Neurology and Therapy最新文献

{"title":"Real-World Safety and Effectiveness of 24-Hour Foslevodopa/Foscarbidopa in Parkinson's Disease: ROSSINI Study 6-Month Interim Results.","authors":"Wolfgang H Jost, Filip Bergquist, Andrew Evans, Sharon Hassin-Baer, Robert A Hauser, Tove Henriksen, Irene A Malaty, Tiago A Mestre, Pablo Mir, Ramon Rodriguez, Petra Schwingenschuh, Mihaela Simu, Lars Bergmann, Teresa T Zhou, Sarah Caughlin, Mallika Gopalkrishnan, Pavnit Kukreja, Marie O'Meara, Juan Carlos Parra, Megha B Shah, Jason Aldred","doi":"10.1007/s40120-026-00948-6","DOIUrl":"https://doi.org/10.1007/s40120-026-00948-6","url":null,"abstract":"<p><strong>Introduction: </strong>Foslevodopa/foscarbidopa (LDp/CDp) is a nonsurgical 24-h continuous subcutaneous infusion for patients with advanced Parkinson's disease (aPD) and motor fluctuations uncontrolled on oral medications. We present the first multicountry real-world data from routine clinical practice.</p><p><strong>Methods: </strong>ROSSINI (NCT06107426) is an ongoing 3-year multicountry, prospective, observational study of adults with aPD who are LDp/CDp-naïve (cohort A) or transitioning from LDp/CDp open-label extension studies (NCT04379050/NCT04750226, cohort B). For this interim analysis, the primary endpoint was change from baseline to 6 months in OFF time [Movement Disorder Society Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) modified item 4.3]. Safety was assessed by monitoring adverse events (AEs). Interim results for 105 cohort A patients enrolled ≥ 6 months by March 24, 2025 are presented only; cohort B results were limited (n = 5). Mixed-effects models for repeated measurements (continuous outcomes) were utilized, adjusted for country.</p><p><strong>Results: </strong>Cohort A patients had a mean (SD) age of 68.5 (9.5) years, PD duration of 12.1 (5.3) years, and least squares mean (SE) OFF time of 5.2 (0.6) h at baseline. Patients on LDp/CDp showed statistically significant reductions (95% CI) in OFF time [(- 2.8 h (- 3.6, - 1.9), P ≤ .001, n = 47/40 at baseline/month 6], dyskinesia time [- 1.8 h (- 2.6, - 0.9), P ≤ 0.001], MDS-UPDRS-III [- 5.0 (- 8.2, - 1.9), P = 0.002], Parkinson's Disease Sleep Scale-2 [- 5.2 (- 8.0, - 2.4), P ≤ .001], and 39-item Parkinson's Disease Questionnaire [PDQ-39, - 5.6 (- 9.2, - 2.0), P = .002] from baseline to month 6. Freezing of Gait Questionnaire, Gastrointestinal Dysfunction Scale in PD, and King's PD Pain Scale likewise showed statistically significant decreases (P < .05). Overall, 58 (55.2%) reported ≥ 1 AE, primarily nonserious and mild-to-moderate (12.4% serious, 17.1% severe), with hallucinations and infusion site events the most frequently reported events (5.7% each).</p><p><strong>Conclusions: </strong>ROSSINI demonstrates reductions in motor fluctuations and nonmotor symptoms, and increased quality of life in patients with aPD after 6 months of LDp/CDp treatment. The safety profile was consistent with clinical trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT06107426.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence, Persistence, and Safety of Risdiplam in Spinal Muscular Atrophy: A Population-Based Cohort Study.","authors":"Maria Chovi-Trull, Nancy C Ñungo-Garzón, Karolina A Aragon-Gawinska, Inmaculada Pitarch-Castellano, Asunción Albert-Marí, Javier García-Pellicer, José L Poveda-Andrés, María D Edo-Solsona, Juan F Vázquez-Costa","doi":"10.1007/s40120-026-00947-7","DOIUrl":"https://doi.org/10.1007/s40120-026-00947-7","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by biallelic SMN1 variants, partially modulated by SMN2 copy number. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy in SMA. However, long-term adherence and persistence are key to sustaining benefit. We evaluated real-world adherence, persistence, and safety of risdiplam in a population-based cohort.</p><p><strong>Methods: </strong>This was a retrospective observational study including all genetically confirmed SMA type 1-3 patients treated with risdiplam in Spain between January 2020 and October 2025. Adherence was assessed using the proportion of days covered (PDC) from pharmacy dispensing records and the Morisky-Green questionnaire. Persistence was defined as time to permanent discontinuation or switch. Adverse events (AEs) were extracted from clinical records, and Kaplan-Meier analysis was used to estimate persistence probabilities.</p><p><strong>Results: </strong>Fifty-three patients were included (38 adults, 15 pediatric patients); 5.7% had SMA type 1, 52.8% type 2, and 41.5% type 3. One pediatric patient with SMA type 1 was presymptomatic at treatment initiation. Median age at risdiplam initiation was 29 years (interquartile range [IQR] 17-42), and 35.8% had prior nusinersen exposure. Adherence was high: median PDC was 100% (IQR 100-100) at 12 months and throughout follow-up; all patients assessed with the Morisky-Green questionnaire (35/53, 66%) were adherent. At 12 months, 92.5% (49/53) remained on treatment (Kaplan-Meier estimate 94.3%; 95% CI 88.3-100.0). Persistence at 24 and 36 months was 87.8% and 80.1%, respectively; later estimates should be interpreted cautiously because of the limited number of patients at risk. Median treatment duration was 28.1 months. Nine patients (17.0%) discontinued treatment. Treatment-related AEs occurred in 4/53 patients (7.5%), including one pediatric case of leukocytoclastic vasculitis requiring permanent discontinuation.</p><p><strong>Conclusions: </strong>In this real-world population-based cohort, risdiplam showed very high adherence, favorable short- to mid-term persistence, and a favorable safety profile, supporting the feasibility of oral therapy in both pediatric and adult patients with SMA.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Preferences for Subcutaneous Immunoglobulin Among Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Caregivers, and Physicians: A Discrete Choice Experiment.","authors":"Min Yang, Miriam L Zichlin, Chelsey Fix, Danni Yang, Mo Zhou, Lisa Butler, Hakan Ay, Colin Anderson-Smits","doi":"10.1007/s40120-026-00915-1","DOIUrl":"https://doi.org/10.1007/s40120-026-00915-1","url":null,"abstract":"<p><strong>Introduction: </strong>Subcutaneous immunoglobulin (SCIG) is a recommended maintenance treatment option for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and could offer greater patient convenience than intravenous immunoglobulin (IVIG). We evaluated the burden of CIDP and assessed the value that patients with CIDP, caregivers, and physicians place on various attributes of SCIG treatment options.</p><p><strong>Methods: </strong>This was an online discrete choice experiment survey designed through targeted literature review and patient/caregiver/physician interviews, conducted in Germany, the UK, and the USA. The survey was administered to adults with CIDP who were stable on IVIG and/or receiving SCIG, and caregivers/physicians. Participants chose preferred treatment profiles comprising six SCIG treatment attributes with varying levels: chance of CIDP symptom worsening, treatment frequency, number of sites per infusion, time spent on infusion per month, chance of infusion site reaction, and infusion location. Subgroup analyses were also performed. A conditional logistic regression model estimated preference weight for each attribute.</p><p><strong>Results: </strong>Overall, 146 patients, 52 caregivers, and 81 physicians completed the survey; mean (standard deviation) patient age was 58.1 (12.8) years; time since CIDP diagnosis was 8.8 (9.3) years; 98.6% had received IVIG, and 30.8% had received SCIG. Patients and caregivers experienced a substantial burden of disease that negatively impacted quality of life and work productivity. The most important factors in treatment decision-making were a lower chance of CIDP symptom worsening in 6 months, less frequent treatment administration, and home infusion (all p < 0.001 vs reference categories). Patients considered a lower chance (10% vs 20%) of symptom worsening and lower treatment frequency (every 3-4 weeks vs weekly) as the most important SCIG attributes, accounting for 64.6% of the decision weight.</p><p><strong>Conclusion: </strong>There remains a substantial burden on patients and caregivers due to CIDP. Patients with CIDP highly valued efficacy and convenience when considering preferred SCIG options. Preference awareness may facilitate shared patient-physician decision-making.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness and Safety of Ofatumumab: Analysis of B Cell Depletion, Comorbidities and Ethnicity in a Spanish Cohort.","authors":"Luis Moreno-Navarro, Lourdes Ruiz-Escribano-Menchen, Josefa Polache-Vengud, Ester Lobato-Martinez, Angel P Sempere","doi":"10.1007/s40120-026-00945-9","DOIUrl":"https://doi.org/10.1007/s40120-026-00945-9","url":null,"abstract":"<p><strong>Introduction: </strong>Ofatumumab, an anti-CD20 monoclonal antibody, is a high-efficacy disease-modifying therapy for relapsing multiple sclerosis (RMS). Although pivotal trials demonstrated substantial benefits, real-world data are required to confirm treatment persistence, effectiveness, safety, and biological markers of response in routine clinical settings. This study evaluated the real-world outcomes of ofatumumab in patients treated at a specialised multiple sclerosis (MS) centre in southeastern Spain, including exploratory analyses of B cell kinetics, comorbidity burden using the Charlson Comorbidity Index (CCI), and ethnicity.</p><p><strong>Methods: </strong>A retrospective observational study was conducted in adults with MS initiating ofatumumab between December 2022 and December 2025, with ≥ 6 months of continuous therapy. Demographic, clinical, radiological, laboratory, and pharmacological data were extracted from electronic medical records. Statistical analyses encompassed Kaplan-Meier estimates.</p><p><strong>Results: </strong>Eighty-seven patients were included (mean age 43 years; 75.9% female; 88.5% relapsing-remitting phenotype). Over a median 22-month follow-up, treatment persistence was 95.4%. Annualised relapse rate (ARR) declined from 0.48 pre-treatment to 0.03 on treatment. No evidence of disease activity (NEDA-3) was achieved in 93.1%, with no significant differences between treatment-naïve and previously treated patients. Sustained CD19⁺ B cell depletion was confirmed in all assessments. Immunoglobulin levels remained mostly stable. Ofatumumab was generally well tolerated: systemic injection-related reactions occurred in 29.9% and infections in 6.9%. Exploratory analyses showed no significant differences in relapse or magnetic resonance imaging outcomes by CCI category or ethnicity.</p><p><strong>Conclusion: </strong>In this Spanish real-world single-centre cohort, ofatumumab demonstrated high persistence, substantial suppression of inflammatory activity, and a favourable safety profile in routine clinical practice. Sustained B cell depletion aligned with clinical and radiological stability. These findings support the real-world effectiveness of ofatumumab across diverse patient profiles and complement evidence from pivotal trials. Further prospective studies with broader populations and longer follow-up are warranted to refine understanding of long-term outcomes and determinants of treatment response variability.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Factors for Non-response to First Use of Polyvalent Intravenous Immunoglobulin in Generalised Myasthenia Gravis.","authors":"Matthias Dion, Antoine Gavoille, Valérie Chamouard, Antoine Pegat, Françoise Bouhour","doi":"10.1007/s40120-026-00941-z","DOIUrl":"https://doi.org/10.1007/s40120-026-00941-z","url":null,"abstract":"<p><strong>Introduction: </strong>Myasthenia gravis (MG) is an autoimmune neurological disorder affecting the neuromuscular junction. Rapid clinical deterioration during a myasthenic crisis (MC) or severe exacerbation may be life-threatening due to respiratory or bulbar involvement. Plasma exchange (PLEX) and intravenous immunoglobulin (IVIg) are two rescue therapies that show comparable efficacy in this setting. However, the characteristics of patients who respond poorly to IVIg remain insufficiently described. The aim of this study was to identify predictive factors of non-response to IVIg administered during a first MC or exacerbation.</p><p><strong>Methods: </strong>This was a single-centre retrospective cohort study carried out at a French referral centre for neuromuscular diseases between 2017 and 2023. Adult patients with generalised MG experiencing a first MC or exacerbation and treated for the first time with IVIg were included in the study. Data on clinical, laboratory, electrophysiological and therapeutic variables were collected. Treatment response was defined as the maximum gain in Garches clinical score following IVIg, adjusted for baseline score.</p><p><strong>Results: </strong>A total of 93 were included in the study. The median age of the cohort was 68 (interquartile range [IQR] 49-76) years, and the median delay from diagnosis was 0.7 years. The median baseline Garches score was 66/100 (IQR 55-75) points, which improved to 85/100 (IQR 75-94) points after treatment. Bulbar involvement was significantly associated with a greater response to IVIg.</p><p><strong>Conclusions: </strong>In this large and heterogeneous cohort, IVIg demonstrated consistent efficacy without identification of significant predictors of non-response. These findings support IVIg as a reliable and evidence-based first-line therapy for patients with MG experiencing exacerbation or MC.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Unmet Needs of People with MS at Diagnosis and Throughout Their Care Journey: Insights from a Survey-Based Study.","authors":"Klaus Schmierer, Pieter van Galen, Helen Gray, Alice Laroni, Amanda Montague, Stanca Potra, Heidi Thompson","doi":"10.1007/s40120-026-00942-y","DOIUrl":"https://doi.org/10.1007/s40120-026-00942-y","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) has a broad range of symptoms and heterogenous trajectory that requires individualised care. To optimise shared decision-making between healthcare professionals (HCPs) and people with MS (PwMS), it is important to understand communication needs from the patient perspective at diagnosis and throughout their care journey.</p><p><strong>Methods: </strong>Two multinational online surveys were conducted to explore (1) communication needs around the time of diagnosis, and (2) PwMS empowerment in communicating their specific needs and symptoms. Questionnaires included ten close-ended questions and were shared among 100 PwMS aged 18-50 years in Australia, Spain, the UK and the USA. Anonymised data were analysed by a core panel of HCPs, PwMS and patient advocacy group representatives, and key recommendations were agreed.</p><p><strong>Results: </strong>The majority of respondents were female (65-80%) and from the UK (80-87%). PwMS and caregivers are often overwhelmed and feel 'lost' at the time of diagnosis. Early regular contact is critical for effective delivery of key information and building a trusting relationship. PwMS value a clear explanation of the healthcare team and next steps, but only around a quarter (26%) had HCP roles clearly explained. PwMS are often uncertain if health changes are related to MS and 42% reported not feeling comfortable discussing 'invisible' symptoms such as cognitive, mood and emotional changes. Most respondents (54%) reported that their MS nurse was the person they were most likely to consult. Support services were not routinely offered; only 26% were informed about patient support groups. The most reported benefit of an MS-specific patient group was 'feeling less alone'.</p><p><strong>Conclusion: </strong>Regular HCP contact after diagnosis, peer group support for PwMS and their caregivers, signposting of reliable and accurate online resources and the timely offer of support services, including psychological support, should be routine elements of care from the point of diagnosis.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Low-Sodium Oxybate in Participants with Narcolepsy: Primary Results from the DUET Study.","authors":"Logan D Schneider, Chad M Ruoff, David T Plante, Deborah A Nichols, Teresa L Steininger, Douglas S Fuller, M Todd Kirby, Sarah Akerman, Jessica K Alexander, Marisa Whalen, Alyssa Cairns","doi":"10.1007/s40120-026-00921-3","DOIUrl":"https://doi.org/10.1007/s40120-026-00921-3","url":null,"abstract":"<p><strong>Introduction: </strong>A phase 4, prospective, open-label study of low-sodium oxybate (LXB) in narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia included novel symptom outcomes important to patients (Jazz DUET; NCT05875974; registered 16 May 2023). Primary results from the narcolepsy cohort, including LXB effectiveness (nighttime sleep/daytime symptoms/overall disease severity) and safety are reported here.</p><p><strong>Methods: </strong>DUET included screening, 8-day baseline (BL; off-LXB), 2-8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT; on-LXB), and safety follow-up periods. At BL and EOT, participants underwent nocturnal polysomnography (PSG) and completed Epworth Sleepiness Scale (ESS; primary endpoint), Narcolepsy Severity Scale (NSS [NT1]; NSS-2 [NT2]), and Patient Global Impression of Severity (PGI-S) and Change (PGI-C); eDiaries for sleep quality and cataplexy (NT1 only) were completed daily for 8 days before PSGs. Least-squares mean (LSM) changes were adjusted for BL values.</p><p><strong>Results: </strong>Thirty-four participants completed the study and were analyzed (NT1, n = 16; NT2, n = 18); LSM (SE) change in ESS score (BL to EOT), - 7.7 (0.9), P < 0.0001. At EOT versus BL, transitions to lighter stages of sleep decreased (LSM [SE] - 13.1 [2.9], P < 0.0001), N3 duration increased (45.0 [8.8] min, P < 0.0001), and nocturnal awakenings decreased (- 3.2 [0.9], P = 0.0013). LSM [SE] changes in NSS and NSS-2 scores were - 19.7 (2.7) and - 11.3 (1.6). Most participants reported improved sleep quality and overall narcolepsy disease and fewer cataplexy attacks. Treatment-emergent adverse events were consistent with the known LXB safety profile.</p><p><strong>Conclusion: </strong>DUET study results demonstrated novel nighttime sleep/daytime symptom improvements in participants with narcolepsy treated with open-label LXB.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05875974.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multimodal Latent Severity Axis for Alzheimer's Disease: Probabilistic PCA, Bayesian Trajectories, and Stage-Aware Timing Effects.","authors":"Babak Haji, Amir Abbas Tahami Monfared","doi":"10.1007/s40120-026-00940-0","DOIUrl":"https://doi.org/10.1007/s40120-026-00940-0","url":null,"abstract":"<p><strong>Introduction: </strong>Multimodal Alzheimer's disease (AD) cohorts capture cognition, function, neuroimaging, and fluid biomarkers, yet overall disease severity remains difficult to summarize on a single clinically meaningful scale. The apolipoprotein E ε4 (APOE ε4) allele is the strongest common genetic risk factor for late-onset AD, but its association with \"progression\" has been inconsistent because earlier placement along the disease continuum is often conflated with faster within-stage decline.</p><p><strong>Methods: </strong>Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we analyzed an amyloid-positive baseline cohort (N = 1058) and a longitudinal subset (N = 932; ≥ 2 visits and ≥ 4 of 13 measures per visit). Measures included standardized cognitive and functional assessments, structural and functional neuroimaging, cerebrospinal fluid biomarkers of amyloid‑beta and tau pathology, and plasma neurofilament light protein as a marker of neuroaxonal injury. Magnetic resonance imaging (MRI) volumes were adjusted using amyloid-negative cognitively normal controls with quadratic age and intracranial volume terms. Probabilistic principal component analysis (PPCA) was used to derive a latent severity coordinate, defined as the first principal component (PC1). Hierarchical Bayesian random-intercept and random-slope models were used to estimate individual trajectories, partition APOE ε4 effects into baseline severity and within-stage rate, and generate genotype-stratified ages at prespecified severity landmarks. Axis stability was assessed with 100 bootstrap refits, and predictive performance was assessed with participant-level fivefold cross-validation.</p><p><strong>Results: </strong>The PC1 explained 38.7% of baseline variance and produced a clinically interpretable multimodal severity axis. Stability was high across bootstrap refits, and residual association with age was minimal after MRI volume adjustment. Higher APOE ε4 dose was associated with greater baseline latent severity, whereas within-stage rate differences were smaller than the baseline severity-position effect. A latent symptomatic landmark was reached approximately 3.0-3.3 years earlier per ε4 allele. Adding APOE improved out-of-sample prediction by about 10% without loss of calibration.</p><p><strong>Conclusions: </strong>Probabilistic principal component analysis provides a stable, multimodal, biologically informed severity axis for longitudinal modeling in amyloid-positive ADNI. Within this framework, APOE ε4 was associated primarily with latent severity position and model-implied timing along the continuum, whereas within-stage rate differences were smaller. These findings support stage-aware longitudinal inference and methodological applications within this cohort, while external clinical calibration and validation remain necessary.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Collaborative Approach to Creating Knowledge-Building Resources for the Early-Stage Parkinson's Disease Community.","authors":"Soania Mathur, Harold de Wit, Becky Jones, Evelyn Stevens, Angels Costa, Alexander Klein, Kate Trenam","doi":"10.1007/s40120-026-00935-x","DOIUrl":"https://doi.org/10.1007/s40120-026-00935-x","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease is a progressive neurodegenerative condition; there are no treatments currently available to slow disease progression, and no cure. Scientists are studying new treatments, such as disease-modifying therapies (DMTs), that may help slow progression of Parkinson's. Here, we discuss our approach to initiating a collaboration between industry and the Parkinson's community that explores the needs of people with early-stage Parkinson's and their care partners. The aim was to examine ways to build knowledge for newly diagnosed patients, align on the potential of DMTs and support discussions around any future clinical trial participation.</p><p><strong>Methods: </strong>An exploratory workshop with patient advisors, patient advocacy groups (PAGs), and industry representatives was conducted to evaluate perceptions and identify challenges related to understanding disease modification in early-stage Parkinson's, including the development of a preliminary DMT narrative. Patients and care partners also completed a DMT perceptions questionnaire and tested the narrative for readability. A Strategic Patient Council (SPC) then guided refinement of the narrative and co-created a knowledge-building guide for the Parkinson's community.</p><p><strong>Results: </strong>A total of 181 people with Parkinson's and their care partners completed the questionnaire. Of these, 72% strongly agreed on the need for new Parkinson's treatments, yet 59% felt that they lacked sufficient knowledge around symptom progression. Based on these data and feedback from the SPC, which comprised nine people from five PAGs, the DMT narrative was revised, leading to improved health literacy from 40% to 61%, within the 'adequate' range of the Suitability Assessment of Materials tool. The knowledge-building guide, informed by SPC input, incorporated a patient-centric framework and described key elements of living with early-stage Parkinson's, ranging from coping with diagnosis to clinical trial involvement.</p><p><strong>Conclusion: </strong>A collaboration between industry and the Parkinson's community enabled successful development of knowledge-building materials tailored for people living with early-stage Parkinson's, empowering them with a clearer understanding of emerging innovative therapies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Characteristics and Healthcare Resource Utilization Among Patients with Myasthenia Gravis Initiating Rozanolixizumab: A US Claims Database Analysis.","authors":"Mohita Kumar, Alexandria Harrold, Minjee Park, Aaksa Nair, Kristina Bardenheuer, Thaïs Tarancón, Angela Ting, Diogo Pata","doi":"10.1007/s40120-026-00939-7","DOIUrl":"https://doi.org/10.1007/s40120-026-00939-7","url":null,"abstract":"<p><strong>Introduction: </strong>Rozanolixizumab is indicated for the treatment of adults with generalized myasthenia gravis (MG). This retrospective, non-interventional cohort study evaluated adults with MG initiating rozanolixizumab in the USA.</p><p><strong>Methods: </strong>Patients were selected from de-identified claims data from the Komodo Healthcare Map^® (July 2023-March 2025). Enrolled patients were aged ≥ 18 years with MG diagnosis, ≥ 1 rozanolixizumab medical/pharmacy claim, and continuous enrollment/plan coverage for 12 months (baseline period) before first rozanolixizumab treatment initiation (index date). The follow-up period was from 1 day post-index to last enrollment date. Treatment patterns and healthcare resource utilization (HCRU) were assessed during baseline and follow-up. A second study (July 2023-June 2024) assessed patients for 12 months post-index who had ≥ 1 efgartigimod claim ≤ 12 months prior to index.</p><p><strong>Results: </strong>The main study included 719 patients. Patients with ≥ 365 days since rozanolixizumab initiation (n = 287) started a mean (standard deviation) 2.9 (1.8) treatment cycles in Year 1. Total MG-related HCRU incidence rates per 100 person-years were 88.0 during baseline and 82.9 during follow-up, and 86.2 versus 80.8 for outpatient, 25.6 versus 17.3 for inpatient, and 24.9 versus 14.0 for emergency room visits. Approximately half (53.7%, 386/719) of patients used corticosteroids at baseline and had ≥ 3 months' follow-up. 29.0% (n = 112) tapered their dose by ≥ 5 mg, and a further 29.3% (n = 113) discontinued corticosteroids during follow-up. In patients who had ≥ 1 claim for efgartigimod before initiating rozanolixizumab (n = 26), 19.2% tapered corticosteroids by ≥ 5 mg during follow-up, and 7.7% discontinued completely.</p><p><strong>Conclusion: </strong>This real-world study of patients receiving rozanolixizumab in the USA showed reductions in corticosteroid use and HCRU following rozanolixizumab initiation, including in those who switched from efgartigimod. The mean number of rozanolixizumab cycles (2.9) was lower than the mean 4.1 cycles in Phase 3 studies (patients with ≥ 1 year of follow-up), demonstrating that treatment patterns in clinical practice can be individually adjusted.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}