University of California San Francisco
Neurology

Author Of 1 Presentation

Invited Presentations Invited Abstracts

PS12.01 - Gender Based Approach to MS Therapeutics

Speakers
Authors
Presentation Number
PS12.01
Presentation Topic
Invited Presentations
Lecture Time
09:15 - 09:30

Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

PS12.01 - Gender Based Approach to MS Therapeutics

Speakers
Authors
Presentation Number
PS12.01
Presentation Topic
Invited Presentations
Lecture Time
09:15 - 09:30

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

PS12.01 - Gender Based Approach to MS Therapeutics

Speakers
Authors
Presentation Number
PS12.01
Presentation Topic
Invited Presentations
Lecture Time
09:15 - 09:30

Author Of 12 Presentations

Biosensors Poster Presentation

LB1144 - How does Coronavirus Disease 2019 (COVID-19) “Sheltering in Place” Affect Ambulatory Activity in People with Multiple Sclerosis? (ID 327)

Speakers
Presentation Number
LB1144
Presentation Topic
Biosensors

Abstract

Background

People with neurological conditions that impair mobility such as multiple sclerosis (MS) have low levels of physical activity, with walking their primary form of exercise. When the San Francisco Bay Area shelter-in-place order was announced in mid-March 2020 to flatten the curve of SARS-CoV-2 infections, the abrupt closure of gyms, fitness studios, and malls greatly limited options for safe exercise. We leveraged an ongoing study utilizing wearable technology, to understand the impact of the pandemic and the shelter-in-place policy on physical activity in people with MS (PwMS) at-risk for neurological worsening.

Objectives

To test the hypothesis that the average daily step count (STEPS) in people with MS would decrease due to the COVID-19 shelter-in-place order.

Methods

Average daily step count (STEPS) was measured from a large UCSF MS Center cohort of PwMS using a wrist-worn accelerometer (Fitbit Flex2) as previously detailed. STEPS before and after the shelter-in-place were available for 42 participants. Amount, type and frequency of exercise, as well as fatigue (Modified Fatigue Index; MFIS-5) and mental health (Mental Health Inventory; MHI-5) were assessed via questionnaire. The UCSF Institutional Review Board approved the study protocol. Descriptive statistics and pre-post comparisons using Wilcoxon Signed-rank were performed, and figures generated, using R studio.

Results

A decrease in STEPS was observed during the week (p =0.024), and month (p=0.048) after versus before the shelter-in-place order in 42 participants with valid STEPS data during this time period. Individual data showed marked decreased in STEPS the week immediately post shelter-in-place, yet some recovered to near pre shelter-in-place levels. As a group, this rebound was not significant. No significant difference comparing 2019 and 2020 similar epoch STEPS data was observed for these participants.

Conclusions

The data supported the hypothesis that physical activity would be reduced in people with MS due to the COVID-19 activated shelter-in-place. Overall prolongation of reduced activity is troubling, particularly in a population where low activity is already pervasive due to detrimental secondary effects of inactivity. These observations were made possible by the use of remote activity monitoring and aligns with broader efforts to use wearables to track and promote physical activity, augment telehealth, and improve telerehabilitation across populations with chronic neurological disorders.

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Internet and Social Media Poster Presentation

LB1161 - Teleneurology for MS care at two large academic centers before and during the-COVID-19 pandemic (ID 1394)

Speakers
Presentation Number
LB1161
Presentation Topic
Internet and Social Media

Abstract

Background

Teleneurology has the potential to improve patient access to specialized multiple sclerosis (MS) centers. MS patients face multiple barriers to receiving in-clinic care including physical limitations, driving restrictions, and financial limitations. The COVID-19 pandemic further highlighted the need to re-evaluate healthcare delivery models.

Objectives

To describe the teleneurology populations at two large MS centers (Cleveland Clinic (CC) and University of California, San Francisco (UCSF)) and the changes that occurred in teleneurology use before and during the COVID-19 pandemic.

Methods

In this cross-sectional study we identified all teleneurology visits conducted at our two centers between 01-2019 and 04-2020. We compared group demographics, visit characteristics, and MS disease characteristics using T-tests and chi-squared tests for normally distributed variables and Kruskal-Wallis test for non-parametric variables.

Results

2268 patients completed 2579 teleneurology visits during the study period across the two sites (mean age 48.3±12.3 years, 72.9% female); 78.1% had an MS diagnosis. Among MS patients, age and sex were similar (p>0.1 for each) but a greater proportion of patients seen at UCSF were non-white (74.8% vs 87% white, p=<0.001), had RRMS (78.7% vs 74.5%, p=.015), were on infusible DMTs (45.5% vs 35.2%, p=<0.001), walked independently (78.4% vs 72.7% p=<0.001), and lived closer to the Center (50.0 vs 57.2 miles, p=<0.005). CC had a higher proportion of advanced practice providers (APP) conducting visits (62.3% vs 2.6%, p=<0.001) and new patient visits (15.4% vs 4.0% p=<0.001). The post-COVID population (patients seen after March 15) across both sites had a higher proportion of African Americans (12.7% vs 5.0%, p=<0.001) and shorter driving distance (35.6 vs 130 miles, p=<0.001) compared to the pre-COVID population. The populations pre- and post-COVID did not differ on sex, current DMT, disease course, or disability level.

Conclusions

Teleneurology visits at baseline reflected the organizational and teleneurology reimbursement patterns across our Centers. Following precautionary measures and expanded reimbursement for telemedicine associated with the COVID-19 pandemic, we significantly increased utilization of specialized MS teleneurology care for local and African American patients. These findings illustrate the potential for societal factors to rapidly change disparities in technology adoption and access to specialized MS care.

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Biomarkers and Bioinformatics Poster Presentation

P0063 - Development of a Custom Multivariate Proteomic Serum Based Assay for Association with Radiographic and Clinical Endpoints in MS (ID 833)

Abstract

Background

Multiple Sclerosis (MS) is a complex and heterogeneous disease. Investigating the biological pathways and cell types involved in MS pathophysiology as represented by protein biomarker expression can help inform the development of tools to monitor disease activity, disease progression, identify early evidence of relapse, and monitor treatment response.

Objectives

To develop a blood based multiplex proteomic assay that associates with clinical and radiographic endpoints in patients with MS. These endpoints include the presence of gadolinium-enhanced (Gd+) lesions, Annualized Relapse Rate (ARR) and clinically defined relapse status (active versus stable).

Methods

Serum samples (n=690 in total) from multiple deeply-phenotyped cohorts (ACP, CLIMB and EPIC) were tested in immunoassays for the measurement of 1196 proteins using Proximity Extension Assays (PEA) from OlinkTM and for 215 proteins using xMAPTM immunoassays from Myriad RBM, Inc. (RBM). Associated radiographic and clinical endpoints at the time of the blood draw were correlated with the protein levels. Twenty-one proteins were selected for inclusion in a custom assay based on their performance in univariate and multivariate statistical models, and replication across independent cohorts. Biological pathway modeling and network analysis were performed to ensure comprehensive representation of MS neurophysiology. Area under the curve (AUC) was selected as the key metric for model performance evaluation.

Results

Multivariate statistical ensembles restricted to the expression levels of the biomarkers selected for the custom assay achieved AUC performance of 0.827 for classification of the presence of Gd+ lesions, 0.802 for classification of clinically defined relapse status, and 0.930 for the classification of patients with Low ARR (≤0.2 relapses) vs High ARR (≥1.0 relapses). A multivariate model utilizing shifts in biomarker expression in longitudinally paired samples achieved the highest observed performance of 0.950 for classification of Gd+ lesion presence. In each case, the multivariate models significantly outperformed (p-value <0.05) the AUC of the highest performing univariate biomarker.

Conclusions

Multivariate models restricted to the 21 selected proteins effectively classified several radiographic and clinical endpoints with stronger performance than any single biomarker. A 21-plex custom assay panel is being developed for further investigation and validation using additional cohorts.

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Clinical Trials Poster Presentation

P0188 - A Tablet-Based Cognitive Battery to Assess Cognitive Function in People with MS: Sensitivity to Change in A Randomized Controlled Trial (ID 270)

Speakers
Presentation Number
P0188
Presentation Topic
Clinical Trials

Abstract

Background

Cognitive impairment (CI) is one of the most debilitating manifestations of multiple sclerosis (MS), and digital tools provide promising approaches to overcoming barriers to access to cognitive remediation. Developing reliable, unsupervised tools is an unmet need.

Objectives

To determine the validity and efficacy of a novel digital tool to both query cognitive impairment in MS and capture sensitivity to change after cognitive remediation.

Methods

Fifty-three participants with MS (24 with CI and 29 without CI) and 24 non-MS participants were assessed with a tablet-based cognitive battery (Adaptive Cognitive Evaluation, ACE) and standard cognitive measures: Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Associations between performance in ACE and SDMT/PASAT were explored, with group comparisons to assess if ACE modules can capture group-level differences. All 53 MS participants were then randomized to complete either a tablet-based, closed-loop digital therapeutic delivered through a video game-like interface (AKL-T03, N=27) or a control game (AKL-T09, N=26) at home for 25 minutes a day, 5 days a week, for 6 weeks. ACE assessment was repeated post-treatment. The primary outcome was performance on an attention task of ACE.

Results

Correlations between performance in SDMT/PASAT and ACE were observed (SDMT vs. ACE: R=-0.57, p<0.001; PASAT vs. ACE: R=-0.39, p=0.005). Compared to non-MS and non-CI MS participants, CI MS participants showed a slower reaction time (p=0.001) and a higher attention cost (p=0.001). Unlike the active control program, the AKL-T03 treatment program significantly improved attention task performance in MS by showing a reduced reaction time from pre- to post-treatment (p<0.001).

Conclusions

These results suggest that ACE, an adaptive, tablet-based cognitive battery, could provide reliable unsupervised cognitive assessment for people with MS. They also support our prior findings that AKL-T03 is an effective home-based cognitive remediation program for MS.

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Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0253 - Gaps in characterization of bladder dysfunction in clinical care and research (ID 1934)

Speakers
Presentation Number
P0253
Presentation Topic
Diagnostic Criteria and Differential Diagnosis

Abstract

Background

Neurogenic bladder dysfunction (BD) affects up to 90% of patients with multiple sclerosis (MS) at some point during the disease course and is a highly debilitating symptom. Despite its prevalence, there are no consensus guidelines for screening and ascertaining BD. These discrepancies could underrepresent the impact of BD on neurological decline.

Objectives

In a cohort of women with MS, we compared clinical notes and research registry scores pertaining to BD. We secondarily evaluated how often Bowel/Bladder Functional System (B/B FS) scores reflected the severity of bladder (rather than bowel) scores.

Methods

For 100 adult women with MS in the University of California, San Francisco longitudinal observational EPIC cohort (epicstudy.ucsf.edu), we retrospectively extracted data on bladder and bowel symptoms and treatments from prospectively collected clinical notes in the electronic medical record and compared them with research-grade B/B FS scores annually collected in the EPIC registry. We performed descriptive statistics to evaluate agreement between the clinical notes (BD) and research B/B FS scores at matching timepoints (within 6 months). Finally, seeking to understand whether the severity of BD could be inferred by the B/B FS, we calculated the frequency that bladder (vs. bowel) symptoms drove a higher B/B FS.

Results

We included 89 women, aged 37 to 77, with at least one matching clinical and research visit; a total of 316 visits were examined. Overall, 63 of the 89 participants (70.7%) experienced BD symptoms per clinical notes. BD symptoms were described in 284 of the 316 visits (89.9%), and research B/B FS scores were available for 283 of these. The severity of BD symptoms matched the research B/B FS in 203 (71.5%) of visits. For the rest, BD symptoms were more severe than research B/B FS for 46 visits and less severe for 34. BD severity “drove” the overall B/B FS score in 280 (98.6%); in contrast, in only 4 visits (1.4%) bowel symptoms were more severe.

Conclusions

We noted moderate discrepancy between clinical notes and research B/B FS; in 10% visits, BD symptoms were not ascertained; and in 16.3% research evaluations, BD symptoms were underscored. Inconsistencies in screening for both clinical care and research point to the need for consensus around consistency of BD symptom ascertainment and B/B FS scoring. Of relevance to interpreting B/B FS in the context of understanding the impact of BD on clinical course, B/B FS in most cases reflected the severity of bladder symptoms.

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Comorbidities Poster Presentation

P0451 - Comparing infection-related outcomes in patients with multiple sclerosis and matched controls using administrative claims data (ID 925)

Speakers
Presentation Number
P0451
Presentation Topic
Comorbidities

Abstract

Background

Few population-level risk estimates of infections in patients with multiple sclerosis (MS) exist in the United States.

Objectives

To evaluate the odds of infections associated with MS using the IQVIA™ RWD Adjudicated Claims–US database (1/1/2010–6/30/2019).

Methods

Patients with MS with ≥2 diagnoses (ICD-9-CM/ICD-10-CM: 340.xx/G35) ≥30 days apart were identified. Individuals in the non-MS cohort were required to have 2 diagnoses for any condition. A randomly selected index office visit date meeting the following criteria was selected: index age 18-64, continuous 12-month eligibility pre/post, no pregnancy claims, no antibiotic/antiviral claim 60 days prior, no inpatient residential care/end-stage renal disease facility, and no HIV/HCV. Patients with and without MS were matched 1:1 on age, sex, payer type, Census region, and index year. Infections were defined as likelihood of presence of antibiotics/antivirals claims and inpatient hospitalizations in the 12-month post-index period. Multivariable logistic regression models were used to measure the association of MS diagnosis with presence of antibiotic/antiviral claims and inpatient hospitalizations for infections. Explanatory variables were: age group, sex, payer type, region, index year (2011-2018), and select comorbidities.

Results

A total of 87,755 patients with MS met study inclusion criteria and were matched to 87,755 patients without MS. Mean (SD) age was 47.3 (10.5) years, 75.7% were female, 65.7% had commercial insurance, and 34.3% had self-insured employer insurance. Patients were from the South (32.7%), Midwest (31.3%), Northeast (25.5%) or West (10.5%) regions. Most common outpatient diagnoses of infections in both cohorts were urinary tract infection, acute sinusitis, acute upper respiratory tract infections, acute pharyngitis, and mycoses. A greater proportion of patients with MS vs. without MS had presence of antibiotic/antiviral claims (53.8% vs. 48.2%; p<0.0001) and inpatient hospitalization for infections (3.2% vs. 1.3%; p<0.0001). Compared with the non-MS cohort, patients with MS had significantly higher odds of an antibiotic/antiviral claim (adjusted odds ratio [AOR], 95% confidence interval [CI]: 1.18 [1.16, 1.20]) and significantly higher odds of inpatient hospitalization (AOR, 95% CI: 2.00 [1.86, 2.15]).

Conclusions

These findings highlight the increased odds of infection among the commercially and self-insured patients with MS in the US.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1005 - An electronic, unsupervised Patient Reported Expanded Disability Status Scale for Multiple Sclerosis (ID 1921)

Speakers
Presentation Number
P1005
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

In persons with multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) is the criterion standard for assessing disability, but its in-person nature constrains patient participation in research and clinical assessments.

Objectives

To develop and validate a scalable, electronic, unsupervised patient-reported EDSS (ePR-EDSS) that would capture MS-related disability across the spectrum of severity.

Methods

We enrolled 136 adult MS patients, split into a preliminary testing Cohort 1 (n=50), and a validation Cohort 2 (n=86), which was evenly distributed across EDSS groups. Each patient completed an ePR-EDSS either immediately before or after a MS clinician’s Neurostatus EDSS (NS-EDSS) evaluation. The final ePR-EDSS version includes 23 questions, takes between 7-12 minutes to complete (based on time measured for Cohort 2 participants), and can be accessed at https://openmsbioscreen.ucsf.edu/predss/about.

Results

In Cohort 2, mean age was 50.6 years (range 26-80) and median EDSS was 3.5 (IQR 1.5, 5.5). The ePR-EDSS and EDSS agreed within 1-point for 86% of examinations; kappa for agreement within 1-point was 0.85 (p<0.001). The correlation coefficient between the two measures was 0.91 (<0.001). For individual functional systems, complete agreement was highest for the brainstem score (55.8%) and lowest for the sensory score (31.4%). In sensitivity analyses adjusted for NS-EDSS, the absolute difference between ePR-EDSS and NS-EDSS was not significantly related to age, sex, disease duration, years of education, or the timepoint at which the ePR-EDSS tool was assessed (before/after neurological exam).

Conclusions

The ePR-EDSS is unique compared to other published tools - it can be accessed and performed by the patient without any supervision, is freely and openly available, has built-in logic to calculate functional system and total scores, and is validated over a wide NS-EDSS range. It demonstrated high correlation with NS-EDSS, with good agreement even at lower EDSS levels. For clinical care, the ePR-EDSS could enable the longitudinal monitoring of a patient’s disability. For research, it provides a valid and rapid measure across the entire spectrum of disability and permits broader participation with fewer in-person assessments.

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Symptom Management Poster Presentation

P1107 - Proactively evaluating and treating changes in function in people with multiple sclerosis: the CoachMS pilot study (ID 1488)

Speakers
Presentation Number
P1107
Presentation Topic
Symptom Management

Abstract

Background

In current disease management models for multiple sclerosis (MS), symptoms are treated separately, by multiple specialists, despite the fact that many symptoms interact and exacerbate one another. Impairments in bladder function, ambulation, and mood (BAM) are a common and often debilitating triad of symptoms with compounded detrimental effect.

Objectives

Assess the feasibility of CoachMS: a novel closed-loop, remote, interdisciplinary symptom management platform that integrates specific behavioral approaches to encourage patient self-management.

Methods

We enrolled 21 participants from the University of California, San Francisco MS Center with clinician- or self-reported symptoms in at least 2 of the 3 BAM domains. To quantitatively measure BAM symptoms, participants were given a Fitbit Flex2 to wear for the duration of the study and assessed with weekly, online surveys. At 2 weeks, together with the study team, individual goals were set for each participant. A simple 1:1 randomization allocated participants to either Coach or control groups. The CoachMS group received targeted interventions throughout the remainder of the study if they failed to meet their individual BAM goals, or displayed worsening. The control group was monitored without intervention. Our primary outcome was feasibility; secondary outcomes included proportion of recommended treatments pursued, and changes in BAM symptom severity.

Results

12 participants (55%) completed the study. These participants demonstrated excellent adherence to study protocol and reported satisfaction with the pilot platform. Coach participants demonstrated greater follow-through with clinical recommendations from the 2-week goal setting stage than controls (OR 9.33, 95% CI (0.89, 97.62)). As a cohort, a trend towards improvement in each BAM symptom was noted although the CoachMS and control groups did not differ. One control participant, reporting suicidality in the weekly questionnaires but not to her primary clinicians, was urgently evaluated per protocol, and hospitalized.

Conclusions

The CoachMS platform, a closed-loop system for managing MS symptoms, was feasible; retention can be further optimized with lower questionnaire burden. Reminders and contact from study team improved recommendation follow-though in the Coach group, particularly for outside referrals. The CoachMS protocol could represent a viable, accessible and cost-effective tool to monitor and treat MS symptoms in near real-time; a larger trial is planned.

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Symptom Management Poster Presentation

P1113 - Underutilization of Physical Therapy Resources for Symptomatic Women with MS During and Following Pregnancy (ID 1240)

Speakers
Presentation Number
P1113
Presentation Topic
Symptom Management

Abstract

Background

Patients with MS continue to have symptoms of their disease even when inflammatory activity is reduced by DMTs. Although this activity is reduced during pregnancy - especially in the third trimester – women with MS can experience ongoing symptoms during pregnancy, or new ones in the immediate post-partum period, that degrade quality of life. Many MS-related and postpartum symptoms can be improved with physical therapy (PT), but there are no guidelines on pregnancy-related rehabilitation in MS.

Objectives

To evaluate the prevalence of PT-amenable symptoms and patterns of PT referrals in a cohort of UCSF MS Clinic patients who became pregnant.

Methods

Data collected prospectively between 09-2005 to 08-2019 were retrospectively extracted from electronic medical records (EMR) for the year before conception, during pregnancy, and year postpartum. This included clinical visits, MS therapies and symptoms (as defined by the National MS Society). PT and pelvic floor PT orders and notes were also extracted.

Results

We included 142 live birth pregnancies from 118 women. During the course of their pregnancy and within the year postpartum, 107 women (75.4%) reported at least one PT-amenable symptom. A total of 30 (28.0%) referrals were made to PT, with attendance confirmed for 10 (33.3%). Symptoms most commonly triggering a referral for PT evaluation were numbness and urinary incontinence. Falls were reported after 10 of the pregnancies; 4 resulted in a referral to PT. Forty-one women reported urinary incontinence: 11 (26.8%) were referred to PT, and 2 to pelvic floor PT. Nineteen women experienced a documented relapse during pregnancy and/or postpartum: 11 received a PT referral, and 4 attended PT.

Conclusions

While women with MS recorded at least 1 PT-amenable during or following 75.4% of their pregnancies, only 28% of these were referred to PT – and only a third attended PT. Of significance was the 4.9% referral rate for pelvic floor PT in postpartum women with a record of urinary incontinence. Pelvic floor PT is a mainstay of general postpartum care in many European countries. These data illustrate critical gaps in rehabilitation referral, access and use at the intersection of neurological conditions and pregnancy in a large US-based MS clinic. They lend support for quality improvement efforts to improve care pathways and for telerehabilitation innovations to reduce barriers to access and improve synergistic care between PT, MD and urologic care.

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Reproductive Aspects and Pregnancy Poster Presentation

P1117 - Clinical and radiologic disease activity in pregnancy and postpartum in multiple sclerosis  (ID 1930)

Speakers
Presentation Number
P1117
Presentation Topic
Reproductive Aspects and Pregnancy

Abstract

Background

Multiple sclerosis (MS) typically begins between the ages of 20 to 40 years and has a female to male ratio of 3:1. As such, MS is primarily diagnosed in women of reproductive age. Several studies have demonstrated that women experience fewer MS relapses during the immunotolerant state of pregnancy; however, an increase in relapses has been observed postpartum. As clinical inflammatory activity postpartum could be confused with other common neurological conditions, magnetic resonance imaging (MRI) detects new inflammatory lesions objectively. No large case series of MRI-defined postpartum inflammatory activity have been published, to our knowledge.

Objectives

To evaluate clinical and radiological inflammatory activity in women with multiple sclerosis during pregnancy and postpartum.

Methods

We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the UCSF Multiple Sclerosis Center between 2005 and 2018. Annualized relapse rate (ARR) and proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions were compared before, during and after pregnancy.

Results

We identified 155 pregnancies in 119 women (median EDSS 2.0). For the 146 live birth pregnancies, pre-pregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p=0.017) and increased in the three months postpartum (ARR 0.61, p=0.012); 16.5% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 52.5% had new T2 and/or Gd+ lesions postpartum compared to 32.2% pre-pregnancy (P=0.023). Postpartum clinical relapses were associated with Gd+ lesions (p<0.0001). However, for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 30.9%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio (OR)=0.20, 95% CI 0.047-0.82) and early initiation of MS therapy (OR=0.28, 0.080-0.98) were observed for relapses.

Conclusions

We confirm prior reports of decreased relapse rate during pregnancy and increased rate in the three months postpartum. We report a significant association between this clinical activity and inflammation on MRI, as well as postpartum radiologic activity even in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

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Reproductive Aspects and Pregnancy Poster Presentation

P1132 - Pregnancy outcomes in patients treated with ocrelizumab (ID 957)

Speakers
Presentation Number
P1132
Presentation Topic
Reproductive Aspects and Pregnancy

Abstract

Background

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for the treatment of relapsing and primary progressive multiple sclerosis (MS). As many MS patients are women of reproductive age, pregnancy outcomes in OCR-exposed patients are of relevance.

Objectives

To report an update on pregnancy outcomes in women with MS receiving OCR in clinical trials and post-marketing.

Methods

Analysis includes pregnancies in women receiving OCR in clinical trials/post-marketing (global safety database). Women of childbearing potential should use contraception while on treatment and for 6 or 12 months after the last OCR infusion, depending on local regulations. Based on the average terminal half-life of 26 days and the lack of relevant placental transfer in the 1st trimester, a fetus was considered to have fetal OCR exposure if the last infusion occurred within 3 months of conception, during pregnancy, or if the date was unknown.

Results

As of March 27, 2020, 726 total pregnancies exposed to OCR in women with MS (n=608) or unknown indication (n=118) were reported. Of the 608 MS pregnancies, 234 were considered to have fetal OCR exposure, 102 were not, and 272 had unknown exposure. Preliminary outcomes of total MS pregnancies (n/%) were: 156/64.2% live births, 37/15.2% elective/therapeutic abortions, 42/17.3% spontaneous abortions, 3/1.2% stillbirths, 5/2.1% ectopic pregnancies; 134 pregnancies were ongoing, 80 lost to follow-up (FU) and 151 had unknown/not reported (NR) outcomes. Of the 156 total live births, 6 congenital malformations were reported. Preliminary outcomes of MS pregnancies with fetal OCR exposure (n/%) were: 62/59.6% live births, 24/23.1% elective/therapeutic abortions, 15/14.4% spontaneous abortions, 2/1.9% stillbirths, 1/1.0% ectopic pregnancies; 55 pregnancies were ongoing, 37 lost to FU and 38 had unknown/NR outcomes. Infant health questionnaires were received from 13 live births with up to 1-year FU and will continue to be collected, including data on vaccinations and infections: 9 infants had no infections and 1 had a resolved infection.

Conclusions

Cases reviewed to date do not suggest an increased risk of adverse pregnancy outcomes (including spontaneous abortions or malformations) with OCR use, whether or not fetal exposure occurred or was unknown. The updated outcomes remain in line with prior reports and within the expected epidemiologic range. Data continue to be collected and assessed as per post-authorization commitments.

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Reproductive Aspects and Pregnancy Poster Presentation

P1135 - Risk factors for peripartum depression in women with multiple sclerosis (ID 1419)

Speakers
Presentation Number
P1135
Presentation Topic
Reproductive Aspects and Pregnancy

Abstract

Background

Peripartum depression (PPD), i.e. depression in late pregnancy to 1 year postpartum, occurs in 7-19% of women. There are limited data on PPD in multiple sclerosis (MS).

Objectives

To evaluate the prevalence of PPD in women with MS, and to evaluate risk factors for PPD in MS, both factors associated with PPD in the general population, as well as disease-related factors.

Methods

We performed retrospective analysis of prospectively collected clinical data. Women with MS followed at UCSF MS Center who became pregnant from 2015-2018 were identified in the electronic medical record. The primary outcome was PPD determined by clinical record review. Prevalence of PPD was estimated with logistic regression with generalized estimating equations (GEE), accounting for women with multiple pregnancies. Univariable analyses with GEE logistic regression evaluated predictors of PPD (age, marital status, parity, delivery season, prematurity, birth weight, delivery mode, premorbid depression/anxiety, antidepressant discontinuation, sleep disturbance, breastfeeding). Factors significant in univariable analyses were included in multivariable analysis. GEE logistic regression evaluated association between inflammatory disease activity (relapses in pregnancy/postpartum; gadolinium enhancing lesions postpartum), disease severity (Expanded Disability Status Scale, EDSS) and PPD.

Results

We identified 143 pregnancies (age 33.1+/-4.7 years; 93% relapsing remitting MS, 7% clinically isolated syndrome; 45% premorbid depression) in 111 women who had live birth outcomes and known PPD status. PPD was present in 12.6% (95% CI 7.3-17.8) of pregnancies. In univariable analyses, statistically significant factors associated with PPD included older age (OR 1.16, 95% CI 1.03-1.32 for 1-year increase), primiparity (OR 4.02, 95% CI 1.14-14.23), premorbid depression (OR 3.70, 95% CI 1.27-10.01), postpartum sleep disturbance (OR 3.23, 95% CI 1.17-8.91) and breastfeeding difficulty (OR 3.58, 95% CI 1.27-10.08). Maternal age (OR 1.17, 95% CI 1.02-1.34), primiparity (OR 8.10, 95% CI 1.38-47.40) and premorbid depression (OR 3.89, 95% CI 1.04-14.60) remained associated with PPD in multivariable analyses. Relapses, MRI activity and EDSS were not associated with PPD.

Conclusions

PPD in MS was similar to the general population, but was likely underestimated due to lack of standardized screening. PPD could influence maternal self-management of MS. Prospective evaluation with screening for PPD is needed.

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Presenter Of 2 Presentations

Comorbidities Poster Presentation

P0451 - Comparing infection-related outcomes in patients with multiple sclerosis and matched controls using administrative claims data (ID 925)

Speakers
Presentation Number
P0451
Presentation Topic
Comorbidities

Abstract

Background

Few population-level risk estimates of infections in patients with multiple sclerosis (MS) exist in the United States.

Objectives

To evaluate the odds of infections associated with MS using the IQVIA™ RWD Adjudicated Claims–US database (1/1/2010–6/30/2019).

Methods

Patients with MS with ≥2 diagnoses (ICD-9-CM/ICD-10-CM: 340.xx/G35) ≥30 days apart were identified. Individuals in the non-MS cohort were required to have 2 diagnoses for any condition. A randomly selected index office visit date meeting the following criteria was selected: index age 18-64, continuous 12-month eligibility pre/post, no pregnancy claims, no antibiotic/antiviral claim 60 days prior, no inpatient residential care/end-stage renal disease facility, and no HIV/HCV. Patients with and without MS were matched 1:1 on age, sex, payer type, Census region, and index year. Infections were defined as likelihood of presence of antibiotics/antivirals claims and inpatient hospitalizations in the 12-month post-index period. Multivariable logistic regression models were used to measure the association of MS diagnosis with presence of antibiotic/antiviral claims and inpatient hospitalizations for infections. Explanatory variables were: age group, sex, payer type, region, index year (2011-2018), and select comorbidities.

Results

A total of 87,755 patients with MS met study inclusion criteria and were matched to 87,755 patients without MS. Mean (SD) age was 47.3 (10.5) years, 75.7% were female, 65.7% had commercial insurance, and 34.3% had self-insured employer insurance. Patients were from the South (32.7%), Midwest (31.3%), Northeast (25.5%) or West (10.5%) regions. Most common outpatient diagnoses of infections in both cohorts were urinary tract infection, acute sinusitis, acute upper respiratory tract infections, acute pharyngitis, and mycoses. A greater proportion of patients with MS vs. without MS had presence of antibiotic/antiviral claims (53.8% vs. 48.2%; p<0.0001) and inpatient hospitalization for infections (3.2% vs. 1.3%; p<0.0001). Compared with the non-MS cohort, patients with MS had significantly higher odds of an antibiotic/antiviral claim (adjusted odds ratio [AOR], 95% confidence interval [CI]: 1.18 [1.16, 1.20]) and significantly higher odds of inpatient hospitalization (AOR, 95% CI: 2.00 [1.86, 2.15]).

Conclusions

These findings highlight the increased odds of infection among the commercially and self-insured patients with MS in the US.

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Reproductive Aspects and Pregnancy Poster Presentation

P1132 - Pregnancy outcomes in patients treated with ocrelizumab (ID 957)

Speakers
Presentation Number
P1132
Presentation Topic
Reproductive Aspects and Pregnancy

Abstract

Background

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for the treatment of relapsing and primary progressive multiple sclerosis (MS). As many MS patients are women of reproductive age, pregnancy outcomes in OCR-exposed patients are of relevance.

Objectives

To report an update on pregnancy outcomes in women with MS receiving OCR in clinical trials and post-marketing.

Methods

Analysis includes pregnancies in women receiving OCR in clinical trials/post-marketing (global safety database). Women of childbearing potential should use contraception while on treatment and for 6 or 12 months after the last OCR infusion, depending on local regulations. Based on the average terminal half-life of 26 days and the lack of relevant placental transfer in the 1st trimester, a fetus was considered to have fetal OCR exposure if the last infusion occurred within 3 months of conception, during pregnancy, or if the date was unknown.

Results

As of March 27, 2020, 726 total pregnancies exposed to OCR in women with MS (n=608) or unknown indication (n=118) were reported. Of the 608 MS pregnancies, 234 were considered to have fetal OCR exposure, 102 were not, and 272 had unknown exposure. Preliminary outcomes of total MS pregnancies (n/%) were: 156/64.2% live births, 37/15.2% elective/therapeutic abortions, 42/17.3% spontaneous abortions, 3/1.2% stillbirths, 5/2.1% ectopic pregnancies; 134 pregnancies were ongoing, 80 lost to follow-up (FU) and 151 had unknown/not reported (NR) outcomes. Of the 156 total live births, 6 congenital malformations were reported. Preliminary outcomes of MS pregnancies with fetal OCR exposure (n/%) were: 62/59.6% live births, 24/23.1% elective/therapeutic abortions, 15/14.4% spontaneous abortions, 2/1.9% stillbirths, 1/1.0% ectopic pregnancies; 55 pregnancies were ongoing, 37 lost to FU and 38 had unknown/NR outcomes. Infant health questionnaires were received from 13 live births with up to 1-year FU and will continue to be collected, including data on vaccinations and infections: 9 infants had no infections and 1 had a resolved infection.

Conclusions

Cases reviewed to date do not suggest an increased risk of adverse pregnancy outcomes (including spontaneous abortions or malformations) with OCR use, whether or not fetal exposure occurred or was unknown. The updated outcomes remain in line with prior reports and within the expected epidemiologic range. Data continue to be collected and assessed as per post-authorization commitments.

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