Author Of 6 Presentations
LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)
- C. Chien
- H. Zimmermann
- S. Specovius
- F. Oertel
- D. Bichuetti
- M. Idagawa
- A. Altintas
- U. Tanriverdi
- S. Siritho
- L. Pandit
- A. D'Cunha
- M. Sá
- R. Figueiredo
- C. Tongco
- P. Qian
- I. Lotan
- V. Khasminsky
- M. Hellmann
- H. Stiebel-Kalish
- D. Rotstein
- L. Waxman
- D. Ontaneda
- K. Nakamura
- H. Abboud
- M. Subei
- Y. Mao-Draayer
- J. Havla
- N. Asgari
- I. Kister
- Z. Rimler
- A. Reid
- M. Ringelstein
- S. Broadley
- S. Arnett
- B. Marron
- A. Jolley
- M. Wunderlich
- S. Green
- L. Cook
- M. Yeaman
- T. Smith
- A. Brandt
- P. Skejø
- V. Cruz Silva
- J. Wuerfel
- F. Paul
- G. International Clinical Consortium For Nmosd
Abstract
Background
Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).
Objectives
The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.
Methods
For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.
Results
Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.
Conclusions
We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.
LB1262 - Low Prevalence of SARS-CoV-2 Antibodies in People with Multiple Sclerosis Residing in Massachusetts (ID 2159)
- E. Klawiter
- J. Smith
- K. Brewer
- K. Stockel
- S. Fischinger
- C. Luedemann
- H. Bien
- A. Russo
- A. Vaeth
- R. Bakshi
- S. Bhattacharyya
- A. Cabot
- I. George
- R. Gillani
- M. Hickey
- M. Houtchens
- T. Bockow Kaplan
- D. Kimbrough
- I. Kister
- F. Mateen
- M. Matiello
- C. Severson
- T. Singhal
- J. Stankiewicz
- L. Stazzone
- H. Weiner
- J. Zurawski
- A. Eloyan
- T. Chitnis
- G. Alter
Abstract
Background
Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2. Most people with multiple sclerosis (MS) are treated with immunomodulators or immunosuppressants, so it is crucial to understand the immune response to the novel SARS-CoV-2 in people with MS.
Objectives
To investigate the prevalence and persistence of the SARS-CoV-2 antibody response in MS and how this relates to MS phenotype and treatment.
Methods
227 consecutive people with MS residing in MA and receiving care at Massachusetts General Hospital or Brigham and Women’s Hospital and 143 of their cohabitants were enrolled May 29-July 23, 2020. In addition, 8 people with MS receiving care elsewhere who tested positive for SARS-CoV-2 nasal swab PCR and 7 cohabitants of that group were enrolled to enrich the sample for select analyses. Each participant remotely submitted a dried blood card for in-house MGH SARS-CoV-2 IgG ELISA assay testing. The assay displays 99.7% sensitivity and 100% specificity >14 days from symptom onset. Participants completed a REDCap questionnaire covering demographics, MS history and treatments, comorbidities, and COVID-19 symptoms and exposure. Antibody prevalence in MS participants will be compared to that in their cohabitants using Pearson’s Chi-squared tests.
Results
The majority of MS participants were characterized as relapsing/remitting (76.8%) and were taking disease modifying therapies (72.6%) at the time of collection. SARS-CoV-2 antibodies were detected in 3.5% of people with MS residing in MA and 6.3% of their cohabitants (X2=1.54, p=0.22). For comparison, ~1.5% of the MA population had tested positive by PCR in this date range. Exposure and treatment data will be presented in 13 cases of antibody discordance between the person with MS and his/her cohabitant; the person with MS was antibody-negative in 10 cases and antibody-positive in 3 cases with discordance. In total there were 6 MS participants and no cohabitants who previously tested positive by nasal swab PCR but lacked antibodies at follow-up. Of the COVID-positive participants (by PCR or antibody), 54.5% (6 of 11) of MS and 88.9% (8 of 9) of cohabitants were asymptomatic (p=0.16).
Conclusions
Antibody prevalence was low overall in people with MS residing in MA. Discordance between MS participants and their cohabitants and lack of detectable antibodies in some people with MS with prior nasal swab PCR positivity suggest SARS-CoV-2 antibodies may be less persistent in people with MS.
P0018 - Variability of the response to immunotherapy among sub-groups of patients with multiple sclerosis (ID 1239)
- I. Diouf
- C. Malpas
- D. Horakova
- E. Kubala Havrdová
- F. Patti
- V. Shaygannejad
- S. Ozakbas
- G. Izquierdo
- S. Eichau
- M. Zakaria
- M. Onofrj
- A. Lugaresi
- R. Alroughani
- A. Prat
- M. Girard
- P. Duquette
- M. Terzi
- C. Boz
- F. Grand'Maison
- S. Hamdy
- P. Sola
- D. Ferraro
- P. Grammond
- R. Turkoglu
- H. Butzkueven
- B. Yamout
- A. Altintas
- V. Van Pesch
- D. Maimone
- J. Lechner-Scott
- R. Bergamaschi
- R. Karabudak
- F. Giuliano
- C. McGuigan
- E. Cartechini
- M. Barnett
- S. Hughes
- M. Sa
- L. Kappos
- C. Ramo-Tello
- E. Cristiano
- S. Hodgkinson
- D. Spitaleri
- A. Soysal
- T. Petersen
- M. Slee
- E. Butler
- F. Granella
- F. Verheul
- P. McCombe
- R. Ampapa
- O. Skibina
- J. Prevost
- L. Sinnige
- J. Sánchez-Menoyo
- S. Vucic
- G. Laureys
- L. Van Hijfte
- D. Khurana
- R. Macdonell
- T. Castillo-Trivino
- O. Gray
- E. Agüera
- I. Kister
- C. Shaw
- N. Deri
- T. Al-Harbi
- Y. Fragoso
- T. Csepany
- A. Sempere
- T. Kalincik
Abstract
Background
Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited.
Objectives
To assess whether patients’ response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype.
Methods
Using the international MSBase registry, we selected patients with MS followed for ≥1 year, with ≥3 visits, ≥1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity.
Results
Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively].
Conclusions
DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. In general, the effectiveness of DMTs was most pronounced in subgroups with shorter MS duration, lower EDSS, lower relapse rate and relapsing MS phenotype.
P0244 - A simple two-step test based on CSF flow cytometry helps to discriminate MS from other inflammatory and non-inflammatory neurologic disorders (ID 1943)
Abstract
Background
Several studies have shown that relative proportions of B-lineage cells are increased in CSF of patients with MS as compared to other inflammatory (OIND) and non-inflammatory (NIND) neurologic disorders. We hypothesized that the relative proportion of CD19+ and plasma (CD19+138+) cells in CSF, as assessed with commercially available flow cytometry, could be useful for improving the specificity of MS diagnostics.
Objectives
1. To determine whether a combination of elevated CD19+ cells and plasma (CD19+138+) cells in CSF (‘CD19/Plasma Cell Test’) allows for accurate differentiation of MS from OIND (e.g. MOG Ab disorder, neurosarcoidosis, Susac syndrome) and between MS and NIND (e.g. stoke, malignancies, conversion disorder). 2. To compare the sensitivity and specificity of CD19/Plasma Cell Test to that of oligoclonal bands (OCB) in CSF.
Methods
We retrospectively reviewed the charts of consecutive patients evaluated at NYU Langone Medical Center between 1/2013 - 3/2020 for whom lymphocyte subtyping in CSF was available. We defined ‘elevated CD19 count’ as >1% of total lymphocyte count in CSF and ‘elevated plasma cell count’ as >0.1% of total lymphocyte count in CSF. We calculated proportions of patients with elevated CD19 and, within this subset, of patients with elevated plasma cell counts for MS, OIND, and NIND. We calculated the sensitivity and specificity of the CD19/Plasma Cell Test for discriminating MS from OIND and from NIND.
Results
The cohort was comprised of 69 patients with MS (age at LP: 39.1 ±11.7 years; 64% female, 65% white), 25 with OIND (age - 45.3±13.7; 56% female; 48% white), and 43 with NIND (age - 48.5 ±14.8; 63% female; 70% white). OCB (2 or more) were present in 51/67 MS patients (76%), 10/13 IND (77%) and 0/38 NIND (0%). Thus, OCB had sensitivity 76% for MS, and specificity of 56% for MS when compared to OIND, and 100% when compared to NIND. Elevated CD19 count was found in 45/69 MS patients (65%), 10/25 OIND (40%), and 8/43 of NIND (18%). Of the patients with elevated CD19 count (N=63), 27 MS patients, 3 OIND and 0 NIND patients had an elevated plasma cell count. Thus, a two step-test that sequentially assesses for elevated CD19 count and elevated plasma cell count, has sensitivity of 39% for MS, specificity of 88% for discriminated MS from OIND, and 100% for discriminating MS from NIND.
Conclusions
OCB have high sensitivity for MS, but lack specificity for discriminating MS from OIND. A simple, two-step CD19/Plasma Cell Test, based on widely available flow cytometry assay, was inferior to OCB with regard to sensitivity for MS (39% v. 76%), but superior with regard to specificity (88% v 56%) for discriminating MS from OIND. Both tests had excellent specificity for differentiating MS from NIND.
P0300 - Baseline features in DISCOntinuation of disease modifying therapies in Multiple Sclerosis (DISCOMS) (ID 791)
Abstract
Background
New relapses and magnetic resonance imaging (MRI) abnormalities diminish as people age with multiple sclerosis (MS). Data supporting use of disease modifying therapies (DMTs), from studies with typical inclusion ages of 18-55, suggest diminished benefit in older compared with younger individuals. Whether it is beneficial to continue, or safe to discontinue, DMTs as people age beyond 55 remains unknown. Retrospective studies show those at greatest risk of new inflammatory disease activity upon DMT discontinuation are younger and had recent new relapse and/or MRI scan activity.
Objectives
Present the design and baseline data in our study evaluating whether older individuals with MS who discontinue their DMT have no worse risk of new disease activity compared to those who remain on DMT.
Methods
This is a randomized (1:1), controlled, rater-blinded study in which 260 MS participants aged 55 and older and continuously taking DMTs (at least 5 years, minimum 2 years on current DMT) were enrolled at 19 sites in the United States. They have no evidence of MS relapse for 5+ years or new MRI lesion for 3+ years, and will be followed for up to 2 years, with study visits every 6 months. Primary outcome is either a new MS relapse or T2 brain MRI lesion. Secondary outcomes are 6-month confirmed increase in Extended Disability Status Scores (EDSS), and worsening of Symbol Digit Modality Test or patient-reported outcomes.
Results
Mean age of participants is 63 ± 5 years, and 83.7% are female. Racial/ethnic breakdown is 89.2% White, 9.2% Black or African American, 0.8% Hispanic/Latino, and 0.8% Other. Participants average 22.3 ± 10.5 years since symptom onset, and 13.5 ± 7 years since last relapse. Most have Relapsing-Remitting MS (83.7%), with 13.1% Secondary Progressive and 3.2% Primary Progressive MS. At enrollment, 42.6% were on an interferon, 30.3% on glatiramer acetate, 15.1% dimethyl fumarate, 6.4% fingolimod, 3.2% teriflunomide, 1.6% natalizumab, and 0.8% ocrelizumab. EDSS scores average 3.3 ± 1.8, and 77.8% of participants rate their treatment satisfaction as Satisfied or Very Satisfied at enrollment.
Conclusions
The DISCOMS study is the first controlled trial to address whether it is safe to discontinue DMTs in MS. Enrolled participants represent a unique cohort of stable, older MS patients with relatively low disability. Upon completion, the study will increase our understanding of the utility of MS DMTs throughout the lifespan of MS.
P1039 - Improvements in patient-reported SymptoMScreen scores among ocrelizumab-treated patients with RRMS: 2-year results from the CASTING clinical trial (ID 977)
Abstract
Background
SymptoMScreen is a patient-reported outcome tool designed to rapidly assess symptom limitations across 12 symptoms commonly affected in people with multiple sclerosis (MS). Each domain is scored on a 7-point Likert scale (0 [not affected] to 6 [total limitation]) and domain scores are summed to calculate a total score ranging from 0 to 72. SymptoMScreen is used in the ongoing, open-label, single-arm, Phase IIIb CASTING clinical trial (NCT02861014).
Objectives
To report 2-year changes in SymptoMScreen scores among patients with relapsing-remitting MS (RRMS) from CASTING.
Methods
In CASTING, patients with RRMS (Expanded Disability Status Scale [EDSS] score ≤4.0 at screening; disease duration ≤10 years) and a prior suboptimal response to ≥6 months of treatment with one or two disease-modifying therapies (DMTs; including orals and injectables) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. SymptoMScreen was performed at baseline, Week 48 (1-year interim data) and Week 96 (2-year final data).
Results
A total of 680 patients (female, 64%; mean [SD] baseline EDSS score, 2.1 [1.1]) who were previously treated with one (n=414 [60.4%]) or two (n=269 [39.6%]) DMTs were enrolled (most frequently for MRI with relapse activity [40.4%]) and evaluated in the intent-to-treat population; 644 patients completed treatment. Total SymptoMScreen mean (SD) score reflected mild symptom burden at baseline (15.19 [12.67]) and improved significantly through Year 2 (13.62 [12.51]; p<0.001 [p values were not adjusted for multiplicity]). Statistically significant improvements after 2 years were observed for sensory symptoms (Δ-0.28; p<0.001), fatigue (Δ-0.23; p<0.001), vision (Δ-0.21; p<0.001), depression (Δ-0.15; p<0.01) and dizziness (Δ-0.14; p<0.01) domains. Non-significant improvements in symptom burden after 2 years (p>0.05) were observed in walking (Δ-0.1), cognition (Δ-0.10), anxiety (Δ-0.07), bodily pain (Δ-0.05), hand function (Δ-0.03) and bladder control (Δ-0.01), while a non-significant worsening was observed in the spasticity domain (Δ+0.04). The proportion of patients with at least one symptom causing at least moderate limitation (domain score ≥4) decreased from 31.6% at baseline to 26.3% at Year 2.
Conclusions
Patients with RRMS and a suboptimal response to therapy who switched to ocrelizumab experienced an improvement in symptom burden in the majority of SymptoMScreen domains after 2 years, which was most pronounced in sensory, fatigue and vision.
Presenter Of 2 Presentations
P0244 - A simple two-step test based on CSF flow cytometry helps to discriminate MS from other inflammatory and non-inflammatory neurologic disorders (ID 1943)
Abstract
Background
Several studies have shown that relative proportions of B-lineage cells are increased in CSF of patients with MS as compared to other inflammatory (OIND) and non-inflammatory (NIND) neurologic disorders. We hypothesized that the relative proportion of CD19+ and plasma (CD19+138+) cells in CSF, as assessed with commercially available flow cytometry, could be useful for improving the specificity of MS diagnostics.
Objectives
1. To determine whether a combination of elevated CD19+ cells and plasma (CD19+138+) cells in CSF (‘CD19/Plasma Cell Test’) allows for accurate differentiation of MS from OIND (e.g. MOG Ab disorder, neurosarcoidosis, Susac syndrome) and between MS and NIND (e.g. stoke, malignancies, conversion disorder). 2. To compare the sensitivity and specificity of CD19/Plasma Cell Test to that of oligoclonal bands (OCB) in CSF.
Methods
We retrospectively reviewed the charts of consecutive patients evaluated at NYU Langone Medical Center between 1/2013 - 3/2020 for whom lymphocyte subtyping in CSF was available. We defined ‘elevated CD19 count’ as >1% of total lymphocyte count in CSF and ‘elevated plasma cell count’ as >0.1% of total lymphocyte count in CSF. We calculated proportions of patients with elevated CD19 and, within this subset, of patients with elevated plasma cell counts for MS, OIND, and NIND. We calculated the sensitivity and specificity of the CD19/Plasma Cell Test for discriminating MS from OIND and from NIND.
Results
The cohort was comprised of 69 patients with MS (age at LP: 39.1 ±11.7 years; 64% female, 65% white), 25 with OIND (age - 45.3±13.7; 56% female; 48% white), and 43 with NIND (age - 48.5 ±14.8; 63% female; 70% white). OCB (2 or more) were present in 51/67 MS patients (76%), 10/13 IND (77%) and 0/38 NIND (0%). Thus, OCB had sensitivity 76% for MS, and specificity of 56% for MS when compared to OIND, and 100% when compared to NIND. Elevated CD19 count was found in 45/69 MS patients (65%), 10/25 OIND (40%), and 8/43 of NIND (18%). Of the patients with elevated CD19 count (N=63), 27 MS patients, 3 OIND and 0 NIND patients had an elevated plasma cell count. Thus, a two step-test that sequentially assesses for elevated CD19 count and elevated plasma cell count, has sensitivity of 39% for MS, specificity of 88% for discriminated MS from OIND, and 100% for discriminating MS from NIND.
Conclusions
OCB have high sensitivity for MS, but lack specificity for discriminating MS from OIND. A simple, two-step CD19/Plasma Cell Test, based on widely available flow cytometry assay, was inferior to OCB with regard to sensitivity for MS (39% v. 76%), but superior with regard to specificity (88% v 56%) for discriminating MS from OIND. Both tests had excellent specificity for differentiating MS from NIND.
P1039 - Improvements in patient-reported SymptoMScreen scores among ocrelizumab-treated patients with RRMS: 2-year results from the CASTING clinical trial (ID 977)
Abstract
Background
SymptoMScreen is a patient-reported outcome tool designed to rapidly assess symptom limitations across 12 symptoms commonly affected in people with multiple sclerosis (MS). Each domain is scored on a 7-point Likert scale (0 [not affected] to 6 [total limitation]) and domain scores are summed to calculate a total score ranging from 0 to 72. SymptoMScreen is used in the ongoing, open-label, single-arm, Phase IIIb CASTING clinical trial (NCT02861014).
Objectives
To report 2-year changes in SymptoMScreen scores among patients with relapsing-remitting MS (RRMS) from CASTING.
Methods
In CASTING, patients with RRMS (Expanded Disability Status Scale [EDSS] score ≤4.0 at screening; disease duration ≤10 years) and a prior suboptimal response to ≥6 months of treatment with one or two disease-modifying therapies (DMTs; including orals and injectables) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. SymptoMScreen was performed at baseline, Week 48 (1-year interim data) and Week 96 (2-year final data).
Results
A total of 680 patients (female, 64%; mean [SD] baseline EDSS score, 2.1 [1.1]) who were previously treated with one (n=414 [60.4%]) or two (n=269 [39.6%]) DMTs were enrolled (most frequently for MRI with relapse activity [40.4%]) and evaluated in the intent-to-treat population; 644 patients completed treatment. Total SymptoMScreen mean (SD) score reflected mild symptom burden at baseline (15.19 [12.67]) and improved significantly through Year 2 (13.62 [12.51]; p<0.001 [p values were not adjusted for multiplicity]). Statistically significant improvements after 2 years were observed for sensory symptoms (Δ-0.28; p<0.001), fatigue (Δ-0.23; p<0.001), vision (Δ-0.21; p<0.001), depression (Δ-0.15; p<0.01) and dizziness (Δ-0.14; p<0.01) domains. Non-significant improvements in symptom burden after 2 years (p>0.05) were observed in walking (Δ-0.1), cognition (Δ-0.10), anxiety (Δ-0.07), bodily pain (Δ-0.05), hand function (Δ-0.03) and bladder control (Δ-0.01), while a non-significant worsening was observed in the spasticity domain (Δ+0.04). The proportion of patients with at least one symptom causing at least moderate limitation (domain score ≥4) decreased from 31.6% at baseline to 26.3% at Year 2.
Conclusions
Patients with RRMS and a suboptimal response to therapy who switched to ocrelizumab experienced an improvement in symptom burden in the majority of SymptoMScreen domains after 2 years, which was most pronounced in sensory, fatigue and vision.