{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:14:38Z","timestamp":1789496078122,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Extended interval dosing protocols of B\u2010cell\u2010depleting therapies in multiple sclerosis (MS) are being developed, but intervals between infusions are often arbitrary. We describe total and memory B\u2010cell repopulation dynamics in MS patients on a memory B\u2010cell\u2010guided extended interval dosing ocrelizumab (OCR) protocol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>OCR was administered on peripheral CD19+ CD27+ memory B\u2010cell repopulation (\u22651\u2009cell\/\u03bcL), monitored using fluorescence\u2010activated cell sorting. Associations with CD19+ B\u2009cells and CD19+ CD27+ memory B\u2009cells were tested using mixed\u2010effect hurdle models, with rate ratios (RR) predicting cell counts and odds ratios (OR) predicting cell depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We collected 1,369 samples from 101 patients, 61.4% women, aged 42.2\u2009years (IQR 32.3\u201351.1\u2009years) and follow up 4.1\u2009years (IQR 2.9\u20135.2\u2009years). The median time between samples and previous OCR infusion was 6.6\u2009months (IQR 4.7\u20138.8\u2009months). Time since previous OCR infusion was positively associated with CD19+ B\u2009cells (RR\u2009=\u20091.11, 95% CI 1.10\u20131.11,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and CD19+ CD27+ memory B\u2010cell counts (RR\u2009=\u20091.11, 95% CI 1.09\u20131.13,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). A greater cumulative OCR dose was associated with persistent CD19+ CD27+ memory B\u2010cell depletion (OR 1.90, 1.57\u20132.31,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). CD19+ B\u2010cell repopulation was inversely associated with age (RR\u2009=\u20090.82, 95% CI 0.71\u20130.95,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010). Female patients showed a lower ratio of CD19+ CD27+ memory B\u2009cells\/total CD19+ B\u2009cells (RR\u2009=\u20090.42, 95% CI 0.26\u20130.69,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Disease activity was low, with most radiological activity observed within the first year of OCR treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Memory B\u2010cell repopulation becomes slower with increasing cumulative OCR dose. Age\u2010 and sex\u2010related mechanisms probably influence repopulation dynamics. Given the evidence for a pathogenic role of memory B\u2009cells, these observations could be considered when planning extended interval dosing strategies of OCR treatment. ANN NEUROL 2025;98:603\u2013615<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27281","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T07:13:23Z","timestamp":1749626003000},"page":"603-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of Cumulative Exposure to Ocrelizumab on Memory B\u2010Cell Repopulation Dynamics in Multiple Sclerosis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8512-6096","authenticated-orcid":false,"given":"Giulio","family":"Disanto","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Center, Department of Neurology, Neurocenter of Southern Switzerland (NSI), Regional Hospital of Lugano Ente Ospedaliero Cantonale  Lugano Switzerland"},{"name":"Faculty of Biomedical Sciences University of Italian Switzerland (USI)  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Sacco","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Department of Neurology, Neurocenter of Southern Switzerland (NSI), Regional Hospital of Lugano Ente Ospedaliero Cantonale  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Mallucci","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Department of Neurology, Neurocenter of Southern Switzerland (NSI), Regional Hospital of Lugano Ente Ospedaliero Cantonale  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zecca","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Department of Neurology, Neurocenter of Southern Switzerland (NSI), Regional Hospital of Lugano Ente Ospedaliero Cantonale  Lugano Switzerland"},{"name":"Faculty of Biomedical Sciences University of Italian Switzerland (USI)  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Department of Neurology, Neurocenter of Southern Switzerland (NSI), Regional Hospital of Lugano Ente Ospedaliero Cantonale  Lugano Switzerland"},{"name":"Faculty of Biomedical Sciences University of Italian Switzerland (USI)  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601277"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606468"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.3365"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001035"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01289-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15891"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2023.05.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211028833"},{"key":"e_1_2_9_11_1","volume-title":"ECTRIMS Copenaghen","author":"Hogenboom L","year":"2024"},{"key":"e_1_2_9_12_1","unstructured":"Kotulska\u2010JozwiakK ValerianiM MarS et al.Ocrelizumab dose selection for treatment of paediatric relapsing\u2010remitting multiple sclerosis: Pharmacokinetic safety and efficacy results from OPERETTA 1 (NCT04075266). 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