{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:20:53Z","timestamp":1791580853143,"version":"4.3.4"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>In the 2-year Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (ULTIMATE) I and II randomized clinical studies, disease activity was significantly reduced with ublituximab vs teriflunomide in participants with relapsing multiple sclerosis (RMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate long-term ublituximab clinical efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>The 2-year, multicenter, randomized, active-controlled, double-blind period (DBP) of the ULTIMATE I and II phase 3 studies occurred September 2017 to November 2020. Enrollment in the ongoing ULTIMATE open-label extension (OLE) study began November 2019; data cutoff for this analysis was January 1, 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>ULTIMATE OLE participants continued ublituximab (UBL-UBL) or switched from teriflunomide to ublituximab (TER-UBL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Efficacy (annualized relapse rate [ARR], 24-week confirmed disability progression [CDP24], and 24-week confirmed disability improvement [CDI24]) and safety were key outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 985 adults with RMS who completed ULTIMATE I and II, 851 enrolled in the ULTIMATE OLE and were included in the analysis. On DBP completion, more than 85% of participants (UBL-UBL, 422 of 494; TER-UBL, 429 of 491) entered the OLE, of whom more than 70% (UBL-UBL, 297 of 422; TER-UBL, 327 of 429) continued taking ublituximab at year 5 (OLE year 3) at data cutoff, making up the analysis population (mean [SD] age, 38.5 [9.7] years; 532 female [62.5%]). TER-UBL participants experienced a 58.4% ARR reduction at 1 year after the switch (0.182 vs 0.076; rate ratio, 0.42; 95% CI, 0.29-0.60;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), and ARR continued to decrease to 0.048 (year 4) and 0.045 (year 5). UBL-UBL participants had further ARR reductions after the DBP (0.053, 0.032, and 0.020 for years 3, 4, and 5, respectively). At year 5, CDP24 was 8.0% in UBL-UBL participants vs 14.3% in TER-UBL participants (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.01), and CDI24 was 17.0% in UBL-UBL participants vs 12.2% in TER-UBL participants (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.02). Adverse events were consistent with the established safety profile from pivotal trials, with exposure-adjusted incidence rates per 100 participant-years of serious infections (excluding COVID events) of 2.10 (UBL-UBL) and 2.58 (TER-UBL). On average, immunoglobulin levels remained above the lower limit of normal, and no significant differences in serious infection rates were observed regardless of immunoglobulin level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results reveal that sustained clinical benefits were observed with 5 years of ublituximab treatment: ARR in year 5 showed 1 relapse per 50 participant-years of ublituximab treatment and 92% of UBL-UBL participants remained free from CDP24. Results confirm long-term ublituximab benefits and early initiation of high-efficacy treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04130997\">NCT04130997<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.0007","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:30:30Z","timestamp":1771259430000},"page":"348","source":"Crossref","is-referenced-by-count":9,"title":["Five Years of Ublituximab in Multiple Sclerosis"],"prefix":"10.1001","volume":"83","author":[{"given":"Bruce A. 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