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An overall cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009505) and a subset of these patients with an enriched dataset (<jats:italic>n<\/jats:italic>\u2009=\u2009198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG\u2013seropositive or \u2013seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61\u20135.90), vision (OR, 3.99; 95% CI: 2.03\u20137.86), self-care disability (OR, 1.90; 95% CI: 1.07\u20133.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71\u201310.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG\u2013seropositive status in patients\u2009\u2265\u200918 years (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Disease onset phenotype and sex correlated with pain interference (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.\u00a0<\/jats:p>","DOI":"10.1038\/s41598-024-75013-z","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T15:02:54Z","timestamp":1730300574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Assessment of disability and disease burden in neuromyelitis optica spectrum disorders in the CIRCLES Cohort"],"prefix":"10.1038","volume":"14","author":[{"given":"Shervin","family":"Gholizadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Exuzides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sinnott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chella","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Waltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Marie","family":"Jolley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinta M.","family":"Behne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan K.","family":"Behne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence F.","family":"Blaschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn E.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Yeaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of The Guthy-Jackson Charitable Foundation CIRCLES Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"75013_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1177\/1756285617709723","volume":"10","author":"SM Kim","year":"2017","unstructured":"Kim, S. 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Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75013-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75013-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75013-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T15:19:54Z","timestamp":1730301594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75013-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["75013"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-75013-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"assertion":[{"value":"1 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The CIRCLES study was sponsored by The Guthy-Jackson Charitable Foundation. The present study was funded by Genentech, Inc. S. Gholizadeh is an employee of Genentech, Inc., and shareholder of F. Hoffmann-La Roche Ltd. A. Exuzides was an employee of Genentech, Inc., at the time of this study and manuscript preparation and is a shareholder of F. Hoffmann-La Roche Ltd. J. Sinnott has received research support from the Guthy-Jackson Charitable Foundation and the National Institutes of Health (NIH). C. Palmer and M. Waltz declare they have nothing to disclose. J. Rose has received research support from the National Multiple Sclerosis Society, Guthy-Jackson Charitable Foundation, NIH, Friends of MS, Biogen, and the US Department of Veterans Affairs. He has received intellectual property interests from a discovery or technology relating to health care. A. Jolley and J.M. Behne declare they have nothing to disclose. M.K. Behne has received personal compensation for serving as an independent contractor with the Guthy-Jackson Charitable Foundation. T.F. Blaschke has received personal compensation for serving as a consultant for Merck, the Guthy-Jackson Charitable Foundation, and the Bill and Melinda Gates Foundation. He has received personal compensation for serving as an officer or member of the board of directors for Durect. He has received personal compensation for serving as an editor, associate editor, or editorial advisory board member for Annual Reviews. He has received stock or ownership interest from Durect. He has received research support from the Bill and Melinda Gates Foundation. T.J. Smith has received personal compensation for serving as a consultant for Horizon and Immunovant. He has received personal compensation for serving on a scientific advisory or data safety monitoring board for Horizon. He has received intellectual property interests from a discovery or technology relating to health care. He is an advisor to the Guthy-Jackson Charitable Foundation. M.R. Yeaman has received personal compensation for serving on a scientific advisory committee for Genentech, Alexion, and Horizon. He has received research support from the NIH and US Department of Defense. He has received intellectual property interests from a discovery or technology relating to health care. He is an advisor to the Guthy-Jackson Charitable Foundation. K. Lewis declares she has nothing to disclose. L. Cook has received research support from the Centers for Disease Control and Prevention, Guthy-Jackson Charitable Foundation, Utah Highway Safety Office, and NIH.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Enrollment was conducted in accordance with guidelines specified by the Office of Human Research Protections of the FDA. A standardized protocol, manual of operations, patient study file, and informed consent or assent documents were approved by institutional review boards or respective clinical study sites. All study protocols were approved by the University of Utah\/Data Coordinating Center Institutional Review Board, and\/or by respective CIRCLES study site Institutional Review Boards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Statement"}}],"article-number":"26150"}}