{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:58:27Z","timestamp":1788519507450,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"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>The Norwegian guideline recommends highly effective disease-modifying therapies (DMTs) as the first line treatment for multiple sclerosis (MS), with rituximab preferred in clinical practice. While rituximab is effective, patients may discontinue due to side-effects or develop disease activity. Limited guidance exists on optimal switches following first line rituximab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To estimate the costs and effects of different treatment sequences following first line rituximab in relapsing remitting MS patients in Norway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A microsimulation model adapted to the Norwegian setting estimated outcomes for different treatment sequences following first line rituximab. Four neurologists were interviewed using a structured expert elicitation tool to inform switching behavior. The model allowed for three treatment lines after rituximab, with switches possible to fingolimod, ponesimod, cladribine tablets, or natalizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The model simulated all 32 possible treatment sequences and calculated costs per quality adjusted life year (QALY) according to Norwegian pharmacoeconomic guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Neurologists were more likely to switch patients with &amp;gt;1 relapse (78%) or relapse and disability progression (66%) versus one relapse (54%). The most cost-effective sequence after rituximab is cladribine tablets (line 2), ponesimod (line 3), and natalizumab (line 4). The probability that second line cladribine tablets are most cost-effective is &amp;gt;75%. Mean time on first line rituximab was 15.2\u202fyears. The model predicts that over lifetime 21% of patients would require a fourth line of treatment due to the cumulative effects of discontinuation and recurring disease activity triggering treatment switches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients on first line rituximab may require a treatment switch due to side-effect induced discontinuation or new disease activity. If a switch from rituximab to another DMT is the preferred clinical course of action, this study showed that it is most cost-effective to switch to cladribine tablets followed by ponesimod and natalizumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1783506","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:38:29Z","timestamp":1773812309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cost-effectiveness of treatment sequences following first-line rituximab in relapsing-remitting multiple sclerosis: a Norwegian microsimulation study"],"prefix":"10.3389","volume":"17","author":[{"given":"Simone","family":"Huygens","sequence":"first","affiliation":[{"name":"Huygens and Versteegh B.V.","place":["Zwijndrecht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Versteegh","sequence":"additional","affiliation":[{"name":"Huygens and Versteegh B.V.","place":["Zwijndrecht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"Berg-Hansen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein Henry","family":"Bjelland","sequence":"additional","affiliation":[{"name":"Vestfold Hospital Trust","place":["Vestfold, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trygve","family":"Holm\u00f8y","sequence":"additional","affiliation":[{"name":"Akershus University Hospital","place":["Akershus, Norway"]},{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ivind","family":"Torkildsen","sequence":"additional","affiliation":[{"name":"Neuro-SysMed, Department of Neurology, Haukeland University Hospital","place":["Bergen, Norway"]},{"name":"Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref1","year":"2025"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S1474-4422(22)00209-5","article-title":"Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial","volume":"21","author":"Svenningsson","year":"2022","journal-title":"Lancet 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