{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:08:23Z","timestamp":1792706903467,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early high-efficacy treatment for people with relapsing multiple sclerosis (pwRMS) may provide better long-term outcomes compared with the escalation strategy. In this study, we present an analysis of treatment success and safety from the CONFIDENCE study in a real-world cohort of pwRMS treated with ocrelizumab in different treatment lines for up to 5.5\u202fyears.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The ongoing German non-interventional post-authorization safety study, CONFIDENCE (ML39632, EUPAS22951), evaluates the long-term safety and effectiveness of therapy in pwMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10\u202fyears. This analysis presents CONFIDENCE treatment success (proportion of people with no clinical disease activity measured by relapse or disease progression and no treatment discontinuation due to adverse event [AE] or lack of therapeutic effectiveness), confirmed disability progression (CDP), annualized relapse rates, and safety in pwRMS stratified by the number of previous MS therapies (PMSTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At the data cutoff (11 October 2023), the full analysis set included 2,261 pwRMS treated with \u22651 dose of ocrelizumab. At baseline, the mean age (SD) of the participants was 41.16 (11.39) years (treatment-na\u00efve, 39.19 [12.95] years; \u22653 PMSTs, 42.80 [10.08] years), and the mean Expanded Disability Status Scale (EDSS) score was 3.08 (1.86) (treatment-na\u00efve, 2.37 [1.54]; \u22653 PMSTs, 3.57 [1.90]). Overall, 58.4% of pwRMS with continuous treatment achieved CONFIDENCE treatment success from baseline until year 5 (74.0 and 50.3% of pwRMS with 0 and \u22653 PMSTs). The main reasons for not achieving CONFIDENCE treatment success were relapse and CDP, while treatment discontinuation due to AEs or lack of effectiveness played a minor role. The proportion of pwRMS with AEs did not increase with longer treatment duration and tended to be higher with more PMSTs. The spectrum of AEs was similar across treatment lines, and no new or unexpected AEs were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CONFIDENCE treatment success remained high over 5\u202fyears of ocrelizumab treatment, even among people with RMS (pwRMS) with a higher number of PMSTs. Only a small proportion of pwRMS discontinued treatment due to AEs. These results support early intervention with high-efficacy ocrelizumab treatment to optimize long-term outcomes for pwRMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/catalogues.ema.europa.eu\/node\/3142\/administrative-details<\/jats:uri>\n                      , identifiers ML39632 and EUPAS22951.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1564327","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T11:19:13Z","timestamp":1747826353000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["CONFIDENCE treatment success: long-term real-world effectiveness and safety of ocrelizumab in Germany"],"prefix":"10.3389","volume":"16","author":[{"given":"Mathias","family":"Buttmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bl\u00fcmich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hieke-Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Dirks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius C.","family":"Eggebrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjalf","family":"Ziemssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: the 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus interferon Beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"5124","DOI":"10.1212\/WNL.0000000000205584","article-title":"10 years of Ocrelizumab treatment in multiple sclerosis: long-term efficacy and safety clinical trial data (S31.005)","volume":"102","author":"Hauser","year":"2024","journal-title":"Neurology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e1854","DOI":"10.1212\/WNL.0000000000010376","article-title":"Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension","volume":"95","author":"Hauser","year":"2020","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1007\/s13311-021-01104-8","article-title":"Predictors of Ocrelizumab effectiveness in patients with multiple sclerosis","volume":"18","author":"Cellerino","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.3390\/jcm11082081","article-title":"Prognostic markers of Ocrelizumab effectiveness in multiple sclerosis: a real world observational multicenter study","volume":"11","author":"Lanzillo","year":"2022","journal-title":"J Clin Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1177\/13524585231196192","article-title":"Real-world safety data from up to 4.5 years of ocrelizumab in relapsing and primary progressive multiple sclerosis - a CONFIDENCE interim analysis. 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