{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:06:14Z","timestamp":1784696774758,"version":"3.55.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Natalizumab (NTZ) is a high-efficacy therapy for relapsing-remitting multiple sclerosis (RRMS) that can be administered intravenously (IV) or subcutaneously (SC). While switching from IV to SC NTZ is increasingly common in clinical practice, evidence on pharmacodynamic stability, particularly under extended interval dosing (6 weeks), remains limited. This study aimed to evaluate CD49d receptor occupancy (RO), serum neurofilament light chain (sNfL) levels, and clinical outcomes in RRMS patients switching from IV to SC NTZ while maintaining either 4- or 6-week dosing intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter, ambispective, observational study including RRMS patients who had received IV NTZ for at least 6 months on a 4w or 6w schedule and subsequently switched to SC NTZ while maintaining the same dosing interval. CD49d RO was assessed in CD4+, CD8+, and CD19+ lymphocyte subsets before the first, third, and seventh SC administrations. sNfL levels and clinical outcomes (relapses, MRI activity, EDSS score) were also evaluated. Mixed models for repeated measures were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 48 patients were included (4w: n=20; 6w: n=28). CD49d RO remained stable over time within both dosing schedules across all lymphocyte subsets. A significant difference between groups was observed only in CD19+ cells at the third administration (LS mean difference 13.08, SE\u00a0=\u00a04.10; p=0.028; 95% CI: 4.90\u201321.26) without clinical correlation. sNfL levels showed no significant differences at any timepoint within or between groups. Clinically, patients remained stable, with no new MRI activity or disability progression during the follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Switching from IV to SC NTZ while maintaining either standard (4w) or extended (6w) dosing intervals preserves pharmacodynamic stability, as reflected by sustained CD49d RO, stable sNfL levels, and consistent clinical outcomes. These findings support SC administration as a reliable alternative to IV NTZ, including in extended interval dosing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1879496","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:50:24Z","timestamp":1784695824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological and clinical stability after switching from intravenous to subcutaneous natalizumab in RRMS under standard and extended dosing"],"prefix":"10.3389","volume":"17","author":[{"given":"Alex","family":"Agundez-Moreno","sequence":"first","affiliation":[{"name":"Department of Immunology, Germans Trias i Pujol Research Institute and University Hospital","place":["Badalona, Spain"]},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Presas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital","place":["Badalona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Manuel","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital","place":["Badalona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina","family":"Teniente-Serra","sequence":"additional","affiliation":[{"name":"Department of Immunology, Germans Trias i Pujol Research Institute and University Hospital","place":["Badalona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Arcos-Ribas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Germans Trias i Pujol Research Institute and University Hospital","place":["Badalona, Spain"]},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Maria","family":"Mart\u00ednez-Caceres","sequence":"additional","affiliation":[{"name":"Department of Immunology, Germans Trias i Pujol Research Institute and University Hospital","place":["Badalona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Querol","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital de la Santa Creu i Sant Pau, IR SANT PAU","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Mart\u00edn-Aguilar","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital de la Santa Creu i Sant Pau, IR SANT PAU","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Vidal-Jordana","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital de la Santa Creu i Sant Pau, IR SANT PAU","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Meca Lallana","sequence":"additional","affiliation":[{"name":"Neurology, Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Virgen de la Arrixaca Clinical University Hospital","place":["Cartagena, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Dos-Santos","sequence":"additional","affiliation":[{"name":"Neurology, Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Virgen de la Arrixaca Clinical University Hospital","place":["Cartagena, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Millan","sequence":"additional","affiliation":[{"name":"Neurology, Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Virgen de la Arrixaca Clinical University Hospital","place":["Cartagena, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Valero","sequence":"additional","affiliation":[{"name":"Neurology, Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Virgen de la Arrixaca Clinical University Hospital","place":["Cartagena, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de Matar\u00f3","place":["Matar\u00f3, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Casado","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de Matar\u00f3","place":["Matar\u00f3, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuncia","family":"Boltes-Alandi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de Granollers","place":["Granollers, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Vicente","family":"Hervas-Garcia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Mois\u00e8s Broggi","place":["Sant Joan Desp\u00ed, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Brieva","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Arnau Vilanova","place":["Lleida, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Unit, Neurology Department, Hospital Josep Trueta","place":["Girona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ramo-Tello","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital","place":["Badalona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis - a review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur J Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0082-z","article-title":"Treatment of multiple sclerosis - success from bench to bedside","volume":"15","author":"Tintore","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13215","article-title":"Current and emerging disease-modulatory therapies 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Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1879496\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:50:31Z","timestamp":1784695831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1879496\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2026.1879496"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1879496","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1879496"}}