Neurology and Therapy最新文献

{"title":"Migraine and Obesity: From Shared Mechanisms to Therapeutic Strategies.","authors":"Marta Waliszewska-Prosół, Bianca Raffaelli, Lanfranco Pellesi, Alberto Raggi, Dilara Onan, Karol Marschollek, Danilo Antonio Montisano, Claudio Tana, Paolo Martelletti","doi":"10.1007/s40120-026-01050-7","DOIUrl":"https://doi.org/10.1007/s40120-026-01050-7","url":null,"abstract":"<p><p>Migraine and obesity are highly prevalent, chronic conditions that frequently coexist, presenting a significant clinical and therapeutic challenge. Their relationship is multifactorial and bidirectional, albeit with more consistent evidence supporting obesity as a contributor to migraine than the converse, driven by shared biological mechanisms that include systemic low-grade inflammation, adipose-derived adipokines, metabolic dysfunction, and insulin resistance. These systemic disturbances converge on hypothalamic dysregulation and altered neuropeptide signaling, notably involving calcitonin gene-related peptide (CGRP), ultimately promoting trigeminovascular activation and migraine chronification. Clinically, excess body weight is associated with increased attack frequency, greater pain intensity, and higher disability, particularly in women of reproductive age. Conversely, migraine can indirectly influence factors contributing to weight gain, often compounded by psychological comorbidities. Management requires an integrated approach; traditional oral preventives that promote weight gain should be avoided, prioritizing sustainable lifestyle interventions alongside modern, weight-neutral or weight-reducing therapies. This article reviews the available evidence documenting the complex pathophysiological link between obesity and migraine, diagnostic and clinical implications across specific populations, and current management strategies. Emphasis is placed on novel therapeutic options, including CGRP-targeted agents and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as future directions and unmet clinical needs in the management of comorbid migraine and obesity.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148097","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":"Insights from a Multi-Country Survey: Healthcare Providers' Perspectives on the Management of Adults with Neurofibromatosis Type 1 and Plexiform Neurofibroma.","authors":"Ayo Adeyemi, Rosalie E Ferner, Phioanh L Nghiemphu, Michelle Erdmann, Susanna Burckhardt, Abby Crites, Theresa Dettling","doi":"10.1007/s40120-026-01026-7","DOIUrl":"https://doi.org/10.1007/s40120-026-01026-7","url":null,"abstract":"<p><strong>Introduction: </strong>Neurofibromatosis type 1 (NF1) is a genetic, multi-system disorder characterized by a range of manifestations. Approximately 50% of patients with NF1 develop peripheral nerve sheath tumors [plexiform neurofibroma (PN)], which can cause substantial morbidity and often progress into adulthood. Historically, NF1-PN research has focused on pediatric patients; however, less is known in adult patients, in whom treatment options are also limited. This study aimed to provide insights into the management and treatment challenges in adults with NF1-PN from the perspective of healthcare providers (HCPs).</p><p><strong>Methods: </strong>Two separate studies, one in the US and one across multiple countries (Canada, China, France, Germany, Japan, Italy, Spain, and the UK), were conducted with a mixed-methods, double-blinded design among HCPs who treat adults with NF1-PN. Qualitative interview data were collected to explore survey responses (US) or to inform quantitative study design (multi-country); quantitative data were collected through online surveys.</p><p><strong>Results: </strong>Overall, 4 and 16 HCPs participated in the qualitative portion of the US and multi-country studies, whereas 41 and 124 HCPs participated in the quantitative portion, respectively. Physical examinations and radiologic imaging were used for diagnosis of NF1-PN across both studies, but family history was more frequent in the multi-country study (81-83% multi-country; 68-75% US). HCPs reported managing multiple high-burden manifestations, including brainstem or optic gliomas, hearing issues, neurocognitive or visual impairment, and neuropathic pain, resulting in patients missing an average of 6-8 days from school or work per month. Approximately 17-25% of patients drop out of care when transitioning from pediatric to adult care with lack of support/processes/guidelines noted as key challenges.</p><p><strong>Conclusion: </strong>These results highlight unmet clinical needs in treatment of adults with NF1-PN worldwide; specifically, limited treatment options for PN growth and symptoms. HCPs identified need for better educational resources for patients and improved transition-of-care processes/resources.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137670","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":"Triple Preventive Therapy with OnabotulinumtoxinA, Fremanezumab, and Atogepant in Treatment-Resistant Chronic Migraine: A 52-Week Pilot Case Series (TRIPLE Cohort).","authors":"Marina Romozzi, Luigi Francesco Iannone, Antonio Russo, Ian Finkelstein, Dineo Seabi, Adam Ahlden, Anne Hege Aamodt, Catello Vollono, Paolo Calabresi, Edoardo Caronna, Patricia Pozo-Rosich, Erling Andreas Tronvik, Christina Sundal","doi":"10.1007/s40120-026-01045-4","DOIUrl":"https://doi.org/10.1007/s40120-026-01045-4","url":null,"abstract":"<p><strong>Introduction: </strong>A substantial proportion of patients with chronic migraine (CM) experience persistent disability despite advanced preventive monotherapies, including onabotulinumtoxinA (BoNT-A) and calcitonin gene-related peptide (CGRP)-targeted drugs. Evidence supporting combination strategies remains limited. We evaluated the long-term effectiveness and safety of triple preventive therapy with BoNT-A, fremanezumab, and atogepant in a real-world CM population with refractory disease.</p><p><strong>Methods: </strong>This ambispective, single-center case series included 14 adults with refractory CM treated sequentially with BoNT-A, fremanezumab, and add-on atogepant (60 mg daily). Patients were followed prospectively for 52 weeks during triple therapy. Primary outcomes were changes in monthly migraine days (MMDs) and monthly headache days (MHDs) through week 52. Secondary outcomes included acute medication use, responder rates, patient-reported outcomes, working status and descriptively reported adverse events and blood-pressure changes. The Patient Global Impression of Change (PGIC) evaluated overall patient-perceived clinical improvement.</p><p><strong>Results: </strong>During triple therapy, MHDs declined from 24.4 ± 2.9 at baseline (stable BoNT-A plus fremanezumab treatment) to 19.0 ± 9.4 at week 52 (overall p = 0.029), with post hoc significance reached only at week 52 (p = 0.020), indicating a delayed treatment effect to reach statistical significance. MMDs decreased progressively to 9.6 ± 5.3 at week 52 (p < 0.001). The ≥ 50% responder rate increased from 28.6% at week 24 to 42.9% at week 52. Acute medication days declined from 12.1 ± 2.4 at baseline to 6.9 ± 2.7 at week 52 (p < 0.001). PGIC scores were 6.5 ± 0.5 at week 52, indicating moderate-to-marked improvement. Working capacity improved substantially, with full-time activity increasing from 21.4% (3/14) at baseline to 71.4% (10/14) at week 52. No serious adverse events or treatment discontinuations were observed in this small cohort.</p><p><strong>Conclusion: </strong>In selected patients with treatment-resistant CM, triple preventive therapy was associated with delayed but clinically meaningful reductions in migraine burden and disability. No major tolerability issues were observed, although the small sample size precludes conclusions regarding safety. These findings support further evaluation of combination strategies in controlled studies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112707","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":"Predictors of Seizure Occurrence After Mild Cognitive Impairment and Alzheimer's Disease in Older Adults in the Veterans Affairs Healthcare System: A Retrospective Cohort Study.","authors":"Myriam Abdennadher, Ying Wang, Joel Reisman, Wen Hu, Peter Morin, Dan R Berlowitz, Brant Mittler, Amir Abbas Tahami Monfared, Quanwu Zhang, Weiming Xia","doi":"10.1007/s40120-026-01047-2","DOIUrl":"https://doi.org/10.1007/s40120-026-01047-2","url":null,"abstract":"<p><strong>Introduction: </strong>This was a retrospective epidemiological study to identify the predictors of incidence seizures among older adults with all-cause mild cognitive impairment (MCI) and Alzheimer's disease (AD) receiving care in the Veterans Affairs Healthcare System (VAHS).</p><p><strong>Methods: </strong>Veterans aged ≥ 50 years with MCI or AD were identified using pre-specified diagnostic code and clinical note algorithms in VAHS electronic health records, with linkage to Medicare claims where available, during 2016-2023. Seizures were identified using ICD-10-CM codes for convulsions and epilepsy (R56.x and G40.x), excluding codes considered unlikely to represent unprovoked seizures (e.g., G40.5). Individuals with any seizure/epilepsy diagnosis prior to the index MCI/AD date (or matched control date) were excluded. Multivariate Cox proportional hazards models were used to estimate associations but not causal relationships between baseline comorbidities and subsequent seizure risk.</p><p><strong>Results: </strong>A total of 747,475 individuals with AD or MCI and 747,475 age- and sex-matched non-MCI/AD comparators were identified; after excluding those with pre-index seizures, the analytic cohorts included 482,364 MCI, 223,312 AD, and 736,118 comparator veterans. Compared with non-MCI/AD controls, seizure risk was higher in MCI (HR 2.89, 95% CI 2.80-2.99) and AD (HR 3.19, 95% CI 2.99-3.41). In adjusted analyses, seizure risk was higher among black veterans (HR 1.38, 95% CI 1.31-1.46) than white veterans. Comorbidities with the strongest adjusted associations included traumatic brain injury (HR 1.88, 95% CI 1.68-2.10), central nervous system infection (HR 1.88, 95% CI 1.21-2.92), cerebrovascular disease (HR 1.72, 95% CI 1.63-1.81), and hemorrhagic stroke (HR 1.61, 95% CI 1.39-1.86). Much of the excess risk was associated with cerebrovascular and neurologic comorbidity.</p><p><strong>Conclusion: </strong>Our study showed that seizure risk is elevated in MCI and AD, with specific comorbidities associated with risk of seizure occurrence and cognitive decline, suggesting potentially actionable targets for risk stratification and clinical monitoring.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112176","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":"Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine in Adults of Hispanic or Latino Ethnicity: Post Hoc Analysis of Three Randomized, Placebo-Controlled Trials.","authors":"Julio R Vieira, Meghan Fajardo, Chandra Abbott, Jessica Li, Michael T Sellix","doi":"10.1007/s40120-026-01025-8","DOIUrl":"https://doi.org/10.1007/s40120-026-01025-8","url":null,"abstract":"<p><strong>Introduction: </strong>This post hoc exploratory analysis evaluated the efficacy and safety of rimegepant 75 mg for the acute treatment of migraine in patients that are Hispanic or Latino (HL), non-HL White (nHLW), and non-HL Black/African American (nHLB/AA).</p><p><strong>Methods: </strong>Data were pooled from three multicenter, double-blind, randomized, placebo-controlled, phase 3 trials of rimegepant. Each study comprised a 28-day screening period, treatment phase (up to 45 days), and end of treatment visit within 7 days. Patients treated a single migraine attack of moderate to severe pain intensity during the treatment phase. Co-primary endpoints in the phase 3 trials were pain freedom and freedom from most bothersome symptom (MBS) both at 2 h post dose.</p><p><strong>Results: </strong>A total of 546 patients that are HL and 2872 patients that are non-HL (nHLW, n = 2215; nHLB/AA, n = 657) were enrolled. Patients that are HL exhibited a trend, but did not achieve statistical significance, with nominal p < 0.05 for pain freedom (PF) (19.9% rimegepant vs. 13.6% placebo, p = 0.051) or freedom from MBS (31.8% rimegepant vs. 31.8% placebo, p = 0.999), both at 2 h post dose. Exploratory analyses showed that patients that are nHLW and patients that are nHLB/AA achieved responses at 0.75-1.5 h and 1-2 h post dose, respectively, for pain relief, PF, and freedom from MBS, and these were maintained through 48 h. Responses for each were delayed in patients that are HL, starting at 3-4 h post dose and maintained through 48 h. Safety outcomes were similar across subgroups.</p><p><strong>Conclusion: </strong>Rimegepant was effective and safe for the acute treatment of migraine. Co-primary endpoints at 2 h post dose were not met in patients that are HL; exploratory analyses suggest that patients that are HL may experience a 1-2 h delayed response to rimegepant, with a greater proportion of patients that are HL having responded at 24-48 h post treatment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers: NCT03235479; NCT03237845; NCT03461757.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112887","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 Treatment Patterns Among Patients with Generalized Myasthenia Gravis in the United States.","authors":"Kavita Grover, Martin Cloutier, Geoffroy Coteur, Porpong Boonmak, Antoine C El Khoury, Maryia Zhdanava, Anabelle Tardif-Samson, Yuxi Wang, Kavita Gandhi","doi":"10.1007/s40120-026-01040-9","DOIUrl":"https://doi.org/10.1007/s40120-026-01040-9","url":null,"abstract":"<p><strong>Introduction: </strong>Conventional treatments for generalized myasthenia gravis (gMG) include acetylcholinesterase inhibitors (AChEi), systemic corticosteroids, and non-steroidal immunosuppressants; standard of care for exacerbation or myasthenic crisis includes immunoglobulin and plasmapheresis; newer advanced treatments include B-cell depleting agents, complement-5 inhibitors (C5i), and neonatal Fc receptor (FcRn) blockers. This study described real-world treatment patterns with currently available therapies and prevalence of myasthenia gravis (MG)-related clinical events (exacerbations or crises) among patients with gMG in the US.</p><p><strong>Methods: </strong>Adults with gMG were identified from Komodo Research Data (January 1, 2017-February 28, 2025). Index date was the first MG diagnosis by a neurologist. Patients were followed for ≥ 12 months post-index. Treatment sequencing was characterized by individual classes and broader treatment types (conventional treatments, advanced immunotherapies, immunoglobulin). A treatment episode was defined based on treatment changes (discontinuation, switch, augmentation/add-on, or drop), with any remaining or newly initiated/added treatment marking a new episode. Prevalence of MG-related clinical events was also described.</p><p><strong>Results: </strong>A total of 8759 patients were included (mean age: 61.5 years; 48.7% female; mean follow-up: 36.5 months). From the first (n = 7986) to fifth (n = 3340) treatment episode, AChEi use declined (80.3→57.6%), systemic corticosteroid use was consistent (49.0→63.0%), and use increased for non-steroidal immunosuppressants (12.7→40.2%), immunoglobulin (6.1→14.5%), rituximab (0.3→2.1%), C5i (0.3→3.4%), and FcRn blockers (0.3→3.8%). Conventional treatments were most frequently used in all episodes; advanced treatment use increased progressively from the first to fifth episodes, with initiation averaging 13.6-19.0 months post-diagnosis. Overall, 48.6% of patients experienced MG-related clinical events during follow-up, usually within the first year following gMG diagnosis (39.9%).</p><p><strong>Conclusion: </strong>Conventional treatments were the predominant initial strategy for gMG, while immunoglobulin and advanced treatments became more common over successive treatment episodes. The high prevalence of MG-related clinical events within the first year post-gMG diagnosis, despite treatment with conventional therapies, suggests the need for more effective and earlier interventions.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112482","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":"Narcolepsy and Idiopathic Hypersomnia Real-World Treatment Patterns and Changes in Alerting Agent Use After Low-Sodium Oxybate Initiation: A Retrospective Claims Analysis.","authors":"Sarah C Markt, Marisa Whalen, Jessica K Alexander, Caroleen Drachenberg, Natalie Gavrielov-Yusim, Silky Beaty, Elizabeth M Poole, John Kroner, Dionna Attinson, Shaina Desai, Jed Black, Michael J Thorpy","doi":"10.1007/s40120-026-01046-3","DOIUrl":"https://doi.org/10.1007/s40120-026-01046-3","url":null,"abstract":"<p><strong>Introduction: </strong>Various medications are prescribed to treat narcolepsy and idiopathic hypersomnia (IH), including low-sodium oxybate (LXB) and alerting agents (AAs; i.e., stimulants and wake-promoting agents). This study assessed treatment patterns in individuals with narcolepsy/IH, as well as changes in AA utilization following LXB initiation.</p><p><strong>Methods: </strong>Optum^® Market Clarity data were used to examine individuals aged ≥ 7 years with narcolepsy and individuals aged ≥ 18 years with IH. Treatment patterns were assessed following index until the end of the study period (07/2007-09/2023) and in the post-LXB approval period (narcolepsy: 07/2020-09/2023; IH: 08/2021-09/2023). Changes in AA treatment in the 180 days following LXB initiation were evaluated. Data were analyzed descriptively.</p><p><strong>Results: </strong>The narcolepsy cohort included 43,252 individuals (mean [SD] age 42.8 [17.2] years; 62.9% female). In the total and post-LXB (n = 10,220) follow-up periods, 30.9% and 35.3%, respectively, did not receive any treatment of interest. The most frequent first-line treatments were AAs (total follow-up: 52.9%; 76.5% among those treated; post-LXB period: 49.3%; 76.1% among those treated). Among 788 individuals with AA treatment prior to LXB initiation, 42.9% experienced AA discontinuation or reduction following LXB initiation. The IH cohort included 24,528 individuals (mean [SD] age 45.8 [15.7] years; 61.7% female). In the total and post-LXB (n = 2971) follow-up periods, 54.1% and 50.3%, respectively, did not receive any treatment of interest. The most frequent first-line treatments were AAs (total follow-up: 31.2%; 67.9% among those treated; post-LXB period: 36.2%; 72.9% among those treated). Among 96 individuals with AA treatment prior to LXB initiation, 53.1% experienced AA discontinuation or reduction following LXB initiation.</p><p><strong>Conclusion: </strong>Numerous treatment trajectories were observed after narcolepsy/IH diagnosis, highlighting the complexity in treating these conditions. Many individuals did not receive any treatment over the total follow-up period, which may indicate a treatment gap. AA discontinuation or reduction was common following LXB initiation.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112130","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":"Artificial Intelligence for Gadolinium-Sparing Detection of Active Multiple Sclerosis Lesions: A Structured Narrative Review.","authors":"Elham Moases Ghaffary, Omid Mirmosayyeb, Saeedeh Mirbagheri","doi":"10.1007/s40120-026-01030-x","DOIUrl":"https://doi.org/10.1007/s40120-026-01030-x","url":null,"abstract":"<p><strong>Introduction: </strong>Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI; T1c+) remains the reference standard for identifying active inflammatory lesions in multiple sclerosis (MS). However, cumulative exposure raises concerns regarding tissue deposition, cost, scan duration, and patient burden. Artificial intelligence (AI) has emerged as a potential strategy to reduce reliance on contrast administration.</p><p><strong>Methods: </strong>We conducted a structured narrative review of studies evaluating AI-based approaches for detecting active MS lesions without routine gadolinium use. Eligible studies included those that generated synthetic contrast-equivalent images or directly classified lesion activity using non-contrast MRI. Outcomes included diagnostic test accuracy, reconstruction fidelity, model characteristics, and methodological quality, which were assessed using an adapted QUADAS-2 framework.</p><p><strong>Results: </strong>Among studies reporting diagnostic accuracy against a gadolinium reference standard, sensitivity ranged from 72% to 100% and specificity from 66% to 96%. Only one study reported a complete contingency table; a second reported confusion matrices that are not reproduced here, and only one classifier included external multicenter validation. Image-synthesis studies demonstrated visually plausible outputs but were frequently validated against non-gadolinium targets, limiting clinical applicability. Common limitations included lack of prospective validation, limited reporting transparency, and insufficient evaluation of generalizability.</p><p><strong>Conclusion: </strong>AI-based approaches demonstrate feasibility for gadolinium-sparing MS imaging but are not yet sufficient to replace contrast-enhanced MRI in routine clinical practice. A plausible near-term role is as a triage tool to identify low-risk follow-up examinations in which gadolinium administration may be deferred. Prospective multicenter studies with standardized reporting and true post-contrast reference standards are needed before clinical adoption.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112844","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":"Horizon Scanning of Multiple Sclerosis Expenditure in Italy (2025-2029): Updated Insights from the Oracle Model.","authors":"Diego Centonze, Massimiliano Calabrese, Eleonora Cocco, Roberta Di Turi, Andrea Marcellusi, Andrea Marinozzi, Maria Vittoria Azzi, Alessandro Carrera, Francesca Donnaloja, Francesco Patti","doi":"10.1007/s40120-026-01042-7","DOIUrl":"https://doi.org/10.1007/s40120-026-01042-7","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic and progressively disabling neurological disease associated with a substantial clinical and socioeconomic burden. The introduction of an increasing number of new innovative therapies has further intensified concerns regarding the long-term sustainability for the Italian National Healthcare Service (NHS). Despite substantial therapeutic progress in MS management, with several treatments available for most MS patient populations, no definitive cure is currently available, and a critical therapeutic gap persists for non-relapsing secondary progressive MS (NR-SPMS), for which no approved treatments are specifically indicated. The objective of the present research is to estimate the Italian NHS expenditure for MS disease-modifying therapies (DMTs) between 2025 and 2029.</p><p><strong>Methods: </strong>Building on a published horizon-scanning model (i.e., Oracle), this study updates projections of expenditure and treatment patterns for MS DMTs through 2029, integrating clinical inputs (i.e., treated patients, patient shares for each reimbursed therapy) with economic inputs (i.e., annual therapy costs). Assumptions and input data were derived from IQVIA® proprietary databases and informed by clinical and pharmacoeconomic expert inputs. Results were validated in a multi-stakeholder roundtable.</p><p><strong>Results: </strong>This study shows that the number of treated patients is projected to rise to about 77,000 by 2029, i.e., approximately + 10% from 2024. Traditional platform therapies are projected to decrease by more than ten percentage points between 2024 and 2029, reflecting a shift toward high-efficacy and innovative therapies. New options include Bruton's tyrosine kinase (BTK) inhibitors (e.g., tolebrutinib, fenebrutinib, remibrutinib), projected to reach approximately 16% patient share within 3 years of first launch.</p><p><strong>Conclusion: </strong>Despite higher patient volumes and new launches, total DMT expenditure is expected to decline from €784 million in 2024 to €622 million in 2029, mainly driven by losses of exclusivity and price renegotiations. Results support the sustainability of the NHS and the reallocation of resources toward innovation, including innovative therapies for currently underserved populations such as NR-SPMS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112832","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":"Time Course of Rimegepant Effect for Acute Treatment of Migraine in Adults Unsuitable for Triptans: Exploratory Endpoints from a Phase 4, Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Michel Lanteri-Minet, Timothy Smith, Catherine Nalpas, Luz M Ramirez, Alexandra Thiry, Shannin McCollum, Sara Ramaker, Robert Fountaine","doi":"10.1007/s40120-026-01043-6","DOIUrl":"10.1007/s40120-026-01043-6","url":null,"abstract":"<p><strong>Introduction: </strong>A recent placebo-controlled trial (NCT05509400) demonstrated efficacy of single-dose rimegepant 75 mg for acute treatment of migraine in adults unsuitable for triptans. However, the full time course of rimegepant effect has not been reported for this study population.</p><p><strong>Methods: </strong>Pre-specified exploratory endpoints from study NCT05509400 assessed the percentage of participants with migraine pain relief, migraine pain freedom, return to normal function, and most bothersome symptom (MBS; nausea, photophobia, or phonophobia) freedom from 15 min to 48 h post-dose. Treatment comparisons used crude risk estimation with nominal p values.</p><p><strong>Results: </strong>Participants (rimegepant n = 286; placebo n = 284) were mostly female (89.3%) and had documented failure to ≥ 2 triptans with ≥ 1 reason due to prior intolerance (30.5%) or lack of efficacy (84.9%); 9.1% had a contraindication. Improvements of ≥ 5% for rimegepant over placebo with p ≤ 0.05 [difference (95% CI)] were first observed at 1 h for pain relief [8.6% (1.3%, 15.8%); p = 0.0201], 1.5 h for pain freedom [6.2% (1.5%, 11.0%); p = 0.0103] and return to normal function [7.1% (1.1%, 13.1%); p = 0.0210], and 2 h for MBS freedom [12.5% (5.4%, 19.5%); p = 0.0005]. Improvements of ≥ 5% over placebo were observed at all subsequent time points. Differences (95% CI) at 48 h were 31.2% (23.5%, 39.0%; p < 0.0001) for pain relief, 33.4% (25.9%, 40.9%; p < 0.0001) for pain freedom, 34.1% (25.8%, 42.5%; p < 0.0001) for return to normal function, and 23.2% (15.5%, 31.0%; p < 0.0001) for MBS freedom.</p><p><strong>Conclusion: </strong>In some patients unsuitable for triptans, rimegepant can provide rapid onset (within 1-2 h) of migraine symptom improvement. Improvements may be observed up to 48 h. Rimegepant may be appropriate when triptans are not suitable, particularly in individuals who failed triptans previously due to lack of efficacy. Graphical abstract available for this article.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT05509400.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112712","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}