Background

Risk factors previously identified for worse outcomes with SARS-CoV-2 infections include older age, male sex and specific comorbid conditions. An increased risk for poorer COVID-19 outcomes in people with multiple sclerosis (MS) are similar to the general population, but less is known about outcomes in minority groups with MS.

Objectives

To evaluate differences in outcomes of SARS-CoV-2 infection in non-Hispanic White and Black persons with multiple sclerosis.

Methods

COViMS is a North American registry for health care providers to report persons with MS who are infected with SARS-CoV-2, the virus that causes COVID-19 (cases). Cases are reported after 7 days and when the outcome of infection is reasonably certain. MS and clinically isolated syndrome cases were categorized using the Center for Disease Control and Prevention races (non-Hispanic Whites, and Black). Comorbidities related to COVID-19 outcomes were collected. Clinical outcomes examined were mortality alone, mortality and/or admissions to the intensive care unit (ICU) and mortality, ICU admissions and/or hospitalization. Age-adjusted mortality rates as of August 3, 2020 and 95% confidence intervals (CI) were calculated. Multivariable logistic regression was used to assess adjusted differences between races using odds ratios (OR) and 95% CIs. Covariates included sex, age, smoking (current, past, never), MS clinical course (relapsing, progressive), disease duration, ambulation (fully ambulatory, walks with assistance, non-ambulatory), individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease modifying therapy use (yes vs no).

Results

Of 734 patients reported, 421 (57.4%) Whites, and 194 (26.5%) Black patients were reported. Black cases were more likely to be younger (p=0.002), never smokers (p=0.002), have shorter MS duration (p<0.001), a relapsing MS course (p=0.03) and have comorbidities (p<0.001) compared to Whites. A higher proportion of Black patients had hypertension (40.2% vs 19.5%, p<0.001), and morbid obesity (17.0% vs 9.5%, p=0.007). Mortality rates increased with age and were not statistically different between Whites and Blacks (p=0.156). Black race was associated with increased odds of mortality and/or ICU admission (OR 3.8 [95%CI: 1.60, 8.96], p=0.002) and mortality, ICU admission and/or hospitalization (OR 2.0 [95%CI: 1.14, 3.54], p=0.016) after adjustment for covariates.

Conclusions

Within the COViMS registry, Black MS patients were younger and more likely to have comorbidities than White MS patients. Black MS patients had an increased risk for poorer outcomes compared to Whites even after adjusting for comorbidities at the time of COVID-19.

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.

Background

Pre-existing chronic illness is associated with increased psychiatric distress due to the spread of COVID-19, specifically increased stress, anxiety and depression. This potentially placed individuals with MS in a uniquely vulnerable position to experience greater psychiatric symptomatology.

Objectives

To examine the impact of the COVID-19 pandemic on emotional symptomatology and quality of life in individuals with Progressive Multiple Sclerosis (PMS).

Methods

Data were obtained during a randomized clinical trial on rehabilitation taking place at 11 centers in North America and Europe (The CogEx Trial, ClinicalTrials.gov Identifier: NCT03679468). Participants included 131 individuals with PMS. Study procedures were interrupted in accordance with governmental restrictions as COVID-19 spread. During study closure, a COVID Impact Survey was administered via telephone or email to all participants, along with patient report outcome (PRO) measures of depressive and anxiety symptoms, quality of life and MS symptomatology that were previously administered pre-pandemic.

Results

The time between baseline PRO completion and lockdown survey completion varied (M=9.5 months, SD=4.1 months). 4% of respondents reported COVID-19 infection. No significant changes were noted in anxiety, quality of life, or the impact of MS symptomatology on daily life from baseline to lockdown. While total HADS depression scores increased significantly at follow up, this did not translate into more participants scoring above the HADS threshold for clinically significant depression. No significant relationships were noted between disease duration, processing speed ability or EDSS and changes in symptoms of depression or anxiety.

Most participants reported impact of the virus on their psychological well-being, with little impact on financial well-being. Perceived impact of the pandemic on physical and psychological well-being correlated significantly with the impact of MS symptomatology on daily life, as well as changes in depression.

Conclusions

Overall, in a sample confined exclusively to people with chronic progressive MS, little clinically significant change was noted in symptoms of depression or anxiety or quality of life during the pandemic lockdown.

Background

Emergence of SARS CoV-2 causing COVID-19 provoked the need to gather information on the overall outcomes and potential risks associated with morbidity and mortality in multiple sclerosis (MS) patients with COVID-19 infections. The COViMS registry was initiated as a rapid and efficient means to collect this data from North American health care providers.

Objectives

To describe the spectrum of outcomes in SARS CoV-2 infected North American MS patients and to ascertain characteristics associated with severe COVID-19 outcomes.

Methods

The COViMS registry requested that MS, neuromyelitis optica (NMO), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), and radiographically isolated syndrome (RIS) patients with SARS-CoV-2 infection be reported after the outcome was reasonably certain. Data were de-identified and cross-sectional. Effort was made to harmonize with other international registries for COVID-19. Poor clinical outcomes assessed were: mortality, mortality and/or admission to the intensive care unit (ICU), and mortality, ICU admission and/or hospitalization. Associations between patient characteristics and these outcomes were evaluated using multivariable logistic regression. Covariates included sex, age, race, smoking, MS clinical course (relapsing, progressive), MS disease duration, ambulation (fully ambulatory, walks with assistance, non-ambulatory), individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease modifying therapy (DMT) use.

Results

As of Aug 3, 2020, 764 patients from over 140 different practices were reported; 734 MS, 21 NMO, 4 MOGAD, and 5 RIS. MS patients were 73.4% female (73.4%), 65.2% Caucasian, with mean (SD) age of 48.2 (±13.5) years. Mean disease duration was 13.8 (±9.9) years. 70.9% were fully ambulatory. Ocrelizumab and dimethyl fumarate (DMF) were the top two DMTs used. Most (77.1%) were laboratory confirmed for SARS-CoV-2. Of MS cases, 6.1% died, 13.8% were admitted to the ICU and/or died, and 31.2% were either hospitalized, admitted to the ICU or died. Older age, non-ambulatory status and cardiovascular disease were associated with increased risk of poor outcomes. No specific DMT was associated with increased odds of mortality and mortality and/or ICU admission. Anti-CD20 DMT use showed an increased odds of mortality, ICU admission and/or hospitalization compared to DMF (OR: 2.53 95%CI [1.17, 5.50]).

Conclusions

The data provide reassurance that the MS registry population aligns with reported COVID-19 outcomes in the general North American population. While reported deaths are few, no clear association between a specific therapy and mortality has been seen after adjustment for age, sex, ambulatory status and comorbidities. Data collection continues.

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.

Background

In clinical trials, the probability of confirmed disability worsening (CDW) is significantly lower with intramuscular (IM) interferon beta-1a (IFNβ1a) and peginterferon beta-1a (PEG) treatment than with placebo in patients with relapsing forms of multiple sclerosis (RMS). Registry data provides information on disability outcomes with long-term treatment.

Objectives

To examine the long-term effects of IM IFNβ1a and PEG on real-world effectiveness in participants with RMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry.

Methods

This analysis included NARCOMS participants diagnosed with RMS who initiated IM IFNβ1a treatment between April 2004 and October 2019 (N=760) or PEG between October 2014 and October 2019 (N=116). Patient-reported outcomes were collected every 6 months. The primary endpoint was 6-month CDW, defined as a ≥1-point increase in Patient Determined Disease Steps (PDDS) score sustained for ≥6 months. Separate analyses were conducted in the IM IFNβ1a and PEG cohorts. A Kaplan-Meier analysis assessed the cumulative probability of CDW; participants were censored if they discontinued treatment or had no additional follow-up. Only participants who completed ≥2 surveys with treatment history and ≥3 surveys with PDDS history were included in the CDW analysis (IM IFNβ1a: N=760; PEG: n=81). Progression to secondary progressive multiple sclerosis (SPMS) was analysed in IM IFNβ1a participants who completed ≥50% of their surveys (n=630) and in PEG participants (n=102).

Results

At the first survey on treatment in IM IFNβ1a and PEG participants, the mean age was 49.7 and 53.0 years, respectively, the mean (standard deviation [SD]) disease duration was 11.1 (8.6) and 15.8 (7.9) years, respectively, and 8.4% and 91.2% had prior disease modifying therapy (DMT) use, respectively. The median PDDS score at the first survey was 2.0 for both populations, indicating moderate disability. The cumulative probability of remaining free of CDW was 77.6% and 43.6% at 2 and 11 years of IM IFNβ1a treatment, respectively, and 84.4% at 2 years of PEG treatment. The cumulative probability of participant-reported progression to SPMS was 1.2% and 12.0% at 2.5 and 11 years in IM IFNβ1a participants, respectively, and 3.3% at 2.5 years in PEG participants.

Conclusions

These results support clinical trial data showing the effectiveness of IM IFNβ1a and PEG in preventing CDW and demonstrate their long-term effectiveness in RMS patients.

This study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).

Background

In the pivotal trials of ocrelizumab (OCR) in patients with relapsing-remitting multiple sclerosis (RRMS; OPERA I, OPERA II), ≈75% of participants had no previous disease-modifying therapy (DMT).

Objectives

To report 2-year findings from the Phase IIIb CHORDS study (NCT02637856) investigating OCR in patients with RRMS who had a suboptimal response with previous DMT.

Methods

CHORDS enrolled patients who had a suboptimal response (≥1 relapse, ≥1 T1 gadolinium [Gd]-enhancing lesion or ≥2 new/enlarging T2 lesions) after ≥6 months of treatment with 1 to 3 previous DMTs. All participants received OCR 600 mg every 24 weeks for 96 weeks and were included in the intention-to-treat (ITT) population. Annualized relapse rate (ARR), changes in Expanded Disability Status Scale (EDSS) and safety were assessed in the ITT population. The primary endpoint was the proportion of patients free of any protocol-defined event (i.e. relapse, T1 Gd-enhancing lesion, new/enlarging T2 lesion, 24-week confirmed disability progression [CDP] on the EDSS) and was evaluated using a modified ITT (mITT) population, which imputed as having an event those patients who terminated early for lack of efficacy or death and excluded patients who discontinued for reasons other than an event.

Results

The ITT population included 608 patients with a mean (SD) time since diagnosis of 4.2 (3.03) years. The most frequently used DMTs prior to enrollment included glatiramer acetate (49.3%), dimethyl fumarate (35.4%) and fingolimod (20.1%). In the mITT population (576 [94.7%]), 48.1% of patients were free of all protocol-defined events, and most experienced freedom from individual events (relapse, 89.6%; T1 Gd-enhancing lesions, 95.5%; new/enlarging T2 lesions, 59.5%; 24-week CDP, 89.6%) over 96 weeks. Similar results were observed for the primary endpoint in those who received 1 vs >1 prior DMT (50.9% vs 44.5%) as well as for individual events (relapse, 90.0% vs 89.2%; T1 Gd-enhancing lesion, 95.8% vs 95.1%; new/enlarging T2 lesion, 61.4% vs 57.1%; 24-week CDP, 90.9% vs 87.9%). The adjusted ARR over 96 weeks was 0.046. Most patients had stable (<1-point change; 61.5%) or improved (≥1-point decrease; 22.7%) EDSS scores. There were no deaths or new safety signals.

Conclusions

This analysis demonstrates the potential benefits of ocrelizumab treatment over 2 years in patients with RRMS who are relatively early in the disease course and have experienced suboptimal response on prior DMTs.

Background

The North American Research Committee on Multiple Sclerosis (NARCOMS) registry is a voluntary self-report registry for persons with MS. Interest has been growing over time regarding the benefits of cannabis for management of various symptoms in MS, particularly as cannabis becomes more accessible.

Objectives

To evaluate the contemporary prevalence of cannabis use among persons with MS, and demographic factors associated with cannabis use for MS symptom management.

Methods

Active US NARCOMS participants were invited to complete an online, supplemental survey regarding cannabis use (excluding hemp CBD and products labeled as CBD only) for their MS symptoms. Demographic and clinical characteristics captured included age, sex, race, state of residence, age at MS symptom onset, and disability level measured using the Patient Determined Disease Steps (PDDS). Participant-reported symptoms of spasticity, pain, and sleep problems were captured using a numeric rating scale (NRS) with scores ranging from 0 (no problems) to 10 (worst possible problems). For the analysis we categorized NRS scores as 0 (normal), 1-3 (mild), 4–6 (moderate), and 7–10 (severe). We summarized the findings using descriptive statistics.

Results

Of the 6934 participants invited, 3249 (46.9%) responded. Most respondents were female (78.5%), Caucasian (88.5%), and had a mean (SD) age of 61.2 (10.2) years. The respondents had a mean age at symptom onset of 31.2 (10.3) years, and a median (25^th, 75^th) PDDS level of 3 [Gait Disability] (1 [Mild Disability], 6 [Bilateral Support]). Over 60% of respondents reported moderate to severe spasticity, pain, or sleep problems. Thirty-one percent of respondents (n=1012) indicated they had used cannabis for their MS symptoms at least once; of these respondents, 50.5% had used cannabis to treat spasticity, 43.6% had used cannabis for pain, and 38.4% had used cannabis for sleep. There were 636 (19.6%) respondents who reported current use of cannabis for their MS, while 376 (11.6%) reported past use but not current use. Current users were comparable to past users except current users were more likely to be male (p=0.001) and on average slightly younger (p=0.009).

Conclusions

In this US registry-based sample, 31% of participants reported ever using cannabis for MS symptoms, and 20% reported current use within the prior 30 days.