Therapeutic Advances in Neurological Disorders最新文献

{"title":"Neuroglial markers of damage in autoimmune neurology.","authors":"Alessandro Dinoto, Sara Mariotto","doi":"10.1177/17562864261433329","DOIUrl":"10.1177/17562864261433329","url":null,"abstract":"<p><p>The advancements in assays for the detection of neuroglial markers of damage, such as neurofilament light chain and glial fibrillary acid protein, have led to a growing interest in their investigation in neurological disorders. In this review, we aim to summarize evidence regarding the role of biomarkers of neuroglial damage in autoimmune neurological disorders of the central nervous system, including myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, autoimmune encephalitis, and paraneoplastic neurological syndromes. We will discuss how these biomarkers can help our understanding of disease mechanisms and how these results can be potentially translated into clinical practice, helping clinicians in the differential diagnosis, in prognostication, and prediction of the risk of relapse.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261433329"},"PeriodicalIF":4.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Delphi consensus on integrating novel therapies into the management of generalized myasthenia gravis.","authors":"John Vissing, Fritz Zimprich, Sari Atula, Andrew Chan, Henning Andersen, Raffi Topakian, Martijn R Tannemaat, Konrad P Weber, Hakan Cetin, Christoph Neuwirth, Hanna Kuusisto, Wolfgang N Loescher","doi":"10.1177/17562864261429176","DOIUrl":"10.1177/17562864261429176","url":null,"abstract":"<p><strong>Background: </strong>The treatment landscape for myasthenia gravis (MG) has evolved with the introduction of novel therapies. An international consensus on patient selection criteria and optimal time to initiate these therapies could improve clinical outcomes and reduce delays for likely beneficiaries.</p><p><strong>Objective: </strong>This Delphi consensus was undertaken by MG specialists from selected European countries to explore gaps in the application of national guidelines and elicit expert opinion in practice.</p><p><strong>Design: </strong>A mixed-method approach was used; qualitative and quantitative study phases were combined to explore key concepts and reach consensus.</p><p><strong>Methods: </strong>The qualitative first phase involved seven healthcare professionals (HCPs) and two patient advocacy group representatives who participated in idea generation. Findings from this phase supported the development of a Delphi survey, which was completed by 16 HCPs in two rounds. This constituted the quantitative second phase of the study. Consensus was defined as ⩾70% agreement or disagreement on a 6-point Likert scale.</p><p><strong>Results: </strong>In total, 65% of statements achieved consensus. Key findings include-HCPs highly regard international guidelines but find critical discrepancies between the \"ideal\" scenario and current clinical practices. Consensus was achieved on the importance of incorporating patient-related quality of life in decision-making, despite limited current methods. Consensus was obtained on steroid tapering and treatment-switch criteria based on steroid dose and duration. Consensus was also achieved on suitable patient profiles, including those with persistent symptoms, severe side effects, or needing rapid control.</p><p><strong>Conclusion: </strong>This study recognized that guidelines offer valuable direction but do not replace individualized treatment decisions. This study identified the areas of alignment and opportunities to refine patient selection criteria and treatment-switch categories, particularly to integrate novel therapy use in MG management, highlighting a path to a more patient-centric approach.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261429176"},"PeriodicalIF":4.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glymphatic dysfunction in drug-resistant epilepsy and its association with vagus nerve stimulation outcomes: a DTI-ALPS study.","authors":"Ziao Xu, Xiaofeng Wang, Bohang Liu, Xuefei Ji, Ming Shan, Hongwei Cheng, Lei Ye","doi":"10.1177/17562864261436543","DOIUrl":"10.1177/17562864261436543","url":null,"abstract":"<p><strong>Background: </strong>The glymphatic system (GS) is critical for interstitial fluid clearance and has been implicated in various neurological disorders. However, its role in drug-resistant epilepsy (DRE) and response to vagus nerve stimulation (VNS) remains unclear.</p><p><strong>Objectives: </strong>This study aimed to assess GS function in patients with DRE using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its association with VNS outcomes.</p><p><strong>Design: </strong>Data from patients with DRE who underwent VNS were retrospectively analyzed at a single center.</p><p><strong>Methods: </strong>Forty patients with DRE and 30 healthy controls were enrolled. ALPS indices were calculated for the left (ALPS-L), right (ALPS-R), and bilateral (ALPS-B) hemispheres. The clinical outcomes after VNS were classified using McHugh outcome classification. Statistical comparisons and logistic regression were used to examine group differences and the predictive value of ALPS indices.</p><p><strong>Results: </strong>Compared to controls, patients with DRE exhibited significantly reduced ALPS-L (<i>p</i> < 0.001) and ALPS-B (<i>p</i> = 0.005) indices. Among patients with DRE, responders to VNS had significantly higher ALPS-R (<i>p</i> = 0.021) and ALPS-B (<i>p</i> = 0.027) indices than nonresponders. ALPS-L exhibited a positive trend (<i>p</i> = 0.073). In logistic regression analyses, ALPS-R and ALPS-B were significantly associated with favorable VNS outcomes in univariate and multivariate models. After adjusting for age, sex, and disease duration, ALPS-L (<i>p</i> = 0.028, odds ratio (OR) = 2.739), ALPS-R (<i>p</i> = 0.020, OR = 2.802), and ALPS-B (<i>p</i> = 0.020, OR = 3.241) all emerged as independent predictors of VNS response.</p><p><strong>Conclusion: </strong>Glymphatic dysfunction is present in DRE and may influence responsiveness to VNS. Higher ALPS indices predicted better treatment outcomes, supporting ALPS potential as a noninvasive imaging biomarker for presurgical stratification in epilepsy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261436543"},"PeriodicalIF":4.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromyelitis optica spectrum disorders.","authors":"Mohammad Ali Sahraian, Kazuo Fujihara","doi":"10.1177/17562864261430493","DOIUrl":"10.1177/17562864261430493","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261430493"},"PeriodicalIF":4.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new, glycoengineered form of anti-CD20 monoclonal antibody, in treatment of multiple sclerosis.","authors":"Krzysztof Selmaj, Ralf Gold, Igor Selmaj, Marcin P Mycko","doi":"10.1177/17562864261434868","DOIUrl":"10.1177/17562864261434868","url":null,"abstract":"<p><p>B-cell depletion with anti-CD20 monoclonal antibody (mAb) represents a novel and highly effective treatment for patients with multiple sclerosis. Although all approved anti-CD-20 mAbs for multiple sclerosis (MS) treatment, ocrelizumab, ofatumumab, and ublituximab, target the same molecule on the B-cell surface, some differences in their molecular structure translate into important distinctions in their mechanisms of B-cell depletion. Differences between an antibody-dependent cell-mediated cytotoxicity (ADCC) versus a complement-dependent cytotoxicity (CDC) in anti-CD20 mAbs mechanism of action correspond to deeper B-cell depletion as well as better tolerability. Glycoengineering of the Fc portion of ublituximab with reduced fucosylation enhances affinity to Fc gamma receptor IIIa (FcγRIIIa) on natural killer (NK) cells. This molecular modification of ublituximab exhibits significantly higher ADCC activity in relation to CDC in B-cell depletion mechanisms. In addition, glycoengineering of ublituximab reduces the importance of the FcγRIIIa 158V/F polymorphism, which influences the effectiveness of B-cell depletion. In the ULTIMATE I and II studies, ublituximab showed a significant reduction in annual relapse rate versus teriflunomide in relapsing MS patients and strikingly reduced active and new/enlarging MRI lesions. Ublituximab also showed efficacy on the disease progression and increased disability improvement in the extended 5-year observation study. The advantage of ublituximab also correlates with good tolerability and reduced infusion-related reactions. Ublituximab infusion, 1 h, is significantly shorter in comparison to other intravenous (IV) preparations of anti-CD20 mAbs. Thus, ublituximab provides better convenience to MS patients as well as saves the time of healthcare providers.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261434868"},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of mechanical thrombectomy in acute stroke due to primary embolic middle cerebral artery M2 occlusions: a comparison of late versus early windows.","authors":"Huan Wang, Deren Wang, Elena Zapata-Arriaza, Marta Aguilar-Pérez, Asier de Albóniga-Chindurza, Henry Antonio Andrade Ruiz, Joan Montaner, Alejandro González García","doi":"10.1177/17562864261434562","DOIUrl":"10.1177/17562864261434562","url":null,"abstract":"<p><strong>Background: </strong>Current guidelines consider mechanical thrombectomy (MT) reasonable for M2 segment middle cerebral artery (MCA) occlusions within 6 h of symptom onset, yet the impact of delayed intervention in this population remains unclear.</p><p><strong>Objectives: </strong>This study compared effectiveness and safety outcomes of MT performed in late (>6 h) versus early (⩽6 h) treatment windows in patients with acute primary embolic M2 occlusions.</p><p><strong>Design: </strong>We retrospectively analyzed patients with primary embolic M2 occlusions treated with MT within 24 h of onset from the ARTISTA (A Registry for Thrombectomy In Stroke Therapy from Andalusia) registry (2017-2024) in Seville-Huelva, Spain.</p><p><strong>Methods: </strong>Outcomes compared between late and early treatment groups included good outcome (90-day modified Rankin Scale (mRS) 0-2 or return to prestroke mRS), futile recanalization (FR; 90-day mRS >2 despite successful recanalization), successful recanalization (modified Thrombolysis in Cerebral Infarction ⩾2b), and symptomatic intracranial hemorrhage (sICH). Multivariable logistic regression and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate associations between treatment window and MT outcomes.</p><p><strong>Results: </strong>Among 524 patients (median age 76, 48.3% women), 207 (39.5%) underwent MT in the late window. Late treatment showed numerically lower rates of good outcome (58.9% vs 64.4%) and higher rates of FR (37.8% vs 32.5%) and sICH (3.4% vs 3.2%), though none were statistically significant (all <i>p</i> ⩾0.211). Successful recanalization rates were nearly identical between the late and early windows (95.7% vs 95.6%; <i>p</i> = 0.970). IPTW-adjusted analyses also found no significant differences in good outcome (adjusted odds ratio (aOR), 0.82; 95% confidence interval (CI), 0.39-1.73; <i>p</i> = 0.600) or FR (aOR, 1.19; 95% CI, 0.56-2.50; <i>p</i> = 0.653) at 90 days.</p><p><strong>Conclusion: </strong>In this multicenter real-world cohort, MT performed beyond 6 h showed effectiveness and safety outcomes comparable to early-window intervention in patients with primary embolic MCA M2 occlusions.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261434562"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Economic value of anti-CD20 therapies in multiple sclerosis: a systematic review of cost-effectiveness studies.","authors":"Johannes Heinemann, Marco Zirkel, Oliver Schoeffski, Rick Dersch, Heinz Wiendl","doi":"10.1177/17562864261426816","DOIUrl":"10.1177/17562864261426816","url":null,"abstract":"<p><strong>Background: </strong>Disease-modifying therapies (DMTs) have transformed multiple sclerosis (MS) care but are associated with substantial costs. Among high-efficacy DMTs, anti-CD20 antibodies are widely used, yet their economic value, particularly compared with different classes of DMTs, has not been comprehensively synthesized.</p><p><strong>Objective: </strong>To systematically review evidence on the cost-effectiveness of anti-CD20 antibodies compared with other DMTs or best supportive care (BSC) in MS.</p><p><strong>Data sources and methods: </strong>We searched <i>PubMed</i>, <i>Embase</i>, <i>Web of Science</i>, and <i>International Network of Agencies for Health</i> Technology <i>Assessment</i> (July 2025) for cost-effectiveness analyses comparing rituximab, ocrelizumab, ofatumumab, or ublituximab with other DMTs or BSC. Two reviewers independently screened studies, extracted data, and assessed reporting quality using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. All costs were converted to 2024 US dollars and adjusted for inflation.</p><p><strong>Results: </strong>Of 92 records screened, 20 studies met inclusion criteria. Analyses were conducted in diverse but mostly high-income regions, most commonly using Markov models with long time horizons. Anti-CD20 antibodies were dominant (more effective, less costly) or cost-effective in the majority of studies, particularly when compared with platform therapies. In contrast, comparisons with other high-efficacy DMTs yielded more heterogeneous results, with immune reconstitution therapies more cost-effective in several studies. Reporting quality was generally high, although patient involvement, assessment of heterogeneity, and a health economic analysis plan were rarely addressed.</p><p><strong>Conclusion: </strong>These findings support the use of anti-CD20 antibodies as an economically reasonable option in many healthcare settings, particularly when compared with platform therapies, while underscoring that cost-effectiveness relative to other high-efficacy treatments is context-dependent. The lack of data from low- and middle-income countries and limited transparency in Health Technology Assessment reports represent major limitations. Future research should prioritize context-specific evaluations and promote full disclosure of economic data to strengthen the evidence base for clinically and economically informed reimbursement decisions in MS.</p><p><strong>Trial registration: </strong>The study was prospectively registered with PROSPERO (ID: CRD420251109958).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261426816"},"PeriodicalIF":4.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into adherence to cladribine tablets in the real world in multiple countries: results from patient support programs.","authors":"Jiwon Oh, Mavis Ayer, Raed Alroughani, Samar Farouk, Mounir Khoury, Sabrina de Souza, Michela Bossolasco, Kate Morgan, Laura Negrotto, Tracey Quinn, Amir Boshra, Joseph Youssef, Murad Al-Naqshbandi, Kelly MacDonald, Meritxell Sabidó, Jeffrey M Muir, Berenice Silva","doi":"10.1177/17562864261426842","DOIUrl":"10.1177/17562864261426842","url":null,"abstract":"<p><strong>Background: </strong>Patient support programs (PSP) help initiate and maintain disease-modifying treatment (DMT) for people with multiple sclerosis (PwMS). adveva^® (worldwide), Alcura Healthcare (Netherlands), and MS LifeLines^® (US) are nurse-pharmacy-led PSPs that collect clinical information, with consent, on PwMS receiving cladribine tablets (3.5 mg/kg over 2 years followed by a 2-year treatment-free period per product label).</p><p><strong>Objective: </strong>To evaluate initiation and completion of short courses of cladribine tablets treatment in Years 1 and 2 for PwMS and the frequency of subsequent treatment.</p><p><strong>Design: </strong>Retrospective, multinational, observational study using real-world data from PSPs.</p><p><strong>Methods: </strong>Clinical data from PSPs in Australia, Canada, Gulf, Latin America, Near East, Netherlands, UK, and US (December 2017-December 2023) included prior DMT use, cladribine tablets initiation and completion (Years 1 and 2), and subsequent treatment after Year 2 for those with ⩾48 months' follow-up.</p><p><strong>Results: </strong>Across all PSPs, 22,082 PwMS initiated cladribine tablets (Australia, <i>n</i> = 799; Canada, <i>n</i> = 3665; Gulf, <i>n</i> = 258; Latin America, <i>n</i> = 1854; Near East, <i>n</i> = 86; Netherlands, <i>n</i> = 681; UK, <i>n</i> = 2320; US, <i>n</i> = 12,418), of whom 70.9%-81.3% were female (mean age 34.2-49.1 years). Most were DMT-experienced (Australia, no contribution to analysis; Canada, 100%; Gulf, 52.7%; Latin America, 57.7%; Near East, 86.0%; Netherlands, 81.4%; UK, 30.0%; US, 79.5%) with oral DMTs most commonly used (36.5%-69.3%). In PwMS with ⩾18 months' follow-up, ⩾82.8% initiated Year 2 treatment at a mean of 12.4 (±3.8) to 13.9 (±3.5) months after initiating Year 1 treatment. Of those commencing Year 2 treatment, ⩾93.6% completed it. Additional treatment with cladribine tablets beyond 48 months was administered in a small proportion of PwMS: Canada, 5.6%; Latin America, 4.3%; Netherlands, 3.8%; and UK, 1.8%.</p><p><strong>Conclusion: </strong>Cladribine tablets adherence was high, with most PwMS completing short-course cladribine tablets treatment in Years 1 and 2. Of those with ⩾48 months' follow-up, only a small proportion received additional cladribine tablets treatment.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261426842"},"PeriodicalIF":4.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel homozygous <i>SYNE1</i> missense variant in late onset autosomal recessive cerebellar ataxia 1: a case report.","authors":"Igor Selmaj, Nastassja Himmelreich, Krzysztof Selmaj","doi":"10.1177/17562864261433620","DOIUrl":"10.1177/17562864261433620","url":null,"abstract":"<p><p>SYNE1 ataxia is a rare representative of autosomal recessive hereditary cerebellar ataxias (ARCAs). It was originally described in the Beauce region of Quebec as a pure cerebellar form of ataxia. Later, more complex phenotypes with a wide range of extra-cerebellar neurological and non-neurological dysfunctions were discovered in other geographical locations. SYNE1 deficiency was predominantly linked to nonsense and frameshift variants; however, missense variants in the gene <i>SYNE1</i> have also been described as causative for this type of ataxia. We here describe a case of an adult female patient with a phenotype of progressive ataxic features over 15 years, combined with spastic paraparesis. Non-neurological symptoms were not present. The family history was negative, and the case was classified as sporadic. However, the parents of the patient were related to both grandmothers, being cousins. DNA was sequenced using the Illumina HiSeq/Nova Seq system, and the variant c.23413A>G; p.Arg7805Gly in the gene <i>SYNE1</i> was found in a homozygous state (NM_033071.4; NP_149062.2). This missense variant has not been described in the literature and is not listed in the relevant databases. This homozygous substitution resulted in an amino acid change, arginine for glycine, in a highly conserved region of the <i>SYNE1</i> gene. According to ACMG/ACGS guidelines, the criteria PM2+PM3_supporting+PP3 were applied, which classified the substitution c.23413A>G; p.Arg7805Gly as \"a variant of uncertain significance.\" The calculated effect of this substitution is mostly pathogenic based on several in silico prediction programs. The presence of spastic paraparesis grades this case as an ataxic complex syndrome. This is the first SYNE1 ataxia patient of Polish origin with a novel missense variant described with full clinical and MRI data.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261433620"},"PeriodicalIF":4.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness of anti-CD20 therapies and S1P receptor modulators in late-onset multiple sclerosis: real-world evidence from the MSBase registry.","authors":"Andrea Surcinelli, Tomas Kalincik, Izanne Roos, Emanuele D'Amico, Jeannette Lechner-Scott, Serkan Ozakbas, Pavel Hradilek, Dana Horáková, Marta Vachova, Ivan Panzera, Stefano Ruzza, Maria Grazia Piscaglia, Oliver Gerlach, Jose Eustasio Meca-Lallana, Gabriel Valero-López, Allan G Kermode, Marzena J Fabis-Pedrini, Julie Prevost, Radek Ampapa, Suzanne Hodgkinson, Francois Grand'Maison, Samia J Khoury, Nevin A John, Marek Peterka, Jana Houskova, Eva Recmanova, Zuzana Rous, Vahid Shaygannejad, Raed Alroughani, Jens Kuhle, Gregor Brecl Jakob, Pierre Grammond, Francesco Patti, Anneke Van der Walt, Helmut Butzkueven, Matteo Foschi","doi":"10.1177/17562864261430084","DOIUrl":"10.1177/17562864261430084","url":null,"abstract":"<p><strong>Background: </strong>Late-onset multiple sclerosis (LOMS), defined by symptom onset after age 50, is increasingly recognised as a distinct clinical entity. Evidence comparing disease-modifying therapies (DMTs) in this subgroup remains limited.</p><p><strong>Objectives: </strong>To compare clinical outcomes of anti-CD20 monoclonal antibodies and sphingosine-1-phosphate receptor modulators (S1PRMs) in LOMS.</p><p><strong>Design: </strong>Multicentre, observational cohort study based on real-world data from an international multiple sclerosis registry.</p><p><strong>Methods: </strong>We analysed data from the MSBase registry, including relapsing-remitting LOMS patients treated with anti-CD20 therapies (ocrelizumab, ofatumumab, rituximab) or S1PRMs (fingolimod, ozanimod, siponimod, ponesimod) for ⩾6 months. Primary outcomes were annualised relapse rate (ARR), Expanded Disability Status Scale (EDSS) change, confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), and PIRA without MRI activity (PIRMA). Analyses used inverse probability of treatment weighting (IPTW). Causal forest and best linear projector (BLP) models explored effect modification.</p><p><strong>Results: </strong>After weighting, 347 patients (median age 53.7 years; 69% female; median follow-up 6.9 years) were included. No significant differences were found for ARR, EDSS change, CDW, PIRA, or PIRMA. Exploratory analyses suggested greater anti-CD20 benefit in patients with earlier onset (⩽55 years), shorter disease duration (⩽2 years from diagnosis), and lower disability (EDSS < 3).</p><p><strong>Conclusions: </strong>In this real-world LOMS cohort, no statistically significant differences were observed between anti-CD20 and S1PRM therapies. Exploratory analyses suggested anti-CD20 may be associated with better outcomes in selected subgroups; these findings are hypothesis-generating.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261430084"},"PeriodicalIF":4.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}