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The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>CIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with\u2009\u2265\u200960\u00a0days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of 542 patients included, 171 (31.5%) experienced\u2009\u2265\u20091 relapse on the study and 133 patients (24.5%) had\u2009\u2265\u20091 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR]\u2009=\u20092.91; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), relapse phenotypes (HR range\u2009=\u20092.15\u20135.49; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and pre-study ARR\u2009&gt;\u20090.75 (HR 2.28; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; <jats:italic>p<\/jats:italic>\u2009=\u20090.008), disease duration\u2009&lt;\u20091 vs\u2009&gt;\u20095\u00a0years (HR 1.66; <jats:italic>p<\/jats:italic>\u2009=\u20090.028), or autoimmune comorbidity (HR 1.55; <jats:italic>p<\/jats:italic>\u2009=\u20090.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-022-11529-6","type":"journal-article","created":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T12:02:36Z","timestamp":1671883356000},"page":"2048-2058","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort"],"prefix":"10.1007","volume":"270","author":[{"given":"Shervin","family":"Gholizadeh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Exuzides","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelyn 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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. KE Lewis, C Palmer, M Waltz, and AM Jolley declare that they have nothing to disclose. JW Rose has received research support from the National Multiple Sclerosis Society, Guthy-Jackson Charitable Foundation, National Institutes of Health (NIH), Friends of MS\u00a0and Biogen. He has received intellectual property interests from a discovery or technology relating to health care. JM Behne has received personal compensation as Executive Director of the Guthy-Jackson Charitable Foundation. MK Behne has received personal compensation for serving as an independent contractor with the Guthy-Jackson Charitable Foundation. TF 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. TJ Smith has received personal compensation as an advisor to the Guthy-Jackson Charitable Foundation. He 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 discoveries and technologies relating to health care. J Sinnott has received research support from the Guthy-Jackson Charitable Foundation and the NIH. LJ Cook has received research support from the Centers for Disease Control and Prevention, Guthy-Jackson Charitable Foundation, Utah Highway Safety Office and NIH. MR Yeaman has received personal compensation as an advisor to the Guthy-Jackson Charitable Foundation. He has received personal compensation for serving on a scientific advisory board for Genentech. He has received honoraria from Roche, Horizon and Alexion for scientific presentations pertaining to NMOSD. He has received research support from the NIH (National Institute of Allergy and Infectious Disease) and the US Department of Defense. He holds numerous patents and has received intellectual property interests from discoveries and technologies relating to health care.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"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.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written and verbal consent or assent was obtained before beginning the study procedures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}