{"id":1994,"date":"2026-05-12T07:20:02","date_gmt":"2026-05-12T07:20:02","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/12\/most-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses\/"},"modified":"2026-05-12T07:20:02","modified_gmt":"2026-05-12T07:20:02","slug":"most-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/12\/most-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses\/","title":{"rendered":"Most of progression is due to the effects of lesions controlled by drugs that inhibit relapses"},"content":{"rendered":"<div class=\"twitter-share\"><a href=\"https:\/\/twitter.com\/intent\/tweet?url=https%3A%2F%2Fmultiple-sclerosis-research.org%2F2026%2F05%2Fmost-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses%2F&#038;via=the_MSBlog\" class=\"twitter-share-button\" data-size=\"large\">Tweet<\/a><\/div>\n<p>Signori A, Montobbio N, Bovis F, Ponzano M, Schiavetti I, Krenn A, Sormani MP. Uncoupling Relapse Reduction and Disability Progression: Evidence From Tolebrutinib Studies. Neurol Clin Pract. 2026; 16:e200612.<\/p>\n<p><strong>Objectives:\u00a0<\/strong>The aim of this study was to evaluate whether the treatment effects of tolebrutinib on confirmed disability worsening (CDW) diverge from its effects on relapse prevention compared with other disease-modifying therapies (DMTs) for relapsing multiple sclerosis (MS).<\/p>\n<p><strong>Methods:&nbsp;<\/strong>We extracted published effect estimates for annualized relapse rate (ARR) and CDW confirmed at 24 weeks from all phase 3 trials with teriflunomide as the active comparator: ASCLEPIOS (ofatumumab), OPTIMUM (ponesimod), ULTIMATE (ublituximab), EVOLUTION (evobrutinib), and GEMINI (tolebrutinib). When duplicate trials were available, pooled estimates were derived. Log-transformed estimates were used in a weighted linear regression of CDW vs ARR, with bubble size reflecting statistical precision. Tolebrutinib was excluded from the regression fit but displayed for comparison.<\/p>\n<p><strong>Results:\u00a0<\/strong>Across 4 DMTs other than tolebrutinib, <strong>a strong linear association was observed between treatment effects on ARR and CDW (R<sup>2<\/sup>\u00a0= 0.997)<\/strong> S<em>o this says that in most studies that progression is associated with lesional\/relapse activity<\/em> a<em>nd so the concept of PIRA after drugs like anti-CD20 is all tosh as I have been saying for years because progression is inter related to events associated with diseae activity<\/em>,, indicating that disability benefit was generally proportional to relapse reduction. <em>This not surprising because the drugs don&#8217;t really get into the brain and so again the CNS&#8230;.Why have the great and the good not got this?&#8230;.Maybe good that I was put out to grass. <\/em> By contrast, tolebrutinib deviated from this relationship, with a hazard ratio for CDW of 0.71 (95% CI 0.53-0.95) despite a relapse rate ratio of 1.03 (95% CI 0.85-1.25).<\/p>\n<p><strong>Discussion:&nbsp;<\/strong>Tolebrutinib was the only therapy to show a benefit on CDW without a measurable effect on relapses, highlighting a dissociation between disability worsening and relapse suppression not observed with other DMTs.<\/p>\n<p><em>So tolebrutinib should be given to people on something elses that controls relapses<\/em>. Shame the FDA didn&#8217;t buy the Idea but the EMA in Europe did.<\/p>\n<p><em>Source: <a href=\"https:\/\/multiple-sclerosis-research.org\/2026\/05\/most-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses\/?utm_source=rss&#038;utm_medium=rss&#038;utm_campaign=most-of-progression-is-due-to-the-effects-of-lesions-controlled-by-drugs-that-inhibit-relapses\" rel=\"nofollow noopener\" target=\"_blank\">multiple-sclerosis-research.org<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tweet Signori A, Montobbio N, Bovis F, Ponzano M, Schiavetti I, Krenn A, Sormani MP. Uncoupling Relapse Reduction and Disability Progression: Evidence From Tolebrutinib Studies. Neurol Clin Pract. 2026; 16:e200612. Objectives:\u00a0The aim of this study was to evaluate whether the treatment effects of tolebrutinib on&hellip;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[11,15,9,8,13,14,12,10],"class_list":["post-1994","post","type-post","status-publish","format-standard","hentry","category-multiple-sclerosis-research","tag-brain-repair","tag-marburg-type-ms","tag-ms","tag-multiple-sclerosis","tag-myelin","tag-neuroregeneration","tag-oligodendrocyte","tag-remyelination"],"_links":{"self":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/1994","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/comments?post=1994"}],"version-history":[{"count":0,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/1994\/revisions"}],"wp:attachment":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media?parent=1994"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/categories?post=1994"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/tags?post=1994"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}