{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:08:17Z","timestamp":1783062497603,"version":"3.54.6"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Aquaporin\u20104\u2010IgG\u2010positive neuromyelitis optica spectrum disorder (AQP4\u2010IgG+ NMOSD) can cause significant disability after a single attack. Long\u2010term immunotherapy reduces disability accumulation, but the choice of first\u2010line therapy varies. In the United Kingdom, rituximab is typically used as escalation therapy after conventional immunosuppressants fail, while in Germany, it is widely used as first\u2010line treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared attack risk and disability outcomes based on the Expanded Disability Status Scale (EDSS) in AQP4\u2010IgG+ NMOSD patients treated with rituximab as first\u2010line versus escalation therapy. Furthermore, attack suppression and risk factors for attacks in individuals who received treatment with azathioprine and mycophenolate mofetil (with\/without escalating to rituximab) were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The risk of attack was lower in individuals who received rituximab as first\u2010line therapy (<jats:italic>n<\/jats:italic>\u2009=\u200952) compared to escalation therapy (<jats:italic>n<\/jats:italic>\u2009=\u200981, HR\u2009=\u20090.45, 95% CI\u2009=\u20090.30\u20130.67). Once escalated to rituximab, there was no altered risk of attack between first\u2010line rituximab and escalation therapy (HR\u2009=\u20091.15, 95% CI\u2009=\u20090.64\u20132.08). Rituximab as first\u2010line compared to escalation therapy was associated with lower EDSS scores at therapy start (3.0 vs. 6.0, <jats:italic>p<\/jats:italic>\u2009=\u20091.10 \u00d7\u200910<jats:sup>\u22123<\/jats:sup>). In patients who remained on azathioprine or mycophenolate mofetil (<jats:italic>n<\/jats:italic>\u2009=\u200945), age\u2009&lt;\u200950\u2009years and treatment with azathioprine were identified as risk factors for attacks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rituximab as a first\u2010line therapy shows significant reduction in disability accumulation compared to escalation treatments. However, a subgroup of patients with AQP4\u2010IgG+ NMOSD may still respond well to conventional immunosuppression\u2014specifically older patients treated with mycophenolate mofetil.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70243","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T10:34:58Z","timestamp":1749551698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rituximab as First\u2010Line Compared to Escalation Immunotherapy Is Associated With Lower Disability Accumulation in Aquaporin\u20104\u2010<scp>IgG<\/scp>\u2010Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter Cohort Study From Germany and the United Kingdom"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9877-6987","authenticated-orcid":false,"given":"Daniel","family":"Engels","sequence":"first","affiliation":[{"name":"Institute of Clinical Neuroimmunology and Biomedical Center (BMC), LMU University Hospital, Faculty of Medicine Ludwig\u2010Maximilians\u2010University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rocchi","sequence":"additional","affiliation":[{"name":"Department of Neurology Walton Centre NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirasol","family":"Forcadela","sequence":"additional","affiliation":[{"name":"Department of Neurology Walton Centre NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pakeeran","family":"Siriratnam","sequence":"additional","affiliation":[{"name":"Department of Neurology Walton Centre NHS Foundation Trust  Liverpool UK"},{"name":"School of Translational Medicine Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Ringelstein","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf  Duesseldorf Germany"},{"name":"Department of Neurology, Center for Neurology and Neuropsychiatry LVR\u2010Klinikum, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-2343","authenticated-orcid":false,"given":"Martin W.","family":"H\u00fcmmert","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-2334","authenticated-orcid":false,"given":"Katrin","family":"Giglhuber","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine and Health Technical University Munich, Klinikum Rechts der Isar  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9650-6222","authenticated-orcid":false,"given":"Achim","family":"Berthele","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine and Health Technical University Munich, Klinikum Rechts der Isar  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Trebst","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan","family":"Aktas","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf  Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-1340","authenticated-orcid":false,"given":"Joachim","family":"Havla","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology and Biomedical Center (BMC), LMU University Hospital, Faculty of Medicine Ludwig\u2010Maximilians\u2010University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-3750","authenticated-orcid":false,"given":"Saif","family":"Huda","sequence":"additional","affiliation":[{"name":"University of Liverpool  Liverpool UK"},{"name":"Walton Centre NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-5268","authenticated-orcid":false,"given":"Tania","family":"K\u00fcmpfel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology and Biomedical Center (BMC), LMU University Hospital, Faculty of Medicine Ludwig\u2010Maximilians\u2010University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1099376"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.05.011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103882"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102377\u201014\u201051"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30066\u20101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30070\u20103"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)31817\u20103"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26626"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900866"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30078\u20108"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010023\u201011910\u2010z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200124"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010017\u20108590\u20100"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102022\u2010330714"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20101331.2010.03066.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010013\u20107169\u20107"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15406"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010021\u201002249\u20101"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102024\u2010334764"},{"issue":"4","key":"e_1_2_10_23_1","first-page":"51","article-title":"Comparative Analysis of Treatment Outcomes in Patients With Neuromyelitis Optica Spectrum Disorder Treated With Rituximab, Azathioprine, and Mycophenolate Mofetil: A Systematic Review and Meta\u2010Analysis","volume":"19","author":"Magdalena C.","year":"2022","journal-title":"Innovations in Clinical Neuroscience"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009245"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010021\u201000298\u20105"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.19\u20102\u2010169"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.106160"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105452"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5699"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.08.009"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201073882\u20108"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104730"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T13:48:44Z","timestamp":1750945724000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.70243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/ene.70243"],"URL":"https:\/\/doi.org\/10.1111\/ene.70243","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70243"}}