level was associated with disease worsening.

Collapse
Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0340 - High-dimensional immune profiling of dimethyl fumarate and ocrelizumab in multiple sclerosis (ID 1007)

Speakers
Presentation Number
P0340
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Dimethyl fumarate (DMF) and ocrelizumab are two effective immunomodulators for multiple sclerosis (MS). Identifying overlapping mechanisms of action between the drugs may elucidate common pathways in preventing disease activity.

Objectives

In this study we analyzed cytokine and immune-profiling data to evaluate the similarities and differences between these two disease-modifying therapies in MS.

Methods

Plasma and PBMCs from MS patients were collected at baseline, 3 months and 6 months after treatment with DMF (n=16) and ocrelizumab (n=13). Immunophenotyping was performed with mass cytometry (CyTOF) and analyzed with gating based on cell surface markers. Cytokine analysis from plasma was performed with Olink assays and analyzed with linear mixed effects models.

Results

DMF reduced both effector T and memory B cell populations while increasing CD56bright natural killer (NK) cells. Ocrelizumab exerted its main immunomodulatory effect by reducing the frequency of all B cells and increasing frequency of NK cells. At 6 months, naïve B-cells began to reconstitute; however, memory B cells remain depleted. DMF treatment was associated with a significant reduction of plasma cytokines involved in inflammatory pathways, such as IL-6 and IL-12 signaling in MS and Dectin-1 signaling. In addition, DMF lowered plasma cytokines that are dysregulated in psoriasis and involved in allograft rejection pathways. Ocrelizumab treatment led to the upregulation of neurotropic proteins in the plasma of MS patients, including proteins involved in NAD biosynthesis and tryptophan metabolism.

Conclusions

Our high-dimensional immunophenotyping results suggest that DMF and ocrelizumab both increase NK cells in addition to affecting different immune cell populations and cytokine pathways to exert their effects in MS patients. Detecting similarities between the mechanisms of the two drugs may contribute to identifying more specific therapeutic targets.

Collapse
Comorbidities Poster Presentation

P0434 - Associations of depression and anxiety with disease-activity and disability in multiple sclerosis: an analysis of baseline participant characteristics from the CombiRx trial (ID 1176)

Speakers
Presentation Number
P0434
Presentation Topic
Comorbidities

Abstract

Background

Depression and anxiety have increased prevalence in multiple sclerosis (MS). There are limited studies on associations of depression and anxiety with MS disease characteristics.

Objectives

The aim of the study is to identify and quantify associations of depression and anxiety with MS disease activity and disability.

Methods

The study population included a prospective cohort of 1008 treatment-naïve participants with relapsing-remitting (RR) MS enrolled in the CombiRx trial. Entrance criteria included at least 2 relapses in the prior 2 years. Covariate adjusted linear regression analyses were conducted to determine associations and adjusted R-squared (R2) between baseline scores on three components of the Multiple Sclerosis Quality of Life Index (MSQLI): the Mental Health Inventory (MHI), Depression Subscale (MHD), and Anxiety Subscale (MHA), where lower scores indicated more severe symptoms on each component of the MSQLI subscale; with outcomes of baseline MS disease characteristics including Expanded Disability Status Scale (EDSS) and total MRI lesion volume (T1+T2). Kruskal-Wallace comparison was used to assess prior relapse frequency (0, 1-2, and 3 or more in prior 12 months) and median MSQLI measures.

Results

Lower EDSS scores were associated with higher MHI scores (β = -0.31, R² = 0.1274, p <0.0001), higher MHA scores (β = -0.21, R² = 0.1060, p <0.0001), and higher MHD (β = -0.22, R² = 0.1096, p <0.0001), when adjusted for age and sex at baseline. Baseline MHA score was modestly associated with relapse frequency (p =0.043), with a median rank MHA score of 5 for 0 relapses, 4.6 for 1-2 relapses, and 4.6 for ≥3 relapses. Components of the MSQLI were not associated with MRI lesion volume.

Conclusions

Depression and anxiety in MS are associated with increased baseline EDSS disability. Of the three measures, only anxiety was associated with higher baseline relapse frequency. A follow-up analysis is planned to examine associations of depression and anxiety on longitudinal MS disease outcomes in the trial cohort.

Collapse