University of California

Author Of 1 Presentation

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

PS15.03 - Optical coherence tomography in aquaporin-4-IgG positive neuromyelitis optica spectrum disorders: a collaborative multi-center study

Abstract

Background

Optic neuritis (ON) is a frequent manifestation in aquaporin-4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (NMOSD). Due to limited samples, existing optical coherence tomography (OCT) studies are inconsistent regarding retinal changes in eyes with a history of ON (NMO-ON) and without a history of ON (NMO-NON), and their functional relevance.

Objectives

The CROCTINO (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica) project aims to reveal correlates of retinal pathology and to generate hypotheses for prospective OCT studies in NMOSD. The objective of this study was to analyze retinal changes of AQP4-IgG seropositive NMO-ON and NMO-NON eyes in an international cross-sectional OCT dataset.

Methods

Of 656 subjects, we enrolled 283 AQP4-IgG seropositive NMOSD patients and 72 healthy controls (HC) from 22 international expert centers. OCT data was acquired with Spectralis SD-OCT, Cirrus HD-OCT and Topcon 3D OCT-1. Mean thickness for the combined ganglion cell and inner plexiform layer (GCIP) and inner nuclear layer (INL) were calculated from macular volume scans. Clinical, functional and laboratory testing were performed at discretion of each center.

Results

We compared NMO-ON eyes (N = 260), NMO-NON eyes (N = 241) and HC eyes (N = 136). GCIP was reduced in NMO-ON (57.4 ± 12.2 µm) compared with NMO-NON (75.9 ± 7.7 µm; p < 0.001) and HC (81.4 ± 5.7 µm; p < 0.001). NMO-NON had thinner GCIP (p < 0.001) compared with HC. INL was thicker in NMO-ON (40.3 ± 3.9 µm) compared with NMO-NON (38.6 ± 3.9µm; p < 0.001), but not HC (39.4 ± 2.6 µm). Microcystic macular edema were visible in 6.6 % of NMOSD eyes.

Conclusions

AQP4-IgG seropositive NMOSD is characterized by a functionally relevant loss of retinal neuroaxonal content and a - probably inflammatory - increase of INL after ON. Our study further supports the existence of attack-independent damage in the visual system of patients with AQP4-IgG seropositive NMOSD.

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Author Of 6 Presentations

Imaging Late Breaking Abstracts

LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)

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.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0689 - Autoimmune comorbidity increases healthcare cost burden in patients with NMOSD in the United States: a retrospective commercial claims analysis   (ID 1053)

Speakers
Presentation Number
P0689
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that may be associated with specific comorbidities, including autoimmune disease (AID) or nonautoimmune conditions. This study assessed real-world healthcare utilization and cost of illness in patients with NMOSD and overlapping AID.

Objectives

To evaluate the cost of illness in patients with NMOSD with overlapping AID compared with controls without NMOSD (non-NMOSD) and NMOSD without comorbid AID in US commercial claims databases.

Methods

Methods

Claims data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases were analyzed between 2014 and 2018. Patients were identified as having NMOSD if they had ≥1 inpatient or ≥2 outpatient claims for NMOSD diagnosis ≥60 days apart or ≥2 claims for transverse myelitis diagnosis in combination with ≥1 claim for optic neuritis ≥6 months apart. Continuous enrollment ≥6 months before and ≥1 year after the first claim (index date) was required. Non-NMOSD controls were matched 5:1 to patients with NMOSD. Total costs stratified by AID in consumer price index–adjusted 2019 US dollars within 12 months post–index date were calculated for each patient.

Results

In the NMOSD group, 31/162 patients (19.1%) had AID compared with 40/810 matched non-NMOSD controls (4.9%), with 8/162 (4.9%) in the NMSOD group having multiple AIDs vs 5/810 (0.6%) in matched non-NMOSD controls. These included systemic lupus erythematous (SLE; 5.6% vs 0.4%; p<0.001), rheumatoid arthritis (RA; 4.3% vs 0.9%; p=0.004), Sjögren syndrome (SS; 3.1% vs 0.1%; p<0.001), and autoimmune encephalitis (AE; 2.5% vs 0%; p<0.001). Total median [IQR] costs per patient during the post-index follow-up period were significantly higher for patients with NMOSD and AID ($68,386 [$23,374–$160,863]) than both matched non-NMOSD controls with AID ($17,215 [$6,715–$31,442]; p<0.001) and NMOSD without AID ($23,905 [$8,633–$67,252]; p=0.022). This trend held across all settings, including inpatient care, outpatient care, outpatient emergency room services and pharmacy expenses.

Conclusions

Patients with NMOSD and comorbid AID incurred significantly higher costs associated with healthcare resource utilization compared with matched non-NMOSD controls and patients with NMOSD who did not have AID. These results demonstrate a higher cost burden associated with overlapping AID (primarily SLE, RA, SS and AE) in patients with NMOSD and a need to identify more cost-efficient, integrated therapeutic approaches to address the overlap of NMOSD and other serious, debilitating AID.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0694 - Burden of autoimmune comorbidity in patients with NMOSD in the United States revealed by retrospective commercial claims analysis (ID 1051)

Speakers
Presentation Number
P0694
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition of the central nervous system that may be associated with concomitant autoimmune disease (CAID), such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), as well as nonautoimmune conditions (CnAID).

Objectives

To evaluate the burden of CAID in patients with NMOSD compared with controls without NMOSD (non-NMOSD) in US commercial claims databases.

Methods

Claims data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases were analyzed between 2014 and 2018. Patients were identified as having NMOSD if they had ≥1 inpatient or ≥2 outpatient claims for NMOSD diagnosis ≥60 days apart or ≥2 claims for transverse myelitis diagnosis in combination with ≥1 claim for optic neuritis ≥6 months apart. Continuous enrollment ≥6 months before and ≥1 year after the first claim (index date) was required. Non-NMOSD controls were matched 5:1 to patients with NMOSD. The Charlson Comorbidity Index (CCI) was assessed during a 6-month baseline period prior to NMOSD diagnosis and at 12 months post-index. Comorbidities during the 12-month follow-up period were evaluated.

Results

A total of 162 patients with NMOSD (mean [SD] age, 43.3 [18] years) and 810 non-NMOSD controls (mean [SD] age, 43.3 [18] years) were evaluated. Mean (SD) 6-month baseline and 12-month follow-up CCI scores were 0.96 (1.77) and 1.62 (2.53) for patients with NMOSD vs 0.34 (0.91) and 0.52 (1.31) for non-NMOSD controls, respectively (p<0.001). CAID occurred in 19.1% vs 4.9% (p<0.001) of NMOSD patients vs non-NMOSD controls. SLE (5.6% vs 0.4%; p<0.001), RA (4.3% vs 0.9%; p=0.004), Sjögren syndrome (3.1% vs 0.1%; p<0.001) and autoimmune encephalitis (2.5% vs 0%; p<0.001) occurred at significantly higher prevalence in patients with NMOSD. Reports of type 1 diabetes (1.9% vs 1.4%) and myasthenia gravis (1.2% vs 0.1%) were not significantly different between the NMOSD and non-NMOSD groups in this study cohort.

Conclusions

Patients with NMOSD had significantly higher CCI scores and CAID prevalence compared with controls. Consistent with previous studies, these results highlight the significant CAID burden in NMOSD. Moreover, these data suggest immune dysfunction common to multiple autoimmune diseases and underscore the need to identify efficacious therapies with distinct mechanisms of action to address the concomitant burden of NMOSD and other debilitating CAIDs.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0695 - Burden of disease in patients with neuromyelitis optica spectrum disorder: insights from the CIRCLES study cohort (ID 802)

Speakers
Presentation Number
P0695
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

In patients with neuromyelitis optica spectrum disorder (NMOSD), relapses may result in cumulative neurological damage and disability. Disease burden may include pain, sensory, cognitive and visual impairment, bowel/bladder dysfunction, weakness or paralysis, and necessitate caregiver support. Prior to 2019, no therapies had received regulatory approval for NMOSD. Thus, off-label immunosuppressive therapies (IST) were commonly used for maintenance therapy. CIRCLES is a prospective, longitudinal, cross-sectional study of disease epidemiology and treatment in North American patients with NMOSD.

Objectives

This study analyzed real-world disease burden in North American patients with NMOSD enrolled in the CIRCLES study from 2013 to 2019.

Methods

Of 629 CIRCLES participants, 523 (83.1%) with anti-aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) NMOSD were assessed for disease burden, including vision loss, paralysis, annual relapse rate (ARR) relative to mobility level, and steroid side effects.

Results

Baseline assessment of disability indicated at least partial (136/523, 26.0%) or complete (55/523, 10.5%) dependence on caregiver support. Among patients on off-label maintenance IST and having ≥60 days of on-study follow-up (n = 469), 136 (29.0%) experienced a total of 209 on-study relapses. The unadjusted ARR (95% confidence interval [CI]) by mobility level was 0.17 (0.14–0.20), 0.21 (0.16–0.27), and 0.24 (0.16–0.34) for independent, partially dependent, and completely dependent patients, respectively. Side effects from steroids were assessed in 429 respondents, of whom, 35 (8.2%) had gastroesophageal reflux disease, 30 (6.9%) had depression/anxiety, and 28 (6.5%) had osteoporosis. Of 77 patients with on-study relapses and vision assessment, 24 (31.2%) had vision loss (unadjusted ARR, 0.18 [CI, 0.13–0.24]; P > 0.05 vs. no relapses). Furthermore, of 129 patients with on-study relapses and paralysis assessment, 68 (52.7%) had partial or complete paralysis (unadjusted ARR, 0.23 [CI, 0.19–0.27]; P = 0.03 vs. no relapses).

Conclusions

NMOSD imposes significant disease burden, including vision loss and paralysis resulting in dependence on caregiver support in over one-third of patients. Despite the use of off-label maintenance ISTs, a substantial proportion of patients with NMOSD continue to experience relapses, disability, and neurological damage. These findings underscore the need for safe, effective, and well-tolerated treatments for preventing relapses.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0705 - Cost of illness for patients with NMOSD and nonautoimmune disease estimated from claims databases in the United States   (ID 1054)

Speakers
Presentation Number
P0705
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that often results in substantial neurological deficits and disability. NMOSD has been associated with various comorbidities, including autoimmune conditions, cardiovascular disease (CD) and type II diabetes (DMII). In this analysis, real-world healthcare utilization and cost of illness were analyzed in patients with NMOSD and concomitant nonautoimmune morbidities (CnAIDs).

Objectives

To evaluate the cost of illness in patients with NMOSD and CnAID compared with controls without NMOSD (non-NMOSD) or NMOSD without CnAID in US commercial claims databases.

Methods

This study used claims from the Truven Health MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018. Patients were identified as having NMOSD if they had ≥1 inpatient or ≥2 outpatient claims for NMOSD diagnosis ≥60 days apart or ≥2 claims for transverse myelitis diagnosis in combination with ≥1 claim for optic neuritis ≥6 months apart. Continuous enrollment ≥6 months before and ≥1 year after the first claim (index date) was required. Non-NMOSD controls were matched 5:1 to patients with NMOSD. Total costs stratified by CnAID in consumer price index–adjusted 2019 US dollars within 12 months post–index date were calculated for each patient.

Results

In the NMOSD group, 100/162 patients (61.7%) had ≥1 CnAIDs vs 328/810 (40.5%) matched non-NMOSD controls, with 60/162 (37.0%) in the NMOSD group having multiple CnAIDs vs 177/810 (21.9%) in matched non-NMOSD controls. These included CD (27.2% vs 10.1%; p<0.001), DMII (15.4% vs 8.6%; p=0.013), hyperglycemia (HG; 7.4% vs 3.2%; p=0.023) or liver disease (LD, excludes infection; 6.8% vs 2.4%; p=0.009). Total median [IQR] healthcare costs per patient during the postindex follow-up period were significantly higher for patients with NMOSD and CnAID ($36,618 [$13,503–$116,645]) vs matched non-NMOSD controls with CnAID ($4,960 [$1,709–$13,654]; p<0.001) or NMOSD without CnAID ($21,644 [$6,339–$55,061]; p=0.041).

Conclusions

Patients with NMOSD and CnAID incurred significantly higher costs associated with healthcare resource utilization compared with non-NMOSD matched controls or patients with NMOSD but without CnAID. These results demonstrate the higher CnAID prevalence and subsequent cost burden associated with CnAID (primarily CD, DMII, HG and LD) in patients with NMOSD and therefore the need to identify more cost-efficient, integrated therapeutic approaches to address the overlap of NMOSD and comorbidities.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0712 - Estimating the cost of illness for patients with neuromyelitis optica spectrum disorder from US commercial claims (ID 984)

Speakers
Presentation Number
P0712
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that often leads to accumulation of severe disability. Patients with highly active NMOSD have a roughly 10-times higher hospital inpatient admission rate compared with patients without NMOSD. Limited data have been published on the cost of illness for patients with NMOSD, including treatment with rescue therapies (RTs) and use of health services in the emergency room (ER) and inpatient hospital settings.

Objectives

To evaluate the cost of illness related to ER visits, hospitalizations and RTs in patients with NMOSD compared with controls without NMOSD (non-NMOSD) in US commercial claims databases.

Methods

This study used claims from the Truven Health MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018. Patients were identified as having NMOSD if they had ≥1 inpatient or ≥2 outpatient claims for NMO diagnosis ≥60 days apart or ≥2 claims for transverse myelitis diagnosis in combination with ≥1 claim for optic neuritis ≥6 months apart. Continuous enrollment ≥6 months before and ≥1 year after the first claim (index date) was required. Non-NMOSD controls were matched 5:1 to patients with NMOSD. Total costs of ER visits and hospitalizations in consumer price index–adjusted 2019 US dollars within 12 months post–index date were calculated for each patient.

Results

A total of 162 patients with NMOSD (mean [SD] age, 43.3 [18] years) and 810 non-NMOSD controls (mean [SD] age, 43.3 [18] years) were evaluated. ER visits and hospitalizations for NMOSD vs non-NMOSD groups occurred in 35.8% vs 16.9% and 41.4% vs 5.1% of patients (p<0.001 for both), and mean (SD) time in hospital was 21.2 (32.7) vs 5.24 (6.46; p<0.001) days, respectively. Nearly 12% of patients with NMOSD were treated with RTs (intravenous immunoglobulin [IVIG] or plasma exchange [PLEX]) vs none for non-NMOSD controls. Mean (SD) costs per patient were $2,400 ($7,771) vs $408 ($2,579) for ER visits, $29,054 ($144,872) vs $1,521 ($10,759) for hospitalizations and $912.73 ($5,032.75) vs $0 for IVIG/PLEX for the NMOSD vs non-NMOSD groups (p<0.001 for all).

Conclusions

Compared with controls, patients with NMOSD had significantly longer hospital stays and higher costs associated with ER visits, hospitalizations and RTs. These results highlight the severity of NMOSD, the economic burden of illness, and the unmet need for more safe and effective treatments.

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