Neurology and Therapy最新文献

{"title":"Long-Term Effectiveness of Galcanezumab in the Prevention of Migraine: An Italian Retrospective Analysis (REALITY).","authors":"Fabrizio Vernieri, Luigi Francesco Iannone, Simona Guerzoni, Antonio Russo, Piero Barbanti, Grazia Sances, Sabina Cevoli, Renata Rao, Carlo Lovati, Anna Ambrosini, Carlotta Buzzoni, Federico Battisti, Laura Vatteone, Steffy Martin Luther King, Federico Torelli","doi":"10.1007/s40120-024-00582-0","DOIUrl":"10.1007/s40120-024-00582-0","url":null,"abstract":"<p><strong>Background: </strong>Galcanezumab is approved in the European Union (EU) as migraine prophylaxis in adults with at least four migraine days per month. The aim of this retrospective observational study was to evaluate the long-term effectiveness of galcanezumab on migraine-related burdens and its impact on the use of healthcare resources for migraine prophylaxis in an Italian setting.</p><p><strong>Methods: </strong>This retrospective study was conducted in patients with migraine who initiated treatment with galcanezumab for migraine prevention between September 2019 and December 2020. Patient data for monthly migraine days (MMDs) and MMDs with acute medication intake were obtained by medical chart reviews. Information on patient-reported outcomes (using the Migraine Disability Assessment [MIDAS] questionnaire and Headache Impact Test 6 [HIT-6] questionnaire) and on the use of healthcare resources were also collected. The time points of interest were 1, 3, 6, 9, 12 months after the initiation of galcanezumab, and the most recent time point available during follow-up.</p><p><strong>Results: </strong>A total of 207 patients were enrolled in the study. Starting from month 3 after treatment initiation, more than half of the patients presented at least a 50% reduction in MMDs, and approximately one-third of non-responders at month 3 became responders at month 6. From month 3 to month 12, MMDs decreased on average by 10 days. Headache impact and disability, as well as migraine-associated health resource utilization decreased significantly during the treatment period. A positive significant association among the three dimensions of clinical burden (MMDs, MIDAS and days of acute medication intake) was also observed.</p><p><strong>Conclusion: </strong>The results of this Italian real-world study confirmed that galcanezumab has a rapid onset of effect and provides a long-term response among patients over different migraine-related burdens. The use of healthcare resources was also remarkably reduced.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703047","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":"Understanding the Symptoms and Impacts Experienced by People with Relapsing-Remitting MS: A Qualitative Investigation Using Semi-Structured Interviews.","authors":"Amy Barrett, Oyebimpe Olayinka-Amao, Tjalf Ziemssen, Trishna Bharadia, Christian Henke, Paul Kamudoni","doi":"10.1007/s40120-024-00584-y","DOIUrl":"10.1007/s40120-024-00584-y","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a disabling disease with unpredictable clinical manifestations. As clinical assessments may not fully capture the impact of MS on quality of life, they can be complemented by patient-reported outcome (PRO) measures to provide a more comprehensive picture of MS disease state and impact. The objectives of this study were to explore the experiences of people with relapsing-remitting MS, including symptoms and impacts on daily life, and to provide a conceptual model of MS outcomes.</p><p><strong>Methods: </strong>A literature review of studies that evaluated the experiences of people with MS was completed and combined with semi-structured concept elicitation interviews conducted with 14 people with relapsing-remitting MS in the USA.</p><p><strong>Results: </strong>The average age of the 14 participants was 43.9 (range 25-64) years, most were White (78.6%) and female (78.6%), and the mean duration since diagnosis was 6.6 (2-10) years. The most bothersome symptoms identified included fatigue (n = 9), cognitive dysfunction (n = 5), mobility/difficulty with walking (n = 3), and vision problems (n = 3). The most commonly reported impacts on daily life were balance problems/instability (n = 13), work life/productivity (n = 12), difficulty walking (n = 11), daily activities/household chores (n = 11), and leisure activities (n = 10).</p><p><strong>Conclusion: </strong>There was a high frequency of concepts associated with physical function, fatigue, and sensory-motor actions. A conceptual model was developed that captures the disease symptoms, impairments, and impacts identified in the interviews as well as known processes and symptoms identified in the literature search. This model underpins the appropriateness of PRO instruments, such as the PROMIS Fatigue (MS) 8a and PROMIS Physical Function (MS) 15a, which evaluate symptoms and impacts that matter most to people with MS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723485","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":"Safety and Tolerability of Combining CGRP Monoclonal Antibodies with Gepants in Patients with Migraine: A Retrospective Study.","authors":"Taoufik Alsaadi, Reem Suliman, Vanessa Santos, Ibrahim Al Qaisi, Princess Carmina, Batool Aldaher, Shadi Haddad, Yazan Bader","doi":"10.1007/s40120-024-00586-w","DOIUrl":"10.1007/s40120-024-00586-w","url":null,"abstract":"<p><strong>Introduction: </strong>The introduction of clacitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) has revolutionized the treatment of migraines. In clinical practice gepants might be considered as a valid option to treat acute attacks in patients with migraine who are treated with mAbs. However, the safety and tolerability of such a combination is not well addressed in the real-world setting. We designed this study to evaluate the safety and tolerability of combining CGRP mAbs with gepants in the management of migraines.</p><p><strong>Methods: </strong>This was a retrospective, real-world, exploratory study. The participants included within the study were adult (≥ 18 years) patients diagnosed with migraine. Screening for patients who were treated with at least one GCRP mAbs was done. Data was collected from one site, the American Center for Psychiatry and Neurology, Abu Dhabi UAE. A total of 516 patients taking CGRP mAbs were identified. Extracted data from patients' electronic medical records included patient demographics, migraine characteristics, prescribed treatments, and adverse events (AEs). The tolerability and safety of the combination therapy was evaluated on the basis of documented AEs.</p><p><strong>Results: </strong>Among the identified 516 patients, 234 were administered gepants in addition to the CRGP mAb (215, rimegepant; 19, ubrogepant). Eleven of the 234 patients switched from rimegepant to urogepant as a result of lack of efficacy; one patient switched from urogepant to zolmitriptan because of the lack of insurance coverage of the former medication. Among all the patients included in this study, three AEs were documented. These AEs were generally mild and transient and hence did not lead to discontinuation of treatment. Moreover, 42 of the 234 (17.9%) patients were switched from one class of CGRP mAbs to another at least once while continuing treatment with the assigned gepants.</p><p><strong>Conclusion: </strong>The findings of this study demonstrate that combining CGRP mAbs with gepants is a safe and well-tolerated treatment approach for migraine. Future studies are warranted to further validate these findings and explore long-term outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741530","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":"Acute Treatment of Migraine: Expert Consensus Statements from the United Arab Emirates (UAE).","authors":"Taoufik Alsaadi, Deeb M Kayed, Abubaker Al-Madani, Ali Mohamed Hassan, Derk Krieger, Naji Riachi, Pournamy Sarathchandran, Suhail Al-Rukn","doi":"10.1007/s40120-023-00576-4","DOIUrl":"10.1007/s40120-023-00576-4","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine, characterized by recurrent headaches and often accompanied by other symptoms like nausea, vomiting, and sensitivity to light and sound, significantly impacts patients' quality of life (QoL) and daily functioning. The global burden of migraines is reflected not only in terms of reduced QoL but also in the form of increased healthcare costs and missed work or school days. While UAE (United Arab Emirates)-specific consensus-based recommendations for the effective use of preventive calcitonin gene-related peptide (CGRP)-based migraine therapies have been published previously, an absence of such regional guidance on the management of acute migraine represents a gap that needs to be urgently addressed.</p><p><strong>Methods: </strong>A task force of eight neurologists from the UAE with expertise in migraine management conducted a comprehensive literature search and developed a set of expert statements on the management of acute migraine that were specific to the UAE context. To ensure diverse perspectives are considered, a Delphi panel comprising 16 neurologists plus the task force members was set up. Consensus was achieved using a modified Delphi survey method. Consensus was predefined as a median rating of 7 or higher without discordance (if > 25% of the Delphi panelists rate an expert statement as 3 or lower on the Likert scale). Expert statements achieving consensus were adopted.</p><p><strong>Results: </strong>The Modified Delphi method was used successfully to achieve consensus on all nine expert statements drafted by the task force. These consensus statements aim to provide a comprehensive guide for UAE healthcare professionals in treating acute migraine. The statements cover all aspects of acute migraine treatment, including what goals to set, the timing of treatment, treatment strategy to use in case of inadequate response to triptans, safety aspects of combining gepants for acute attacks with preventive CGRP-based therapies, special population (pregnant and pediatric patients) considerations, and the management of the most bothersome symptoms (MBS).</p><p><strong>Conclusions: </strong>Adopting these consensus statements on the treatment of acute migraine can help enhance patient care, improve outcomes, and standardize treatment practices in the UAE. The collaborative effort of experts with diverse experiences in developing these consensus statements will strengthen the credibility and applicability of these statements to various healthcare settings in the country.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491442","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":"Impact of Istradefylline on Levodopa Dose Escalation in Parkinson's Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study.","authors":"Taku Hatano, Renpei Sengoku, Hiroshi Nagayama, Naotake Yanagisawa, Asako Yoritaka, Keisuke Suzuki, Noriko Nishikawa, Yohei Mukai, Kyoichi Nomura, Norihito Yoshida, Morinobu Seki, Miho Kawabe Matsukawa, Hiroo Terashi, Katsuo Kimura, Jun Tashiro, Shigeki Hirano, Hidetomo Murakami, Hideto Joki, Tsuyoshi Uchiyama, Hideki Shimura, Kotaro Ogaki, Jiro Fukae, Yoshio Tsuboi, Kazushi Takahashi, Toshimasa Yamamoto, Kenichi Kaida, Ryoko Ihara, Kazutomi Kanemaru, Osamu Kano","doi":"10.1007/s40120-023-00574-6","DOIUrl":"10.1007/s40120-023-00574-6","url":null,"abstract":"<p><strong>Introduction: </strong>A higher levodopa dose is a risk factor for motor complications in Parkinson's disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off.</p><p><strong>Methods: </strong>This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300-400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes.</p><p><strong>Results: </strong>The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group.</p><p><strong>Conclusion: </strong>IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD.</p><p><strong>Trial registration: </strong>Japan Registry of Clinical Trials: jRCTs031180248.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472789","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":"Monitoring of Perioperative Microcirculation Dysfunction by Near-Infrared Spectroscopy for Neurological Deterioration and Prognosis of Aneurysmal Subarachnoid Hemorrhage: An Observational, Longitudinal Cohort Study.","authors":"Shunyan Yang, Binbin Tan, Jie Lin, Xia Wang, Congying Fu, Kaishan Wang, Jinyu Qian, Jin Liu, Jishu Xian, Liang Tan, Hua Feng, Yujie Chen, Lihua Wang","doi":"10.1007/s40120-024-00585-x","DOIUrl":"10.1007/s40120-024-00585-x","url":null,"abstract":"<p><strong>Introduction: </strong>No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH.</p><p><strong>Methods: </strong>A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO₂) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH.</p><p><strong>Results: </strong>Our data suggest that the rSO₂ is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO₂ during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators.</p><p><strong>Conclusions: </strong>The rSO₂ concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898162","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":"Population Pharmacokinetic Analysis to Support and Facilitate Switching from Risperidone Formulations to Rykindo in Patients with Schizophrenia.","authors":"Wenyan Wang, Xiaofeng Wang, Ying Dong, David P Walling, Pinglan Liu, Wanhui Liu, Yanan Shi, Kaoxiang Sun","doi":"10.1007/s40120-024-00578-w","DOIUrl":"10.1007/s40120-024-00578-w","url":null,"abstract":"<p><strong>Introduction: </strong>RYKINDO® (Rykindo) is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This analysis was conducted to demonstrate that the clinical outcomes of Rykindo are equivalent to those of RISPERDAL CONSTA® (Consta; Q2W), and to establish a dosing methodology to switch from Consta to Rykindo, as well as to introduce Rykindo to patients who are currently on oral RISPERDAL® (Risperdal).</p><p><strong>Methods: </strong>Population pharmacokinetic (PK) models for Rykindo and Consta were developed using a nonlinear mixed-effects model with the data from phase 1 studies. A model-based simulation was also conducted using NONMEM.</p><p><strong>Results: </strong>The PK profiles of Rykindo and Consta were adequately represented by a one-compartment model with an immediate release followed by an intermediate and third main release. Drug release of Rykindo was faster than for Consta, reaching steady state approximately 2-3 weeks earlier. The exposures of the active moiety of Rykindo and Consta were comparable at steady state. Model-based simulation indicated that switching from Consta to Rykindo requires administration of the first Rykindo injection within 4-5 weeks following the last Consta injection. For patients taking Risperdal, introducing Rykindo with 1 week of Risperdal supplemental for once-daily dosing (QD) can achieve comparable or superior exposure to that of Consta with 3 weeks of oral QD supplements. A dosing window of ± 3 days for Rykindo was recommended.</p><p><strong>Conclusions: </strong>This established approach provides guidance to physicians to initiate Rykindo therapy in adult patients with schizophrenia.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT02055287, NCT02186769 and NCT02091388.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513438","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":"Textbook Outcomes Among Patients with Aneurysmal Subarachnoid Hemorrhage Following Endovascular Treatment.","authors":"Zisheng Liu, Yuhao Tan, Yanpeng Wei, Dongwei Dai, Rui Zhao, Qiang Li, Qinghai Huang, Yi Xu, Pengfei Yang, Jun Sun, Jianmin Liu, Qiao Zuo","doi":"10.1007/s40120-024-00577-x","DOIUrl":"10.1007/s40120-024-00577-x","url":null,"abstract":"<p><strong>Introduction: </strong>The case fatality rate among patients with aneurysmal subarachnoid hemorrhage (aSAH) has decreased progressively, with numerous patients subjected to contemporary paradigms that minimize the use of agonizing therapeutic processes. The concept of the \"Textbook Outcome\" (TO), a composite outcome that highlights numerous favorable outcomes, was developed in the context of gastrointestinal tumor surgeries and expeditiously extended across diverse surgical spheres. The aim of this study was to explore the factors hindering the achievement of optimal prognoses in postinterventional aSAH patients, employ textbook outcomes, and establish predictive models.</p><p><strong>Methods: </strong>We conducted a retrospective review of data from 1270 aSAH patients who received endovascular treatment between 2012 and 2018. We delineated an exemplary TO within the aSAH domain, characterized by favorable clinical results, minimal complications, and the absence of retreatments. This TO-oriented approach is explained within the manuscript.</p><p><strong>Results: </strong>The findings revealed that preoperative intraventricular hemorrhage (IVH), preoperative Hunt and Hess grade (H&H) ≥ 3, World Federation of Neurosurgical Societies (WFNS) grade ≥ 3, the presence of blebs on the aneurysm, aneurysms situated at branching sites, and non-stent-assisted endovascular intervention were the strongest risk factors for not achieving textbook outcomes (non-\"Textbook Outcome\" [N-TO]). Decision curve analysis and calibration analyses revealed strong concordance between the predictions of the N-TO nomogram model and the actual observations.</p><p><strong>Conclusions: </strong>Treatment Outcomes hold significant practical value in clinical studies of aSAH patients receiving endovascular treatment. The likelihood of N-TOs was predicted by IVH, H&H grade ≥ 3, WFNS grade ≥ 2, presence o f bleb on the aneurysm, and aneurysms located at branching sites.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542874","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":"Conversion to Brivaracetam Monotherapy in Clinical Practice: A Retrospective Study.","authors":"Simona Lattanzi, Nicoletta Foschi, Chiara Martellino, Daniela Audenino, Giovanni Boero, Paolo Bonanni, Edoardo Ferlazzo, Valentina Chiesa, Filippo Dainese, Marta Piccioli, Alessandra Ferrari, Angelo Labate","doi":"10.1007/s40120-024-00580-2","DOIUrl":"10.1007/s40120-024-00580-2","url":null,"abstract":"<p><strong>Introduction: </strong>The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice.</p><p><strong>Methods: </strong>This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months. Secondary outcomes included the 6- and 12-month rates of seizure freedom. Safety and tolerability outcomes included the frequency and type of adverse events (AEs) and the occurrence of treatment discontinuation due to AEs.</p><p><strong>Results: </strong>A total of 44 participants with a median age of 63.5 (interquartile range 44-73.5) years were included; 17 subjects were seizure free at baseline, and 9 of them switched from levetiracetam because of lack of tolerability. The retention rate of BRV monotherapy was 88.6% (39/44) at 6 months and 83.9% (26/31) at 12 months. The rates of seizure freedom were 72.7% (32/44) in subjects with 6-month follow-up and 58.1% (18/31) in subjects with 12-month follow-up. The median maintenance dosage of BRV monotherapy was 150 (100-200) mg/day at 6 months and 125 (100-200) mg/day in subjects with 12-month follow-up. Adverse events were recorded in 6/44 (13.6%) participants and led to BRV discontinuation in 2/44 (4.5%) cases. The reported AEs were somnolence (n = 3), fatigue (n = 2), and irritability (n = 1); no serious AEs were experienced. In 21/44 (47.7%) participants, BRV monotherapy resulted from the direct switch from levetiracetam. The rates of treatment retention and seizure freedom at 6 and 12 months were higher among people who switched from levetiracetam to BRV monotherapy.</p><p><strong>Conclusion: </strong>Brivaracetam may be a valuable treatment of focal seizures in people who converted to monotherapy in a real-life setting.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651250","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":"Bioequivalence Study of Two Tablet Formulations of Clonazepam 2 mg: A Randomized, Open-Label, Crossover Study in Healthy Mexican Volunteers Under Fasting Conditions.","authors":"Luis Genis-Najera, Maria Elena Sañudo-Maury","doi":"10.1007/s40120-023-00567-5","DOIUrl":"10.1007/s40120-023-00567-5","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of neurological disorders is high among the Mexican population. Clonazepam is primarily indicated to treat panic disorders, certain kinds of epilepsy such as status epilepticus, childhood motor seizures (petit mal absence, Lennox-Gastaut syndrome, and infantile spasms), anxiety, and muscle spasm. This study was performed to compare bioequivalence between two oral tablet formulations of clonazepam 2 mg in healthy Mexican volunteers under fasting conditions.</p><p><strong>Methods: </strong>This phase I, randomized, open-label, two-treatment, crossover study included 30 healthy volunteers. Subjects were randomly assigned to either test or reference formulation of clonazepam 2 mg. Each study period was separated by 21-day washout period. Blood samples were collected at pre-dose and up to 72 h after drug administration. Clonazepam concentrations were determined using a validated ultra-flow liquid chromatography-tandem mass spectrometric method. Pharmacokinetic parameters were determined using a non-compartmental method. Two formulations were considered bioequivalent if geometric mean ratios (test/reference) were between 80% and 125%. Safety was evaluated by recording adverse events.</p><p><strong>Results: </strong>Pharmacokinetic parameters were comparable between test and reference formulations. The mean maximum plasma concentration (C_max) was ≈ 13 ng/mL, area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC_0-t) was ≈ 360 ng h/mL, time to reach maximum plasma concentration (T_max) was ≈ 3 h, and elimination half-life (t_1/2) was ≈ 43 h. Geometric mean ratios (90% confidence interval) of C_max (99.2-115.3%), AUC_0-t (100.6-110.6%), and AUC_0-∞ (98.5-111.6%) were within the bioequivalence range. Seven non-serious adverse events (mostly asymptomatic hypotension) were recorded.</p><p><strong>Conclusion: </strong>The test and reference formulations of clonazepam 2 mg were bioequivalent and well tolerated in healthy Mexican volunteers under fasting conditions.</p><p><strong>Protocol authorization number: </strong>213301410B0051 (Approved on April 13, 2021).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470644","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}