{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:16:30Z","timestamp":1783426590207,"version":"3.54.6"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","msard-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis and Related Disorders"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.msard.2026.107334","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T05:27:06Z","timestamp":1782019626000},"page":"107334","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Taking progressive biology seriously in the time of B-cells and BTK"],"prefix":"10.1016","volume":"112","author":[{"given":"Carlos R.","family":"Camara-Lemarroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.msard.2026.107334_bib1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1177\/13524585241310764","article-title":"Paramagnetic rim lesion formation is predicted by the initial gadolinium-enhancing lesion diameter","volume":"31","author":"Al Gburi","year":"2025","journal-title":"Mult. Scler."},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/ana.25323","article-title":"Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas","volume":"84","author":"Bovis","year":"2018","journal-title":"Ann. Neurol."},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib3","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210142","article-title":"Long-term treatment with ocrelizumab in patients with early-stage relapsing ms: nine-year data from the opera studies open-label extension","volume":"104","author":"Cerqueira","year":"2025","journal-title":"Neurology"},{"issue":"12","key":"10.1016\/j.msard.2026.107334_bib4","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S1474-4422(25)00249-2","article-title":"Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications","volume":"24","author":"Chitnis","year":"2025","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.msard.2026.107334_bib5","unstructured":"ClinicalTrials.gov identifier: NCT040544449. U.S. National Library of Medicine, 2026. A Study to Evaluate the Efficacy and Safety ofFenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis (FENtrepid) [WWW Document]. ClinicalTrials.gov. URL https:\/\/clinicaltrials.gov\/study\/NCT04035005 (Accessed Feb 25, 2026)."},{"issue":"8","key":"10.1016\/j.msard.2026.107334_bib7","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1111\/ene.15862","article-title":"Association between age and inflammatory disease activity on magnetic resonance imaging in relapse onset multiple sclerosis during long-term follow-up","volume":"30","author":"Coerver","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"10.1016\/j.msard.2026.107334_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.msard.2024.106123","article-title":"Long-term effectiveness of cladribine tablets over 4 years in relapsing multiple sclerosis: results from the MAGNIFY-MS extension study","volume":"92","author":"De Stefano","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"issue":"19","key":"10.1016\/j.msard.2026.107334_bib11","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1056\/NEJMoa2415988","article-title":"HERCULES trial group. tolebrutinib in nonrelapsing secondary progressive multiple sclerosis","volume":"392","author":"Fox","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.msard.2026.107334_bib12","unstructured":"Fox R.J., et al., Efficacy of tolebrutinib in nonrelapsing secondary progressive multiple sclerosis (nrSPMS): subgroup analyses from the phase 3 HERCULES trial. In: ECTRIMS 2025: 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 2025b Sep 17-19; Barcelona, Spain. Abstract P796. [accessed Feb 25, 2026] Available from: congrex.com.."},{"key":"10.1016\/j.msard.2026.107334_bib13","unstructured":"Genetech, 2026. Genentech. Genentech's fenebrutinib is the first investigational medicine in over a decade to reduce disability progression in primary progressive multiple sclerosis [Internet]. South San Francisco (CA): Genentech; 2026 Feb 7 [Accessed Feb 25, 2026]. Available from: gene.com."},{"issue":"10544","key":"10.1016\/j.msard.2026.107334_bib14","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(26)00617-3","article-title":"Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis, including older patients and those with more advanced disease (ORATORIO-HAND): a multicentre, double-blind, randomised, placebo-controlled, phase 3b study","volume":"407","author":"Giovannoni","year":"2026","journal-title":"Lancet"},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib16","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/ana.21867","article-title":"OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial","volume":"66","author":"Hawker","year":"2009","journal-title":"Ann. Neurol."},{"issue":"5","key":"10.1016\/j.msard.2026.107334_bib17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1474-4422(18)30069-3","article-title":"ASCEND investigators. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension","volume":"17","author":"Kapoor","year":"2018","journal-title":"Lancet Neurol."},{"issue":"11","key":"10.1016\/j.msard.2026.107334_bib18","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1212\/WNL.57.11.1969","article-title":"European study group in interferon beta-1b in secondary-progressive MS. final analysis of the european multicenter trial on ifnbeta-1b in secondary-progressive MS","volume":"57","author":"Kappos","year":"2001","journal-title":"Neurology"},{"issue":"10","key":"10.1016\/j.msard.2026.107334_bib19","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1212\/01.WNL.0000145561.08973.4F","volume":"63","author":"Kappos","year":"2004","journal-title":"Neurology"},{"key":"10.1016\/j.msard.2026.107334_bib20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1136\/jnnp-2025-337940","article-title":"Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis","volume":"97","author":"Koch","year":"2026","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1177\/13524585211031801","article-title":"MRI brain volume loss, lesion burden, and clinical outcome in secondary progressive multiple sclerosis","volume":"28","author":"Koch","year":"2022","journal-title":"Mult. Scler."},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib22","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1177\/1352458515594440","article-title":"European Long-term Follow-up Study Group in Interferon \u03b2-1b in Secondary-progressive Multiple Sclerosis. A 10-year follow-up of the European multicenter trial of interferon \u03b2-1b in secondary-progressive multiple sclerosis","volume":"22","author":"Kuhle","year":"2016","journal-title":"Mult. Scler."},{"issue":"4","key":"10.1016\/j.msard.2026.107334_bib23","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/jnnp-2012-303291","article-title":"Interferon \u03b2 for secondary progressive multiple sclerosis: a systematic review","volume":"84","author":"La Mantia","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"issue":"2","key":"10.1016\/j.msard.2026.107334_bib24","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000214473","article-title":"Comparative effectiveness of rituximab dosed every 6 and 12 months in relapsing multiple sclerosis","volume":"106","author":"Langer-Gould","year":"2026","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.msard.2026.107334_bib25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1606468","article-title":"ORATORIO clinical investigators. ocrelizumab versus placebo in primary progressive multiple sclerosis","volume":"376","author":"Montalban","year":"2017","journal-title":"N. Engl. J. Med."},{"issue":"10","key":"10.1016\/j.msard.2026.107334_bib26","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1001\/jamaneurol.2025.2565","article-title":"Modulation of treatment effect on disability by disease activity in progressive multiple sclerosis: an individual patient data meta-analysis","volume":"82","author":"Montobbio","year":"2025","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.msard.2026.107334_bib27","unstructured":"Neuro-sens: ACTRIMS Forum 2026 Highlights: Tuesday, February 10, 2026 [Internet]. Montreal: Neuro-Sens; Feb 10 [Accessed Feb 25, 2026]. Available from neuro.sens.com."},{"issue":"2","key":"10.1016\/j.msard.2026.107334_bib28","doi-asserted-by":"crossref","DOI":"10.1136\/bmjno-2025-001126","article-title":"Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry","volume":"7","author":"Nguyen","year":"2025","journal-title":"BMJ Neurol. Open."},{"issue":"2","key":"10.1016\/j.msard.2026.107334_bib29","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/acn3.52253","article-title":"Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis","volume":"12","author":"Reeves","year":"2025","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.msard.2026.107334_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.msard.2025.106878","article-title":"Recommendations for the use of off-label rituximab for the treatment of multiple sclerosis in low-resource settings","volume":"105","author":"Rijke","year":"2026","journal-title":"Mult. Scler. Relat. Disord."},{"key":"10.1016\/j.msard.2026.107334_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.msard.2025.106858","article-title":"Non-inferiority of Rituximab versus OCrelizumab in Multiple Sclerosis (ROC-MS)-an individual participant data meta-analysis","volume":"105","author":"Schoof","year":"2026","journal-title":"Mult. Scler. Relat. Disord."},{"key":"10.1016\/j.msard.2026.107334_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.msard.2026.106974","article-title":"Efficacy and safety of bruton's tyrosine kinase inhibitors compared to teriflunomide in relapsing multiple sclerosis: a systematic review and meta-analysis","volume":"107","author":"Sobral","year":"2026","journal-title":"Mult. Scler. Relat. Disord."},{"issue":"7","key":"10.1016\/j.msard.2026.107334_bib33","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S1474-4422(13)70103-0","article-title":"MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials","volume":"12","author":"Sormani","year":"2013","journal-title":"Lancet Neurol."},{"issue":"10","key":"10.1016\/j.msard.2026.107334_bib34","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1136\/jnnp-2022-330887","article-title":"Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis","volume":"94","author":"Strijbis","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"issue":"2","key":"10.1016\/j.msard.2026.107334_bib35","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210153","article-title":"Utility of Progression Independent of Relapse Activity as a Trial Outcome in Relapsing-Remitting Multiple Sclerosis","volume":"104","author":"Strijbis","year":"2025","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.msard.2026.107334_bib36","doi-asserted-by":"crossref","DOI":"10.1148\/radiol.243718","article-title":"Prevalence and incidence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis","volume":"316","author":"Tranfa","year":"2025","journal-title":"Radiology"},{"issue":"2","key":"10.1016\/j.msard.2026.107334_bib37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s40268-024-00468-4","article-title":"Comparative cns pharmacology of the bruton's tyrosine kinase (BTK) inhibitor tolebrutinib versus other BTK inhibitor candidates for treating multiple sclerosis","volume":"24","author":"Turner","year":"2024","journal-title":"Drugs R. D."},{"key":"10.1016\/j.msard.2026.107334_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2025.1595929","article-title":"Progression independent of relapsing biology in multiple sclerosis: a real-word study","volume":"16","author":"Yong","year":"2025","journal-title":"Front. Neurol."}],"container-title":["Multiple Sclerosis and Related Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211034826003706?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211034826003706?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:34:37Z","timestamp":1783424077000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211034826003706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":34,"alternative-id":["S2211034826003706"],"URL":"https:\/\/doi.org\/10.1016\/j.msard.2026.107334","relation":{},"ISSN":["2211-0348"],"issn-type":[{"value":"2211-0348","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Taking progressive biology seriously in the time of B-cells and BTK","name":"articletitle","label":"Article Title"},{"value":"Multiple Sclerosis and Related Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.msard.2026.107334","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"simple-article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"107334"}}