{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T18:17:38Z","timestamp":1773080258907,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To describe two cases of recurrent, delayed-onset severe neutropenia several months following ocrelizumab therapy in patients with relapsing\u2013remitting multiple sclerosis (RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A rare adverse effect of ocrelizumab is neutropenia, with late-onset neutropenia (LON) occurring more rarely. Literature guiding management of transient recurrent neutropenia in the setting of anti-CD20 therapy is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Case 1: 38-year-old female emergency physician with RRMS developed severe transient spontaneously resolving asymptomatic neutropenia 3\u202fmonths after ocrelizumab infusion. Two years later, she developed severe symptomatic LON and required antibiotics and granulocyte colony-stimulating factor (GCSF). Ocrelizumab was held, patient switched to ozanimod, but neutropenia recurred. Due to concerns of MS progression, ocrelizumab was restarted after the patient transitioned to a telehealth setting, with no recurrence of neutropenia at one-year follow-up. Case 2: 35-year-old male emergency physician with RRMS developed severe transient spontaneously resolving asymptomatic neutropenia 3\u202fmonths after ocrelizumab infusion. Ocrelizumab was resumed after absolute neutrophil count recovery. Two years later, he developed moderate symptomatic LON during a suspected viral illness. Ocrevus was discontinued at this point. A subsequent episode occurred 3\u202fmonths later during confirmed rhinovirus infection, again resolving promptly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These cases highlight the unpredictable nature of recurrent LON with ocrelizumab and suggest the possibility of immune-mediated marrow suppression, potentially unmasked or worsened by infections, rather than direct drug toxicity, highlighting the need for clearer management guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2025.1685209","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:22:15Z","timestamp":1763619735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Late-onset severe neutropenia in patients with relapsing remitting multiple sclerosis treated with ocrelizumab: case report and literature review"],"prefix":"10.3389","volume":"19","author":[{"given":"Catherine","family":"Tauro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeinab","family":"Awada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhika","family":"Malhotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asaff","family":"Harel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e51729","DOI":"10.7759\/cureus.51729","article-title":"A case of late-onset neutropenia in relapsing-remitting multiple sclerosis following Ocrelizumab therapy","volume":"16","author":"Alabdulqader","year":"2024","journal-title":"Cureus"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"102155","DOI":"10.1016\/j.msard.2020.102155","article-title":"Late-onset neutropenia in a multiple sclerosis patient after first-dose ocrelizumab switched from rituximab","volume":"45","author":"Auer","year":"2020","journal-title":"Mult. 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Sci."},{"key":"ref10","volume-title":"U.S. Food and Drug Administration","year":"2017"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1212\/WNL.54.11.2147","article-title":"Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor","volume":"54","author":"Openshaw","year":"2000","journal-title":"Neurology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e05299","DOI":"10.1002\/ccr3.5299","article-title":"Severe late-onset neutropenia induced by ocrelizumab in a multiple sclerosis patient: a case report","volume":"10","author":"Rauniyar","year":"2022","journal-title":"Clin. Case Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"102019","DOI":"10.1016\/j.msard.2020.102019","article-title":"Late-onset neutropenia after rituximab therapy for multiple sclerosis, neuromyelitis optica spectrum disorders, and MOG-antibodyassociated diseases","volume":"41","author":"Rigal","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"104090","DOI":"10.1016\/j.msard.2022.104090","article-title":"Neutropenia complicating anti-CD20 treatment in patients with multiple sclerosis: a retrospective case series and a systematic review of reported cases","volume":"68","author":"Rossi","year":"2022","journal-title":"Mult. Scler. Relat. 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Sci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/art.41504","article-title":"Incidence, clinical features, and outcomes of late-onset neutropenia from rituximab for autoimmune disease","volume":"73","author":"Zonozi","year":"2021","journal-title":"Arthritis Rheumatol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1685209\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:22:15Z","timestamp":1763619735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1685209\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":20,"alternative-id":["10.3389\/fnins.2025.1685209"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2025.1685209","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"article-number":"1685209"}}