Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune disease characterized by demyelination and axonal injury of the central nervous system. Serologic classification for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) can be useful and have been associated with diverse outcomes.

Objectives

To characterize NMOSD stratified by antibody serostatus (AQP4-IgG antibody positive, MOG-IgG antibody negative, and APQ4-IgG/MOG-IgG double negative) and evaluate predictors of disability outcomes.

Methods

This was a retrospective, single center study of 75 patients meeting NMOSD 2015 criteria who are seen and followed at a single center. AQP4-IgG and MOG-IgG antibodies were tested. The relationship between antibody status (AQP4-IgG+, MOG-IgG+) and double seronegative (DNeg) and DMT failure and Expanded Disability Status Scale (EDSS) was tested using multivariate linear regression (adjusted for age of onset, sex, race/ethnicity). DMT failure was defined as having to switch due to breakthrough disease on current DMT.

Results

Most were female (76.7%), Hispanic (62.7%), with a median age of onset of 39.0 (SD±13.9) and disease duration of 8.0 (SD±7.5). More than 2/3 (69%) were on rituximab. Presentation with optic neuritis or myelitis varied by seropositive types (P-value<0.05). APQ4-IgG+ presented more likely with optic neuritis (44.5%) while DNeg were more likely to present with myelitis (87%). Disability also differed significantly between the groups (p-value<0.05). About 40% of AQP4IgG+ and DNeg patients had EDSS>=4 while all MOG-IgG patients had EDSS<4. Greater odds of DMT failure was observed with being MOG-IgG+ (OR 2.9 95% CI 0.86-10.22) compared to AQP4-IgG+. After controlling for age, sex, age at onset and DMT failure, MOG-IgG+ patients had lower disability (mean EDSS:1.6, p-value<0.01) compared to AQP4-IgG+ and DNeg patients (mean EDSS:3.6).

Conclusions

In this predominant Hispanic sample of NMOSD, we confirm that MOG-IgG+ serostatus is an important biomarker of treatment failure. Treatment approaches specific to NMOSD MOG-IgG+ are warranted.

Background

Minority patients with multiple sclerosis (MS), including those of African ancestry (AA) and Hispanic and Latino ethnicity (HA), have greater disease severity and faster progression than Whites. Minorities are vastly underrepresented in clinical trials, owing to poor access and cultural, economic and other participation barriers. Ocrelizumab (OCR), an anti-CD20 therapy targeting B cells, reduced the rates of disease activity and progression in patients with relapsing MS (RMS) and primary progressive MS in pivotal studies; however, minority participation was <10%.

Objectives

To investigate the efficacy and safety of OCR in AA and HA patients with RMS (2017 McDonald criteria) who meet the US prescribing information criteria in a single-arm Phase IV clinical study designed exclusively to meet the needs of these specific demographic groups.

Methods

An industry-sponsored collaborative approach rooted in minority needs and known knowledge gaps was used.

Results

Key differences between CHIMES (NCT04377555) and other MS trials are as follows:

1. CHIMES was developed in collaboration with patients with MS, patient advocacy groups and investigators.

2. Inclusion criteria allow for ≈150–200 participants with specific, well-controlled, pre-existing comorbidities and baseline creatinine levels within race-specific limits; these factors may disproportionately limit minority patient qualification in other trials.

3. OCR was chosen because of the indications that AA patients with MS may have greater B-cell–mediated pathology, such as a higher CSF IgG index.

4. Written materials will be available in English and Spanish and will be reviewed by a minority patient panel to ensure that they are easy to understand.

5. To enable early results, the primary endpoint is disease activity, defined by the proportion of patients free of protocol-defined events (clinical relapses, CDP or MRI activity) at the end of year 1.

6. All patients may participate in the second-year extension to study disease progression and various biomarker endpoints.

7. One-third of patients will participate in a substudy to assess CSF-specific biomarkers at two time points.

Conclusions

Findings from CHIMES are expected to improve current understanding of MS disease biology, treatment response and clinical trial participation among AA and HA patients with MS, with the ultimate goals of increasing high-quality standard of care to traditionally underserved populations and enhancing equality through clinical research.

Background

Acculturation and socioeconomic (SES) factors are known to play a large role in racial and ethnic health disparities in the United States (US). Lower SES has been reported to increase the risk of disability progression in multiple sclerosis (MS) in whites. How these measures relate to early MS in vulnerable US populations is not known. This is being evaluated as part of GAHMS, a prospective longitudinal study of Genetic ancestry and Acculturation in Hispanic background with early MS.

Objectives

To examine the association of sociodemographic and acculturation measures in early MS disability in Hispanic/Latinx (Latinx).

Methods

Cross-sectional assessment of 219 self-identified US Latinx, including Puerto Rico. Early MS was defined as a diagnosis of <5 years. Sociodemographic status (SES) markers (education, household income, public assistance) and acculturation measures including language preference, place of birth, years in the US and Short Acculturation Scale for Hispanics (SASH; a composite measure of acculturation to US) were collected as part of the baseline examination. Bivariate correlations assessed SASH correlation with acculturation proxies. Unadjusted and adjusted multivariable logistic and linear regression were used to examine the relationship between ambulatory disability (using the Expanded Disability Status Scale; EDSS) and acculturation and SES.

Results

Most participants were female (75.8%), had a mean age of onset of 30.65 years (SD±13.93), had relapsing remitting MS (85.3%), and self-identified as Latinx with Caribbean (46.3%) or Mexican origin (37.8%). Most were overweight (BMI Mean: 28.9±8.04) and unemployment was reported by 35%. A strong correlation was seen between SASH and language preference (0.75, <0.0001) and place of birth (0.70, <0.0001). Increased odds of severe ambulatory disability was associated: with being male, longer disease duration, education of high school or less (3.90, 95%CI 0.33-45.65), household income <$60,000 (3.22, 95%CI 0.26-39.75), and acculturation to US culture (4.041, 95%CI 0.79-20.62) after adjustment. EDSS also increased with acculturation to US (Beta 0.53, p=0.05) and low income (Beta 0.80, p=0.02) using adjusted linear regression.

Conclusions

Our study reveals insights into early disability patterns among diverse Latinx heritage, in the context of SES and cultural integration differences defined by strong acculturation measures. Preservation of Latinx cultural heritage in the US could have the capacity to alter disease severity and be protective in Latinx with MS. Further sociocultural investigations are warranted.

Background

Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) share clinical presentations including brainstem syndromes. Internuclear ophthalmoplegia (INO) is characterized by paresis of ipsilateral eye adduction in horizontal gaze. It usually corresponds to a lesion in the medial longitudinal fasciculus (MLF) and is commonly seen in MS. However, it is unclear if INO is as common in NMOSD.

Objectives

To determine the comparative prevalence of INO in patients with NMOSD and MS and compare clinical features of both disease processes.

Methods

This was a retrospective study of patients who have an established diagnosis of NMOSD and MS and visited both neuro-ophthalmology and MS clinics between 2015 and 2020. We used ICD10 billing codes for MS (G35) and NMOSD (G36) and patients were identified as having an INO if documented at any time during follow up. Logistic regression was used to evaluate the likelihood of developing an INO for NMO vs. MS patients. Multivariable analysis was adjusted for age, race, gender, and length of follow up.

Results

259 patients (70 NMOSD, 180 MS) were analyzed. Age range was 21 to 79 years with a mean age of 36.2 (SD+ 13.6 years) and mean disease duration of 1.8 years (SD + 4.6 years). Mean follow-up was 9.69 + 8.3 years. Most of the NMOSD patients were seropositive for AQP4 antibody (67.1%, n=47) followed by MOG antibody (17.1%, n=12). The overall frequency of INO in NMOSD was 1.4% (n=1) compared to 16% (n=30) in MS. Adjusted analysis showed that NMOSD patients were 9 times (OR: 0.112, 95% CI: 0.014-0.902, p=0.04) less likely to develop an INO compared to those with MS.

Conclusions

Our results show that NMOSD patients are less likely to develop an INO than MS patients at any point during their disease course. This suggests that INO and consequently MLF lesions are less common in NMOSD. Clinical implications lie in differentiation of NMOSD from MS and earlier pursuit of appropriate therapy.