Original article
Asian and African/Caribbean AQP4-NMOSD patient outcomes according to self-identified race and place of residence

https://doi.org/10.1016/j.msard.2021.103080Get rights and content

Highlights

  • •

    Place of residence may be a driver of disability among African/Caribbean NMO patients.

  • •

    Place of residence may not be a significant driver of NMOSD disability among Asian patients.

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    African/Caribbean NMO patients had higher first attack visual disability.

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence.

Methods

This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three.

Results

Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups.

Conclusion

This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors.

Introduction

Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune astrocytopathy, with secondary demyelination, characterized by antibodies against aquaporin-4. The optic nerve and spinal cord are usually involved, with less frequent involvement of brain sites (area postrema, brainstem, diencephalon) (Wingerchuk et al., 2015).

Onset age, genetic factors such as race, environmental exposures and immunosuppression are reported to influence NMOSD prognosis (Eskandarieh et al., 2018; Kim et al., 2018; Mealy et al., 2014; Palace et al., 2019; Tackley et al., 2016). Several large studies have examined the impact of race on NMOSD risk and outcomes (Kim et al., 2018; Tackley et al., 2016). The condition appears to be more prevalent in patients of Asian and African descent (Flanagan et al., 2016). Some studies suggest Japanese patients have milder outcomes (Kitley et al., 2012) and patients of African descent appear to have younger onset age, worse visual prognosis, higher relapse rate and higher frequency of brain attacks when compared with white (Cabrera-Gomez et al., 2009; Kim et al., 2018; Mealy et al., 2018; Palace et al., 2019; Tackley et al., 2016). Distinguishing the relative contribution of environmental factors and/or treatment management from genetics and race is challenging, especially since race is considerably homogeneous within a center.

A conceivable approach to tackle this issue would be to compare the outcomes of each racial group in their native country with those who are not autochthonous. Therefore, our current work aims to compare the outcomes of NMOSD patients, according to their race and residence, by merging data from multiple international NMOSD centers.

Section snippets

Study design

In this retrospective descriptive cohort study, we included 839 non-white patients with aquaporin-4 antibody positive (AQP4-Ab) and MOG antibody negative NMOSD between March 2017-January 2019 from patient databases pertaining to 15 centers: University of Southern Denmark (Vejle)(n = 1), Strasbourg University Hospital (France)(n = 3), Charité - Universitätsmedizin (Berlin, Germany)(n = 2), University of Oxford (UK)(n = 88), the Walton Center (Liverpool, UK)(n = 20), Johns Hopkins University

Baseline characteristics

Table 1 shows the clinical and demographic characteristics of the 821 AQP4-Ab positive patients. There was no AQP4/MOG double positivity. There were 206 African/Caribbean, 65 South Asian and 550 East Asian patients. We further excluded one South Asian patient living in East Asia. Median follow-up time was 7.4 (IQR 3.7–12.5; range 0.02–47.9) years. The female:male ratio was 9:1 and median age of onset was 37 years (IQR 28–49, range 2–84). Median AAR was 0.54 (IQR 0.33–0.88, range 0.04–6)

Discussion

This is the first study reporting the effects of place of residence on the outcomes in different self-identified racial groups with AQP4-Ab positive NMOSD. No significant differences between natives from Asian countries and those living outside Asia was seen, although there appeared to be a difference in outcome between the Asian sites. African/Caribbean natives displayed a higher prevalence of visual disability from initial attack and significantly higher hazard of progression to higher

Funding

No funding sources directly financed this study.

CRediT authorship contribution statement

Ricardo Soares-dos-Reis: Formal analysis, Investigation, Data curtion, Project administration, Writing – original draft, Writing – review & editing, Visualization. Jessica Li Tsz-Ching: Methodology, Investigation, Project administration, Resources, Data curtion, Writing – review & editing. Su-Hyun Kim: Resources, Investigation, Data curtion, Writing – review & editing. Anu Jacob: Resources, Investigation, Data curtion, Writing – review & editing. Daniel Whittam: Resources, Investigation, Data

Declaration of Competing Interest

Dr. Kim reports grants from National Research Foundation of Korea, personal fees from Alexion Pharmaceuticals, Aprilbio, Celltrion, Eisai, HanAll BioPharma, MDimume, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and Viela Bio, other from Viela Bio (formerly MedImmune), other from Multiple Sclerosis Journal, other from Journal of Clinical Neurology, outside the submitted work.

Dr. Palace reports grants, personal fees and other from Alexion Pharmaceuticals Inc, during the conduct of the

Acknowledgments

Dr. Pittock was supported by the Mayo Clinic Center for MS and Autoimmune Neurology. Dr. Yang received grants from the National Nature Science Foundation of China (Grant number: 81771363, 81471221). Dr. Yeo is supported by the Ministry of Health, Singapore through the National Medical Research Council Research Training Fellowship (NMRC/Fellowship/0038/2016).

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