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However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13064-6","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T13:44:56Z","timestamp":1744638296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Progression independent of relapse activity and relapse-associated worsening in seronegative NMOSD: an international cohort study"],"prefix":"10.1007","volume":"272","author":[{"given":"Pakeeran","family":"Siriratnam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif","family":"Huda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Van der 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Siriratnam has received travel support from Novartis and Biogen; S. Huda is funded by an NIHR SCPRA grant; A.VD Walt has received travel support and served on advisory boards for Novartis, Biogen, Merck Serono, Roche, and Teva, and receives grant support from the National Health and Medical Research Council of Australia; P.G. Sanfilippo reports no relevant disclosures; S. Sharmin has received postdoctoral fellowship from the MSBase Foundation and MS Australia; Yi.C. Foong has received travel support from Roche and Biogen, and receives grant support from Australian National Health Medical Research Council, Australia and New Zealand Association of Neurologists, AVANT foundation, and MS Research Australia; W.Z. Yeh has received speaker honoraria from Merck and Novartis; C. Zhu receives fellowship from the Trish Multiple Sclerosis Research Foundation; S.J. Khoury received compensation for scientific advisory board activity from Merck and Roche, and received compensation for serving on the IDMC for Biogen; T. Csepany received speaker honoraria\/conference travel support from Biogen, Merck, Novartis, Roche, Sanofi-Aventis, and Teva; B. Willekens received honoraria for acting as a member of Scientific Advisory Boards\/Consultancy for Alexion, Almirall, Biogen, Celgene\/BMS, Merck, Janssen, Novartis, Roche, Sandoz, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Celgene\/BMS, Merck, Novartis, Roche, Sanofi-Genzyme, research and\/or patient support grants from Biogen, Janssen, Merck, Sanofi-Genzyme, Roche, paid honoraria and grants to UZA\/UZA Foundation, and received research funding from FWO-TBM, Belgian Charcot Foundation, Start2 Cure Foundation, Queen Elisabeth Medical Foundation for Neurosciences, and the National MS Society USA; M. Etemadifar reports no relevant disclosures; S. Ozakbas reports no relevant disclosures; P. Nytrova received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Roche, Jannsen, and Astra Zeneca and financial support for research activities from Roche and Merck, supported by Ministry of Health of the Czech Republic, grant nr. NU23 -\u200905\u201300462; A. Altintas received speaker honoraria from Novartis and Alexion; A. Al-Asmi received personal compensation for serving as a Scientific Advisory or speaker\/moderator for Novartis, Biogen, Roche, Sanofi-Genzyme, and Merck; C.M. Ramo-Tello has received consulting fees, speaker honoraria, support for attending meetings and\/or travel, participation on advisory board and research grants for her institution from Biogen, Novartis, Sanofi, Bristol, Roche, Almirall, Janssen, Sandoz, and Merck; G. Laureys received travel and\/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, and Biogen; F. Patti received personal compensation for serving on advisory board by Almirall, Alexion, Biogen, Bristol, Janssen, Merck, Novartis, and Roche, and received research grant from Alexion, Almirall, Biogen, Bristol, Merck, Novartis, and Roche and from FISM, Reload Association (Onlus), Italian Health Minister, and University of Catania; D. Horakova was supported by the Charles University: Cooperation Program in Neuroscience, by the project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22 NPO5107) \u2013 Funded by the European Union \u2013 Next Generation EU, and by General University Hospital in Prague project MH CZ-DRO-VFN64165, and received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi-Genzyme, Roche, and Teva, as well as support for research activities from Biogen Idec; M. Foschi received travel and meeting attendance support from Novartis, Biogen, Roche, Sanofi-Genzyme, and Merck; C. Boz received conference travel support from Biogen, Novartis, Bayer Schering, Merck, and Teva, and participated in clinical trials by Sanofi-Aventis, Roche, and Novartis; P. McCombe received honoraria and consulting fees from Novartis, Bayer Schering, and Sanofi and travel grants from Novartis, Biogen, and Bayer Schering; R. Turkoglu reports no relevant disclosures; J. Lechner-Scott received travel compensation from Novartis, Biogen, Roche, and Merck, and her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA, and Novartis; I. Roos has served on scientific advisory boards, received conference travel support and\/or speaker honoraria from Roche, Novartis, Merck, and Biogen, was supported by a MS Australia and the Trish Multiple Sclerosis Research Foundation; T. Kalincik served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi-Genzyme, Novartis, Merck, and Biogen, steering committee for Brain Atrophy Initiative by Sanofi-Genzyme, received conference travel support and\/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL, and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck; V. Jokubaitis receives fellowship and research support from the National Health and Medical Research Council of Australia and receives research grant support form F.Hoffmann La-Roche and the International Progressive MS Alliance; H. Butzkueven served on scientific advisory boards for Biogen, Novartis, and Sanofi-Aventis and received conference travel support from Novartis, Biogen, and Sanofi-Aventis, and serves on steering committees for trials conducted by Biogen and Novartis and received research support from Merck, Novartis, and Biogen, Medical Research Council, and MS Research Australia; M. Monif has served on advisory board for Merck and Novartis and has received speaker honoraria from Merck, Biogen, and Novartis, and her institution receives funding from Merck, Australian National Health.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"339"}}