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Anti-drug antibody responses may limit drug efficacy, but current guidance recommends anti-drug antibody testing only after evidence of \u2018reduced efficacy\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess the lack of relative lymphocytosis as a biomarker of anti-drug antibody responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Lymphocyte counts and immunogenicity data from the pivotal AFFIRM clinical trial (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009627 natalizumab vs\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009315 placebo) and real-world data from the Cardiff MS register (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009185) were analysed to assess the relationship between lymphocyte counts, anti-drug antibody responses, drug levels and disease activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Natalizumab treatment induced an absolute change in lymphocyte counts by week 12 (1.40\u2009\u00b1\u20090.92 vs \u22120.05\u2009\u00b1\u20090.62\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      cells\/L in natalizumab vs placebo;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) that was absent in the persistent anti-drug antibody group (\u22120.12\u2009\u00b1\u20090.60 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      cells\/L). Increases in lymphocyte counts by\u2009\u2a7e\u20090.8 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      cells\/L from the baseline discriminated individuals without anti-drug antibody responses with high sensitivity (\u2265\u200984%) and specificity (\u2265\u200991%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The absence of relative lymphocytosis is associated with anti-drug antibody responses and may provide a simple biomarker to prompt anti-drug antibody testing before disease breakthrough occurs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261495351","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:58:42Z","timestamp":1792231122000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lymphocytosis as a biomarker for natalizumab treatment response in multiple sclerosis: The link with anti-drug antibodies"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6311-3870","authenticated-orcid":false,"given":"Ester","family":"Valero-Hernandez","sequence":"first","affiliation":[{"name":"Blizard Institute, Queen Mary University of London, UK"},{"name":"Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Queen Mary University of London, UK"},{"name":"Centre for Oral Immunobiology and Regenerative Medicine, Blizard Institute, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai","family":"Mathur","sequence":"additional","affiliation":[{"name":"Swansea Bay University Health Board, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Baker","sequence":"additional","affiliation":[{"name":"Blizard Institute, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris Y. 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