{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:06:43Z","timestamp":1780038403876,"version":"3.53.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013252","name":"TG Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence suggests that treating relapsing multiple sclerosis (RMS) initially with a high-efficacy disease-modifying therapy (DMT) is superior to an escalating approach at reducing disability progression and relapse rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the efficacy of ublituximab versus teriflunomide in participants without prior DMT (treatment-na\u00efve population) and in a subset of treatment-na\u00efve participants with symptom onset \u2264 three years (early treatment subpopulation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pooled\n                      <jats:italic>post hoc<\/jats:italic>\n                      analyses of ULTIMATE I\/II were conducted at Week 96.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The annualized relapse rate was 0.081 for ublituximab (\n                      <jats:italic>n<\/jats:italic>\n                      =\u00a0345) versus 0.188 for teriflunomide (\n                      <jats:italic>n<\/jats:italic>\n                      =\u00a0377) (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt;\u00a00.001) in the treatment-na\u00efve population and 0.130 for ublituximab (\n                      <jats:italic>n<\/jats:italic>\n                      =\u00a0139) versus 0.334 for teriflunomide (\n                      <jats:italic>n<\/jats:italic>\n                      =\u00a0140) in the early treatment subpopulation (\n                      <jats:italic>p<\/jats:italic>\n                      =\u00a00.004). Twelve-week confirmed disability improvement rates were 10.7% versus 5.3% (\n                      <jats:italic>p<\/jats:italic>\n                      =\u00a00.010) in the treatment-na\u00efve population and 14.4% versus 3.6% (\n                      <jats:italic>p<\/jats:italic>\n                      =\u00a00.002) in the early treatment population (ublituximab vs. teriflunomide). Significant reductions in gadolinium-enhancing T1 lesions and new\/enlarging T2 lesions, respectively, occurred for ublituximab versus teriflunomide (treatment na\u00efve: 0.031 vs. 0.791 and 0.390 vs. 4.144;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001 for both; early treatment: 0.051 vs. 1.030 and 0.508 vs. 6.068;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001 for both).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ublituximab was associated with significant treatment benefits at Week 96 in treatment-na\u00efve participants and those receiving treatment within three years of symptom onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT03277261<\/jats:ext-link>\n                      and\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT03277248<\/jats:ext-link>\n                      , identifiers NCT03277261 and NCT03277248.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1771848","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:57:00Z","timestamp":1780037820000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease outcomes with ublituximab in treatment-na\u00efve participants: subpopulation analyses of the phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Derrick","family":"Robertson","sequence":"first","affiliation":[{"name":"University of South Florida","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Alvarez","sequence":"additional","affiliation":[{"name":"University of Colorado","place":["Aurora, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Steinman","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[{"name":"Heinrich Heine University D\u00fcsseldorf","place":["D\u00fcsseldorf, Germany"]},{"name":"Brain and Mind Centre, University of Sydney","place":["Sydney, Australia"]},{"name":"Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Palack\u00fd University Olomouc","place":["Olomouc, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqing","family":"Qian","sequence":"additional","affiliation":[{"name":"Swedish Medical Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Selmaj","sequence":"additional","affiliation":[{"name":"Center of Neurology","place":["Lodz, Poland"]},{"name":"University of Warmia and Mazury","place":["Olsztyn, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibyl","family":"Wray","sequence":"additional","affiliation":[{"name":"Hope Neurology","place":["Knoxville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Wynn","sequence":"additional","affiliation":[{"name":"Consultants in Neurology","place":["Northbrook, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Fox","sequence":"additional","affiliation":[{"name":"TG Therapeutics","place":["Morrisville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koby","family":"Mok","sequence":"additional","affiliation":[{"name":"TG Therapeutics","place":["Morrisville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari P.","family":"Miskin","sequence":"additional","affiliation":[{"name":"TG Therapeutics","place":["Morrisville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihuan","family":"Xu","sequence":"additional","affiliation":[{"name":"TG Therapeutics","place":["Morrisville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Garner","sequence":"additional","affiliation":[{"name":"TG Therapeutics","place":["Morrisville, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A. 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