Neurology and Therapy最新文献

{"title":"Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia.","authors":"Itay Perlstein, Avia Merenlender Wagner, Anna Elgart, Anthe S Zandvliet, Farina Hellmann, YuWei Lin, Eline van Maanen, Nele Plock, Floris Fauchet, Rajendra Singh","doi":"10.1007/s40120-025-00723-z","DOIUrl":"https://doi.org/10.1007/s40120-025-00723-z","url":null,"abstract":"<p><strong>Introduction: </strong>TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was to characterize the pharmacokinetics (PK) of TV-46000 based on pooled data from phase 1 and phase 3 studies, and to further support clinical use aspects of TV-46000.</p><p><strong>Methods: </strong>A population PK (popPK) model was developed using TV-46000 PK data obtained from three phase 1 studies (n = 267) and two phase 3 trials (n = 425). A sequential parent-metabolite model structure was used, and the total active moiety (TAM) concentration-time profiles were simulated for TV-46000 once monthly (q1m) and once every 2 months (q2m) across the range of available doses and different administration sites.</p><p><strong>Results: </strong>The popPK model adequately characterized the PK of risperidone and its active metabolite. TV-46000 reaches therapeutic plasma TAM concentrations (≥ 10 ng/mL) within 24 h following first dose administration. Three months after initiation of TV-46000, 86% and 88% of steady-state TAM exposure were achieved for q1m and q2m, respectively, and steady state was fully attained by 6 months (i.e., > 90% of steady-state TAM exposure). In addition, simulated D2 receptor occupancy for TV-46000 was generally within the therapeutic window of 60-80% during both dosing intervals.</p><p><strong>Conclusions: </strong>The developed popPK model, together with corresponding simulations, supports TV-46000 as a LASCA that offers flexible dosing intervals (q1m or q2m) and administration sites (abdomen or upper arm) and does not require oral supplementation or loading dose(s).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692601","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":"Therapies for Advanced Parkinson's Disease in Sweden: A Cost-Effectiveness Analysis Using Real-World Data.","authors":"Dag Nyholm, Simon Eggington, Astrid Holm","doi":"10.1007/s40120-025-00730-0","DOIUrl":"https://doi.org/10.1007/s40120-025-00730-0","url":null,"abstract":"<p><strong>Introduction: </strong>The Swedish Parkinson's Disease (PD) Registry provides rich data on cost and quality of life for patients receiving device-aided therapies (DATs) for Parkinson's disease in Sweden. This study sought to use this real-world evidence to determine the cost-effectiveness profile of specific DATs in Sweden.</p><p><strong>Methods: </strong>We developed a state transition (Markov) model to represent disease progression over time and used published clinical data to represent short- and long-term disease outcomes. We used data from the Swedish PD Registry to assign costs and quality of life measures (utilities) to each health state and modelled total costs and outcomes over a 20-year time horizon. The four treatment groups modelled were: best medical therapy, deep brain stimulation, levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion. We calculated results from both payer and societal perspectives.</p><p><strong>Results: </strong>The most cost-effective intervention was deep brain stimulation (DBS), which dominated all other interventions. Sensitivity analysis indicated that the key drivers of uncertainty were the transition probabilities between successive Hoehn and Yahr stages on each treatment. Results were consistent from both payer and societal perspectives.</p><p><strong>Conclusion: </strong>DBS is a cost-effective use of resources in Sweden. However, uncertainty remains regarding long-term symptom control as well as quality of life within specific health states for all device-aided therapies, and further data are needed to fully validate the model projections and provide more insight into areas of future research.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673445","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":"Sudoscan in ATTRv Amyloidosis: A Potential Marker of Disease Progression?","authors":"Angela Romano, Valeria Guglielmino, Francesca Vitali, Maria Ausilia Sciarrone, Giovanni Siconolfi, Andrea Di Paolantonio, Guido Primiano, Marco Luigetti","doi":"10.1007/s40120-025-00721-1","DOIUrl":"https://doi.org/10.1007/s40120-025-00721-1","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a severe, autosomal dominant disease resulting from multisystemic extracellular deposition of amyloid fibrils, leading to progressive organ damage and death. Sudoscan is a reproducible tool investigating sweat gland function and, indirectly, small nerve fiber impairment. The aim of this study was to evaluate any changes over time in electrochemical skin conductance (ESC) measured by Sudoscan in a cohort of late-onset patients with ATTRv from a single Italian center. Additionally, we investigated the role of Sudoscan as a marker of disease severity to confirm previous literature data.</p><p><strong>Methods: </strong>We enrolled 61 patients with a late-onset ATTRv amyloidosis harboring different TTR variants with at least one clinical and instrumental evaluation including Sudoscan. Correlations with clinical data (including both clinical scales and questionnaires) were investigated to confirm the role of Sudoscan as a marker of disease severity. Moreover, a longitudinal analysis was performed in the subgroup of patients with at least 4 complete yearly evaluations (n = 23) to assess the role of Sudoscan as a marker of disease progression.</p><p><strong>Results: </strong>At each yearly assessment, ESC values from both feet and hands significantly correlated with disease duration and neuropathy severity, as assessed by common clinical scales and questionnaires. No correlation was found with age at evaluation. Moreover, we observed a statistically significant change over time in ESC values measured at the feet (fESC) but not at the hands (hESC).</p><p><strong>Conclusions: </strong>Sudoscan may represent a reliable marker of dysautonomia in ATTRv amyloidosis, displaying a potential role as a marker of both disease severity and progression. It could, therefore, serve as an outcome measure in future clinical trials. In addition, feet ESC seems to be a significant, independent predictor of autonomic dysfunction.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649707","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":"Menopause, Perimenopause, and Migraine: Understanding the Intersections and Implications for Treatment.","authors":"Marta Waliszewska-Prosół, Giovanni Grandi, Raffaele Ornello, Bianca Raffaelli, Marcin Straburzyński, Claudio Tana, Paolo Martelletti","doi":"10.1007/s40120-025-00720-2","DOIUrl":"https://doi.org/10.1007/s40120-025-00720-2","url":null,"abstract":"<p><p>Migraine affects women three times more often than it does men, and various mechanisms may explain this incidence, including the key role of female sex hormones. Fluctuations in the levels of these hormones and their feedback control regulate the menstrual cycle, pregnancy, puerperium, perimenopause, and menopause. They can influence the occurrence and severity of migraine throughout the reproductive period. Of particular importance seems to be the perimenopausal period, which is associated with an increase in migraine, especially menstrual migraine, which is considered more disabling and less amenable to treatment than non-menstrual attacks. This article reviews the available evidence documenting the relationship between perimenopause, menopause, and migraine and diagnostic considerations in an attempt to determine the management of these periods of a woman's life. Special considerations, future directions, and unmet needs for perimenopausal and menopausal migraine are also discussed.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630690","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":"Adjunctive Brivaracetam in People with Epilepsy and Intellectual Disability: Evidence from the BRIVAracetam Add-On First Italian netwoRk Study.","authors":"Simona Lattanzi, Laura Canafoglia, Maria Paola Canevini, Sara Casciato, Emanuele Cerulli Irelli, Valentina Chiesa, Filippo Dainese, Giovanni De Maria, Giuseppe Didato, Giancarlo Di Gennaro, Giovanni Falcicchio, Martina Fanella, Edoardo Ferlazzo, Massimo Gangitano, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Federico Piazza, Chiara Pizzanelli, Patrizia Pulitano, Federica Ranzato, Eleonora Rosati, Laura Tassi, Carlo Di Bonaventura","doi":"10.1007/s40120-025-00717-x","DOIUrl":"https://doi.org/10.1007/s40120-025-00717-x","url":null,"abstract":"<p><strong>Introduction: </strong>Subjects with intellectual disability are usually excluded from clinical trials and there is limited evidence-based guidance for the choice of antiseizure medications in this vulnerable population. The study explored the effectiveness of brivaracetam (BRV) in people with epilepsy and intellectual disability.</p><p><strong>Methods: </strong>BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST) was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The occurrence of adverse events (AEs) was also considered. Analyses by the presence and severity of intellectual disability were performed.</p><p><strong>Results: </strong>Subjects with intellectual disability were 253 (24.6%) out of 1029 participants. The 12-month rates of seizure freedom were 18.4% and 10.3% in participants without and with intellectual disability, respectively; the corresponding values for seizure response were 40.0% and 28.9%. Intellectual disability was not an independent predictor of seizure outcomes. The rates of treatment discontinuation were 25.8% and 26.4% in participants without and with intellectual disability. respectively. There were no statistically significant differences in the rates of any AEs, somnolence, nervousness/agitation, and aggressiveness by the presence and degree of intellectual disability.</p><p><strong>Conclusion: </strong>Brivaracetam can be a suitable treatment option and offer opportunities for clinical improvement in subjects with intellectual disability and uncontrolled seizures.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605740","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":"Factors Influencing the Response of Patients with Infantile Epileptic Spasms Syndrome to ACTH as Repeated First-Line Therapy.","authors":"Wenrong Ge, Ping Pang, Ziyan Zhang, Lin Wan, Guang Yang","doi":"10.1007/s40120-025-00722-0","DOIUrl":"https://doi.org/10.1007/s40120-025-00722-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The treatment of infantile epileptic spasms syndrome (IESS) aims to achieve spasm control. Current first-line interventions include hormone therapy (adrenocorticotropic hormone [ACTH] and corticosteroids) and vigabatrin. Despite treatment, the response rate remains at around 40%, with some infants experiencing relapse after achieving initial spasm control. In certain cases, a second course of first-line therapy may be warranted. The objective of this study was to perform a secondary analysis of data from our previously published studies to elucidate factors influencing the efficacy of ACTH following its re-administration after the lack of response to the initial first-line treatment or relapse.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective analysis of clinical data from children with IESS who had experienced treatment failure or relapse following initial first-line therapy and who subsequently received ACTH at our institution as a second first-line treatment. We examined such variables as etiological classification, interval between treatments, age at first epileptic seizure, radiological findings, and changes in pharmacological treatment modalities, with the overall aim to assess the impact of these variables on the short-term response (disappearance of spasms for &gt; 4 weeks and without hypsarrhythmia pattern) to the second administration of the first-line therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 128 patients with IESS identified and included in the analysis, 50 (39.1%) achieved a short-term response. Comparative analysis indicated that responders had a shorter duration between the initial first-line therapy and the initiation of the second first-line treatment (median 1.00 [interquartile range {IQR} 0.00, 2.00] vs. 1.75 [IQR 0.50, 3.88] months), were younger at the time of the second first-line treatment (median 11 [IQR 8, 17] vs. 16 [IQR 10, 24] months, p = 0.008), and were less likely to present with additional seizure types during spasm episodes (12.0% vs. 28.2%, p = 0.030). A multifactorial regression model indicated that older age at first seizure and a short-term response to initial first-line treatment were associated with a higher likelihood of obtaining an initial response in the subsequent ACTH treatment (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.39, 7.23, p = 0.014 and OR 5.41, 95% CI 1.48, 23.90, p = 0.016, respectively). Conversely, an older age at the time of the initial first-line treatment, an older age at the onset of epileptic spasms, and patients with congenital structural abnormalities without genetic abnormalities were less likely to achieve an initial response in subsequent ACTH treatment (OR 0.85, 95% CI 0.78, 0.92, p &lt; 0.001; OR 0.43, 95% CI 0.16, 0.82, p = 0.032; and OR 0.18, 95% CI 0.04, 0.69, p = 0.016, respectively)..&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;A second ACTH therapy regimen (second first-line treatment) may help some children with IESS who d","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597040","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":"Lecanemab's Path Forward: Navigating the Future of Alzheimer's Treatment in Europe Amidst the EMA's Rejection.","authors":"Alessandro Martorana, Chiara Giuseppina Bonomi, Martina Gaia Di Donna, Caterina Motta","doi":"10.1007/s40120-024-00675-w","DOIUrl":"10.1007/s40120-024-00675-w","url":null,"abstract":"<p><p>Lecanemab (Leqembi^©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1-5"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564810","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":"Development and Validation of a Novel Classification System and Prognostic Model for Open Traumatic Brain Injury: A Multicenter Retrospective Study.","authors":"Yuhui Chen, Li Chen, Liang Xian, Haibing Liu, Jiaxing Wang, Shaohuai Xia, Liangfeng Wei, Xuewei Xia, Shousen Wang","doi":"10.1007/s40120-024-00678-7","DOIUrl":"10.1007/s40120-024-00678-7","url":null,"abstract":"<p><strong>Introduction: </strong>Open traumatic brain injury (OTBI) is associated with high mortality and morbidity; however, the classification of these injuries and the determination of patient prognosis remain uncertain, hindering the selection of optimal treatment strategies. This study aimed to develop and validate a novel OTBI classification system and a prognostic model for poor prognosis.</p><p><strong>Methods: </strong>This retrospective study included patients with isolated OTBI who received treatment at three large medical centers in China between January 2020 and June 2022 as the training set. Data on patients with OTBI collected at the Fuzong Clinical Medical College of Fujian Medical University between July 2022 and June 2023 were used as the validation set. Clinical parameters, including clinical data at admission, radiological and laboratory findings, details of surgical methods, and prognosis were collected. Prognosis was assessed through a dichotomized Glasgow Outcome Scale (GOS). A novel OTBI classification was proposed, categorizing patients based on a combination of intracranial hematoma and midline shift observed on imaging, and logistic regression analyses were performed to identify risk factors associated with poor prognosis and to investigate the association between the novel OTBI classification and prognosis. Finally, a nomogram suitable for clinical application was established and validated.</p><p><strong>Results: </strong>Multivariable logistic regression analysis identified OTBI classification type C (p < 0.001), a Glasgow Coma Scale score (GCS) ≤ 8 (p < 0.001), subarachnoid hemorrhage (SAH) (p = 0.004), subdural hematoma (SDH) (p = 0.011), and coagulopathy (p = 0.020) as independent risk factors for poor prognosis. The addition of the OTBI classification to a model containing all the other identified prognostic factors improved the predictive ability of the model (Z = 1.983; p = 0.047). In the validation set, the model achieved an area under the curve (AUC) of 0.917 [95% confidence interval (CI) = 0.864-0.970]. The calibration curve closely approximated the ideal curve, indicating strong predictive performance of the model.</p><p><strong>Conclusions: </strong>The implementation of our proposed OTBI classification system and its use alongside the other prognostic factors identified here may improve the prediction of patient prognosis and aid in the selection of the most suitable treatment strategies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"157-175"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568318","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":"The Impact of Migraine on the Whole Life Course of Patients: Results from the OVERCOME (Japan) 2nd Study.","authors":"Daisuke Danno, Shiho Suzuki, Tsubasa Takizawa, Ryotaro Ishii, Masayuki Hamakawa, Yoshinori Tanizawa, Satoshi Osaga, Mika Komori","doi":"10.1007/s40120-024-00690-x","DOIUrl":"10.1007/s40120-024-00690-x","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of migraine on patients' lives, including challenges they face before getting access to appropriate medical management, is not well understood. The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE [OVERCOME (Japan)] 2nd study was conducted to provide information regarding burden and experience with migraine throughout the life course.</p><p><strong>Methods: </strong>This cross-sectional, population-based, nationwide online survey was conducted in adults with or without migraine. The migraine group reported their headache features and experiences in medical management since headache onset. Migraine's burden and impact were assessed with various PRO instruments. Migraine and non-migraine groups reported their experiences in life events and answered questions on self-esteem. Subgroup analyses by the number of monthly headache days (MHD) were performed.</p><p><strong>Results: </strong>The migraine group (n = 19,590) was numerically younger [mean (SD) age 40.5 (13.1) years vs. 53.1 (17.8) years] and included more females (68.8% vs. 52.1%) than the non-migraine group (n = 2219). The migraine group had mean (SD) 3.5 (5.2) MHDs; 24.2-56.7% had moderate-to-very severe disease burden per various PRO instruments. Headaches started when respondents with migraine were 17.8 years old; 86.7% started over-the-counter medications at 19.4 years of age. Only 46.4% self-reported migraine diagnosis by a physician and 25.1% received an oral preventive drug, almost a decade after headache onset. Up to 16.8% reported poor support/lack of understanding from either teachers or parents during school life. The migraine group had numerically more frequent job changes and divorce, and lower self-esteem, than the non-migraine group. Across assessments, increased MHDs tended to worsen outcomes.</p><p><strong>Conclusion: </strong>Migraine affected many individuals from an early stage, but timely support and medical intervention were insufficient. This may negatively impact important life events, cause long-term impairment, and decrease self-esteem. Hence, improving the social understanding and medical environment for migraine to provide timely support is essential.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"335-356"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872567","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":"Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.","authors":"Ramesh R Boinpally, Brian McNamee","doi":"10.1007/s40120-024-00699-2","DOIUrl":"10.1007/s40120-024-00699-2","url":null,"abstract":"<p><strong>Introduction: </strong>Atogepant is a calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults in the USA, EU, and several other countries. The objectives of this study were to evaluate the pharmacokinetics (PK) and dose proportionality of atogepant in healthy Japanese participants, evaluate the safety and tolerability of atogepant in Japanese participants, and explore the differences in the PK and safety of atogepant in Japanese vs white participants.</p><p><strong>Methods: </strong>A total of 50 participants (40 Japanese and 10 white) were enrolled into five cohorts; Japanese cohorts were randomized in a 4:1 ratio to atogepant (10 mg, 30 mg, or 60 mg daily dosing and 60 mg twice daily) or placebo. The white participants were randomized to atogepant (60 mg twice daily) or placebo. Doses were administered on day 1 and days 3-8, with those on days 1 and 8 administered after an overnight fast.</p><p><strong>Results: </strong>In Japanese participants, atogepant exposure increased with dose, and there was no accumulation with once-daily dosing and minimal (~ 20%) accumulation with twice-daily dosing. Atogepant steady-state exposure appeared to be marginally lower in Japanese participants compared with white participants and was well tolerated. There were no treatment-related adverse events, serious adverse events, clinically significant changes in vital signs, or signs of suicidal ideation or behaviors.</p><p><strong>Conclusion: </strong>Atogepant exposure increased with dose in healthy Japanese participants and was well tolerated within the dose range tested.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"399-412"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927511","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}