Neurology and Therapy最新文献

{"title":"Comparative Efficacy of Double-Filtration Plasmapheresis Versus Intravenous Methylprednisolone in Acute Attacks of Neuromyelitis Optica Spectrum Disorder: A Prospective Cohort Study.","authors":"Xiwen Ai, Qiuju Li, Kan Wang, Jing Peng, Desheng Zhu, Yangtai Guan","doi":"10.1007/s40120-025-00835-6","DOIUrl":"https://doi.org/10.1007/s40120-025-00835-6","url":null,"abstract":"<p><strong>Introduction: </strong>While double-filtration plasmapheresis (DFPP) and intravenously administered methylprednisolone (IVMP) are both established treatments for acute attacks of neuromyelitis optica spectrum disorder (NMOSD), their comparative efficacy and safety profiles remain a critical area of investigation. This study aimed to evaluate the clinical outcomes and adverse events of DFPP versus IVMP in patients with NMOSD, with a focus on disability improvement and treatment tolerability.</p><p><strong>Methods: </strong>A prospective single-center cohort study was performed with 146 patients with NMOSD, who were treated with DFPP, IVMP, and combination therapy (DFPP + IVMP). Primary efficacy was measured by changes in Expanded Disability Status Scale (EDSS) scores (ΔEDSS). Secondary outcomes included Modified Rankin Scale (mRS) scores. Safety profiles, including liver enzyme elevation and infection rates, were monitored.</p><p><strong>Results: </strong>The DFPP group (n = 81) demonstrated a significant clinical response, with a median EDSS improvement of 0.5 (IQR 0.0-1.0) points. The response rate (defined as ΔEDSS > 0) was 66.7%, with 33.3% (27/81), 18.5% (15/81), and 14.8% (12/81) of patients achieving improvements of 0.5, 1.0, and ≥ 1.5 points, respectively. This was accompanied by a marked reduction in serum immunoglobulins (IgG: 11.87 ± 4.39 to 3.13 ± 1.76 g/L, p < 0.001). The DFPP group and IVMP monotherapy group showed comparable efficacy, with 66.7% (54/81) and 69.2% (45/65) of patients achieving EDSS improvement, respectively (OR 0.89, 95% CI 0.45-1.77, p = 0.742). The magnitude of EDSS improvement was identical between groups (median ΔEDSS 0.5 points). Combination therapy demonstrated particular utility in severe cases (median baseline EDSS 5.0 [IQR 3.5-6.5]). Adverse events were fewer with DFPP than with IVMP (19.8% vs. 33.8%, p = 0.059).</p><p><strong>Conclusion: </strong>DFPP exhibited comparable effectiveness to IVMP in improving disability during NMOSD acute attacks, with a trend towards a more favorable safety profile. The combination of DFPP and IVMP may benefit severe cases. These findings support DFPP as a viable therapeutic option, particularly for patients with high baseline disability or steroid-refractory disease.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232954","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":"Improvement in Motor Consistency and Stability with Foslevodopa/Foscarbidopa in Advanced Parkinson's Disease: Post Hoc Analysis of Two Phase 3 Clinical Trials.","authors":"Rajesh Pahwa, Jason Aldred, Michael J Soileau, David G Standaert, Victor S C Fung, Thomas Kimber, Irene A Malaty, Diego Santos-García, Camille Carroll, Tove Henriksen, Ashwini Parab, Connie H Yan, Maurizio F Facheris, Amy Spiegel, Linda Harmer, Jorge Zamudio, K Ray Chaudhuri","doi":"10.1007/s40120-025-00827-6","DOIUrl":"https://doi.org/10.1007/s40120-025-00827-6","url":null,"abstract":"<p><strong>Introduction: </strong>People with advanced Parkinson's disease (aPD) frequently experience unpredictable \"Off\" time and debilitating motor fluctuations. Foslevodopa/foscarbidopa (LDp/CDp), a levodopa/carbidopa (LD/CD) prodrug, is delivered as a 24-h continuous subcutaneous infusion. This post hoc analysis evaluated the efficacy of LDp/CDp in achieving consistent motor symptom control and stable motor states in people with aPD.</p><p><strong>Methods: </strong>Diaries of people with aPD treated with LDp/CDp participating in a 12-week, phase 3, randomized controlled trial (RCT) were evaluated versus oral LD/CD, and in a 52-week open-label, single-arm trial (OLT) with LDp/CDp alone. Motor symptom control was assessed by frequency (30-min intervals) and duration (4-h blocks) of motor states (good \"On\" time [without dyskinesia or troublesome dyskinesia] or \"Off\" time) over a 16-h waking day. Motor state stability was evaluated by changes in daily motor fluctuations and extreme fluctuations (defined as transition from \"Off\" to \"On\" with troublesome dyskinesia, or vice versa). Outcomes were analyzed using adjusted regression models.</p><p><strong>Results: </strong>Analysis included 47 (RCT) and 55 (OLT) people with aPD on LDp/CDp. In the RCT, LDp/CDp had an approximately 1-h gain in good \"On\" time in the mornings versus a quarter-hour gain for those on LD/CD (P = 0.001), with > 80% of participants on LDp/CDp waking up in good \"On.\" At week 12, fewer motor fluctuations/day occurred with LDp/CDp versus LD/CD (3.2 vs 5.3; nominal P = 0.001), and twice as many participants on LDp/CDp had ≤ 3 fluctuations/day (53.2% vs 25.8%). In the OLT, the results seen at 12 weeks were sustained through week 52, with fewer mean fluctuations/day (3.1) than baseline (7.4) and more participants reporting ≤ 3 fluctuations/day at 52 weeks (66.6%) versus baseline (12.9%).</p><p><strong>Conclusion: </strong>LDp/CDp provided consistent motor symptom control throughout the day, enhanced motor state stability, and reduced motor fluctuation, highlighting LDp/CDp's potential to significantly improve the management of unpredictable motor states and overall quality of life for people with aPD.</p><p><strong>Trial information: </strong>Clinicaltrials.gov ID: NCT04380142, NCT03781167.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225815","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":"Expert Guidance on Cognitive Impairment in Alzheimer's Disease: A Practical Seven-Step Approach from the United Arab Emirates.","authors":"Tauofik Alsaadi, Abubaker Almadani, Suhail AlRukn, Ali Hassan, Pournamy Sarathchandran, Ahmed Shatila, Miklos Szolics, David Benito, Soydan Ince, Derk W Krieger","doi":"10.1007/s40120-025-00833-8","DOIUrl":"https://doi.org/10.1007/s40120-025-00833-8","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive impairment (CI) spans a spectrum from mild CI to severe dementia, with Alzheimer's disease (AD) the most prevalent cause of CI and dementia. Although dementia burden and prevalence in Arab countries reflect general global trends, the United Arab Emirates (UAE) differs from Western countries both culturally and regarding management resources. Further guidance is therefore needed for the diagnosis and management of CI in the UAE.</p><p><strong>Methods: </strong>A task force of eight neurologists and two non-voting collaborators with special dementia expertise was convened to develop evidence-based position statements/recommendations to guide the diagnosis and management of AD, including the use of amyloid-targeting therapies (ATTs), in the UAE clinical setting. A modified Delphi survey method was chosen to obtain a consensus, ensuring that drafted expert statements reflected diverse perspectives and experiences. Discordance was predefined as > 25% of panelists rating an expert statement as ≤ 3 on the Likert scale. Consensus was predefined as a median rating ≥ 7 without discordance. Expert statements achieving consensus were adopted.</p><p><strong>Results: </strong>A seven-step framework for diagnosing and managing CI in the UAE was developed, with consensus achieved on all statements. Recommendations largely aligned with international guidelines on AD dementia management and treatment, combined with UAE-specific guidance. The framework spans the full patient journey from initial symptoms to diagnosis (including biomarker use), initial treatment (including ATTs where appropriate), and subsequent monitoring and management as the disease progresses.</p><p><strong>Conclusions: </strong>Management of CI and dementia in UAE requires consideration of international guidelines in the context of regional and local cultural sensitivities and healthcare resources. A holistic approach is recommended, combining appropriate pharmacological treatment with lifestyle interventions, education, and support for patients and care partners. Patients require ongoing monitoring to ensure the approach is tailored to the disease stage and provides optimal quality of life and reduced burden for patients and care partners.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225788","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":"Associations of Folate and Homocysteine Levels with Futile Recanalization in Acute Ischemic Stroke After Successful Endovascular Thrombectomy.","authors":"Taoyuan Lu, Wenbo Cao, Bin Yang, Dechao Wang, Jinzi Wei, Liqun Jiao, Xin Xu","doi":"10.1007/s40120-025-00837-4","DOIUrl":"https://doi.org/10.1007/s40120-025-00837-4","url":null,"abstract":"<p><strong>Introduction: </strong>Our preliminary study identified two metabolically distinct thrombus subtypes, demonstrating enhanced lipid metabolic signatures but downregulated folate biosynthesis pathways associated with poor prognosis. This study aimed to assess the prognostic value of routine laboratory parameters involved in lipid and folate metabolism for predicting 90-day futile recanalization (FR) in patients with anterior circulation acute ischemic stroke caused by large vessel occlusion (AIS-LVO) who achieved successful recanalization by endovascular thrombectomy.</p><p><strong>Methods: </strong>Consecutive patients with anterior circulation AIS-LVO who achieved successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3) were retrospectively screened from April 2019 to February 2024. Admission serum levels of traditional and non-traditional lipid parameters, folate, and homocysteine (Hcy) were measured. FR was defined as a 90-day modified Rankin Scale score of 3-6, despite successful recanalization. Multivariable logistic regression was performed to identify predictors for FR, which were incorporated into a predictive nomogram.</p><p><strong>Results: </strong>Among 446 enrolled patients [median age 65 (IQR, 56-72.75) years; 32.1% female], 210 (47.1%) experienced 90-day FR. Multivariate logistic regression analysis revealed that lower admission serum folate and higher Hcy levels were independently associated with increased 90-day FR risk. In contrast, neither admission traditional or non-traditional lipid parameters were independent predictors. The addition of folate and Hcy, individually or combined, significantly improved the predictive performance of conventional clinical factor-based model, as reflected by significant increases in net reclassification improvement and integrated discrimination improvement. Finally, a predictive nomogram was developed incorporating age, admission National Institute of Health Stroke Scale, puncture-to-recanalization time, and admission serum glucose, folate, and Hcy levels.</p><p><strong>Conclusions: </strong>Admission serum folate and Hcy levels are independent predictors of 90-day FR risk and may enhance risk stratification and guide personalized secondary prevention strategies in patients with successfully recanalized AIS-LVO.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213172","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":"Safety and Effectiveness of Direct Oral Anticoagulants in Combination with Antiseizure Medications: Protocol for a Systematic Review and Meta-analysis.","authors":"Kai Michael Schubert, Johan Zelano, David J Seiffge, Francesco Brigo, Eugen Trinka, Nishant K Mishra, Emilio Russo, Marian Galovic","doi":"10.1007/s40120-025-00836-5","DOIUrl":"https://doi.org/10.1007/s40120-025-00836-5","url":null,"abstract":"<p><strong>Introduction: </strong>The concurrent use of direct oral anticoagulants (DOACs) and antiseizure medications (ASMs) is increasingly common, particularly among patients with atrial fibrillation, stroke, and epilepsy. Certain ASMs may affect the pharmacokinetics of DOACs through enzyme induction or modulation of P-glycoprotein, potentially altering their effectiveness and safety. However, evidence regarding these interactions and their impact on clinical outcomes remains limited, heterogeneous, and inconsistently reported. The objective of this systematic review is to synthesize current evidence on cerebrovascular outcomes, bleeding risk, and pharmacokinetic effects in patients treated concurrently with DOACs and ASMs.</p><p><strong>Methods: </strong>This protocol outlines a systematic review and meta-analysis of randomized controlled trials, observational studies, case-control studies, and pharmacokinetic investigations involving patients aged 8 years or older treated with DOACs in combination with ASMs. Databases including MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) will be searched without language restrictions. Additional studies will be identified via reference screening, expert contact, and AI-assisted evidence discovery (Elicit). Dual independent review will be applied for study selection, data extraction, and risk of bias assessment using validated tools (Newcastle-Ottawa Scale (NOS), the Quality In Prognosis Studies (QUIPS) tool, and the Cochrane Risk of Bias 2.0 tool). Where appropriate, meta-analysis will be performed using random-effects models; otherwise, results will be synthesized narratively in accordance with SWiM (Synthesis Without Meta-analysis) guidelines.</p><p><strong>Planned outcomes: </strong>Primary effectiveness outcome: composite of ischemic stroke and systemic embolism (IS/SE).</p><p><strong>Secondary outcomes: </strong>ischemic stroke alone, systemic embolism alone, transient ischemic attack (TIA), major bleeding, intracranial hemorrhage, pharmacokinetic measures, and seizure occurrence. Subgroup analyses will stratify by ASM type, pharmacokinetic interaction potential, age groups (8-17, ≥ 18 years), and DOAC indications (e.g., non-valvular atrial fibrillation, venous thromboembolism, left ventricular thrombus). An individual participant data (IPD) meta-analysis is planned if sufficient eligible data are available. A summary table of outcomes and definitions (Table 1) and an overview flow diagram of the planned process (Fig. 1) are provided.</p><p><strong>Systematic review registration: </strong>PROSPERO CRD4201050986.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213195","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":"Antiseizure Medications and Bone Health.","authors":"Paula V Gaete, Valentina Cuellar-Rodríguez, Carlos O Mendivil","doi":"10.1007/s40120-025-00805-y","DOIUrl":"10.1007/s40120-025-00805-y","url":null,"abstract":"<p><p>Epilepsy frequently requires treatment with antiseizure medications (ASM). With the progressive rise in life expectancy in this population, patients are more exposed to potential undesirable effects, some of them on bone tissue. Here, we review current knowledge concerning the impact of ASM on bone biology. Cytochrome P450 inductors decrease serum concentrations of active vitamin D, increasing parathyroid hormone (PTH) secretion and hence bone resorption. Valproic acid also reduces active vitamin D, but in addition activates osteoclasts and impairs osteoblastic function through different pathways. Although the mechanism remains unclear, topiramate is associated with reductions in bone mineral density and increased PTH. Levetiracetam has a very favorable bone profile. Lacosamide and lamotrigine have a preferable bone effect compared to other sodium channel blockers. These ASM with a lower impact on bone biology should be prioritized whenever possible. Every person with epilepsy receiving high-risk ASM should undergo fracture risk assessment.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1827-1844"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Intervention and Speed-to-Effect in Spinal Muscular Atrophy Type 1 Following Onasemnogene Abeparvovec Gene Replacement Therapy: Results of aPost-Hoc Analysis of Pooled Clinical Study Data.","authors":"Walter Toro, Sandra P Reyna, Shannon Ritter, Anish Patel, Nayla Mumneh, Omar Dabbous","doi":"10.1007/s40120-025-00791-1","DOIUrl":"10.1007/s40120-025-00791-1","url":null,"abstract":"<p><strong>Introduction: </strong>Studies suggest that early intervention with disease-modifying treatment for spinal muscular atrophy (SMA) might provide the best opportunity for optimal outcomes. One such treatment is onasemnogene abeparvovec, a gene replacement therapy with durable efficacy demonstrated in clinical trials, long-term studies, and real-world data (e.g., RESTORE registry).</p><p><strong>Methods: </strong>A pooled post-hoc analysis was conducted to assess the early post-treatment impact of intravenous onasemnogene abeparvovec on motor function and event-free survival for symptomatic infants with SMA type 1 (i.e., non-sitters). Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores and event-free survival were evaluated for patients enrolled in the START, STR1VE-US, and STR1VE-EU clinical trials.</p><p><strong>Results: </strong>The pooled analysis set included 67 patients. Mean (SD) CHOP INTEND score at baseline was 29.3 (9.58) points. Rapid increases in mean CHOP INTEND of 7.0, 9.7, and 11.8 points were observed at 1, 2, and 3 months post-dose, respectively. At 6 months post-dose, 54/59 infants (91.5%) treated with onasemnogene abeparvovec achieved a clinically significant ≥ 4-point improvement in CHOP INTEND score from baseline, with a mean (SD) CHOP INTEND score of 44.3 (9.92) points. Patients who received onasemnogene abeparvovec had longer ventilation-free survival compared with natural history, with a statistically significant separation from the natural history cohort being maintained throughout follow-up.</p><p><strong>Conclusions: </strong>Rapid and clinically significant improvements in motor function were observed for onasemnogene abeparvovec-treated patients with symptomatic SMA type 1. Early diagnosis and treatment are essential for timely restoration and preservation of motor neurons and maximal motor function improvement.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1903-1918"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-Year Safety and Efficacy Outcomes with Ofatumumab in Patients with Relapsing Multiple Sclerosis.","authors":"Stephen L Hauser, Jeffrey A Cohen, Jérôme de Sèze, Sven G Meuth, Paul S Giacomini, Jin Nakahara, Celia Oreja-Guevara, Derrick Robertson, Sibyl Wray, Alit Bhatt, Xixi Hu, Jing Xi, Rebecca Piccolo, Valentine Jehl, Roseanne Sullivan, Ibolya Boer, Heinz Wiendl, Ludwig Kappos","doi":"10.1007/s40120-025-00784-0","DOIUrl":"10.1007/s40120-025-00784-0","url":null,"abstract":"<p><strong>Introduction: </strong>Ofatumumab demonstrated superior efficacy and similar safety versus teriflunomide in ASCLEPIOS I/II in people with relapsing multiple sclerosis; no new safety concerns and sustained efficacy were observed up to 4 years in the open-label extension study ALITHIOS. Here, we further characterise the safety and efficacy of ofatumumab up to 5 years by discussing infection outcomes in the COVID-19 era and providing a comprehensive overview of participant disability outcomes.</p><p><strong>Methods: </strong>Safety (N = 1969; participants who received ≥ 1 dose of ofatumumab in ASCLEPIOS I/II, APLIOS, APOLITOS, or ALITHIOS) and efficacy sets (N = 1882; participants randomised to ofatumumab [OMB-OMB] or teriflunomide [TER-OMB] in ASCLEPIOS I/II, regardless of whether they entered ALITHIOS) were analysed. Data cutoff: 25 September 2022.</p><p><strong>Results: </strong>The exposure-adjusted incidence rates (per 100 patient-years) of adverse events (AEs, 124.65), serious AEs (4.68), serious infections (1.63), and malignancies (0.32) remained consistent with previous findings up to 5 years of follow-up, with no new safety signals identified. With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse rates (ARR) remained low, and magnetic resonance imaging (MRI) activity was almost completely suppressed with OMB-OMB through years 1-5; after switching from teriflunomide (years 2-3), pronounced reductions in ARR/MRI activity were observed with low rates sustained through years 3-5. During year 5, 9 of 10 participants in both groups were free of disease activity (NEDA-3).</p><p><strong>Conclusion: </strong>Ofatumumab has a favourable benefit-risk profile that is sustained up to 5 years.</p><p><strong>Trial registration: </strong>ALITHIOS (NCT03650114): https://clinicaltrials.gov/ct2/show/NCT03650114.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1975-1992"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Societal Costs and Efficiency of Subcutaneous versus Intravenous Lecanemab in Early Alzheimer's Disease: A U.S. Cost Comparison Model.","authors":"Amir Abbas Tahami Monfared, Stephanie Barrows, Lindsey Fox, Brittney Herbel, William L Herring, Alisha Krumbach, Quanwu Zhang","doi":"10.1007/s40120-025-00790-2","DOIUrl":"10.1007/s40120-025-00790-2","url":null,"abstract":"<p><strong>Introduction: </strong>Intravenous (IV) therapies often impose significant burdens and costs on payers, providers, patients, and caregivers. A fixed-dose subcutaneous (SC) formulation may enhance convenience, improve outcomes, and reduce societal costs compared with weight-based IV dosing. This study estimated the relative societal value and cost implications of IV versus SC lecanemab administration for early Alzheimer's disease (AD) in the USA.</p><p><strong>Methods: </strong>A targeted literature review identified outcomes related to IV and SC modes of administration across therapeutic areas to inform and parameterize a cost-comparison model. The model incorporated direct treatment costs; economic value of administration time for providers, patients, and caregivers; and quality-of-life (QOL) impacts for patients and caregivers. Costs were estimated from a societal perspective over 4 years, including a per-patient head-to-head analysis and a population-level assessment accounting for population size, current treatment rates, and SC uptake. Scenario analyses evaluated the impact of key inputs and assumptions on study findings.</p><p><strong>Results: </strong>SC lecanemab was estimated to yield per-patient savings of $72,891-$80,925 over 4 years compared with IV administration, corresponding to annual savings of $18,223-$20,231 at willingness-to-pay thresholds of $150,000 and $200,000 per quality-adjusted life-year gained, respectively. Savings stemmed from a $40,638 reduction in treatment costs, $8151 decrease in administration time costs, and $24,102-$32,136 reduction in QOL-related costs. At the population level, assuming current treatment rates and 49.4% SC uptake, total savings of $3.16-$3.71 billion were projected over 4 years. Sensitivity analyses indicated per-patient savings varied based on site of care, IV drug wastage, and caregiver disutilities, while population-level savings were sensitive to treatment rates and SC uptake.</p><p><strong>Conclusion: </strong>Subcutaneous lecanemab administration potentially offers substantial societal savings by lowering treatment costs, minimizing time demands, and relieving QOL burdens for patients and caregivers. These findings underscore the potential value of SC formulations in improving treatment delivery and alleviating AD economic impact; however, real-world data in AD are needed to further contextualize this comparison.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1863-1888"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the Present and Future Pharmacologic Treatment of Parkinson's Disease.","authors":"Thomas Müller","doi":"10.1007/s40120-025-00800-3","DOIUrl":"10.1007/s40120-025-00800-3","url":null,"abstract":"<p><p>Symptomatic drug treatment of Parkinson's disease combines various pharmacological principles for a patient-tailored drug combination. Development of more continuous delivery modes of dopamine-substituting drugs with formulations with better pharmacokinetic properties has enabled less frequent dosing and thereby provided further benefit for patients. Peripheral weakening of dopa decarboxylase activity with nutrients, such as short fatty acids, may enhance levodopa efficacy. A future concept may be mandatory combined central inhibition of catechol-O-methyltransferase, monoamine oxidase B and tyrosinase in levodopa-treated patients, if tolerated. This approach may hypothetically protect against toxins resulting from catecholamine metabolism. Beneficial modification of disease progression and cure is an unmet need. High expectations were mainly generated by promising positive experimental research outcomes. The employed models of Parkinson's disease provide uniform trial conditions. Drug safety and the side effect profile have minor importance. Subsequently performed translational clinical trials failed. Examples are studies with iron chelators, glucagon-like peptide 1 receptor agonists and free radical scavengers, particularly when levodopa-naïve patients were included. Multifactorial heterogeneity of disease mechanisms, variability of symptoms and their progression are the main causes for these negative results. Additionally an impact of symptomatic dopamine-substituting treatments on the course of Parkinson's disease was demonstrated in clinical studies with monoamine oxidase B inhibitors and dopamine agonists with levodopa therapy as comparator. Neuron transplantation, application of stem cells and their secreted exosomes, or secretomes, are still mainly considered by experimental researchers. Translation into clinical practice is complex or has failed. Stimulation of an existing endogenous repair system in the peripheral and central nervous system is an alternative. Repulsive guidance molecule A (RGMa) inhibits physiologic regeneration in peripheral and central neurons. Blocking of the physiologic effects of this protein initiates endogenous repair in models of acute and chronic neuronal dying as a more general therapeutic concept for chronic neurodegenerative and inflammatory disease.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1769-1781"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}