Pub Date : 2025-02-12DOI: 10.1007/s40120-024-00706-6
Paola Zaratin, Per Soelberg Sørensen, Óscar Fernández, Giancarlo Comi
Using the case study of the Multiple Sclerosis Care Unit Initiative launched by the European Charcot Foundation, we discuss the need to evaluate the impact of multidisciplinary and multi-stakeholder healthcare systems on patient-reported experience and outcomes for the programming and monitoring of brain and neurodegenerative diseases in Europe and beyond. The multiple sclerosis (MS) case study presented in this paper highlights the role of patient-generated data as indicators of the impact of value-based healthcare (VBHC) for all the different neurological diseases whose prodromal symptoms are the first signs of disease progression and therefore instrumental markers for preventive treatments to preserve brain health. A holistic approach to the treatment of MS plays a crucial role in the inclusion and scientific meaning of the patient's perspective in terms of patient-reported dimension and patient-generated health data (PGHD).
{"title":"Patient-Generated Data as Indicators of Impact of Multidisciplinary and Multi-stakeholder Health Care Systems, in the Age of Personalised Medicine.","authors":"Paola Zaratin, Per Soelberg Sørensen, Óscar Fernández, Giancarlo Comi","doi":"10.1007/s40120-024-00706-6","DOIUrl":"https://doi.org/10.1007/s40120-024-00706-6","url":null,"abstract":"<p><p>Using the case study of the Multiple Sclerosis Care Unit Initiative launched by the European Charcot Foundation, we discuss the need to evaluate the impact of multidisciplinary and multi-stakeholder healthcare systems on patient-reported experience and outcomes for the programming and monitoring of brain and neurodegenerative diseases in Europe and beyond. The multiple sclerosis (MS) case study presented in this paper highlights the role of patient-generated data as indicators of the impact of value-based healthcare (VBHC) for all the different neurological diseases whose prodromal symptoms are the first signs of disease progression and therefore instrumental markers for preventive treatments to preserve brain health. A holistic approach to the treatment of MS plays a crucial role in the inclusion and scientific meaning of the patient's perspective in terms of patient-reported dimension and patient-generated health data (PGHD).</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399690","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}
Pub Date : 2025-02-10DOI: 10.1007/s40120-025-00710-4
Chen Zhong, Kang Yang, Nianhua Wang, Liang Yang, Zhuanyi Yang, Lixin Xu, Jun Wang, Longbo Zhang
Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, affects millions worldwide, with a significant proportion resistant to pharmacological treatments. Surgical interventions have emerged as pivotal in managing drug-resistant epilepsy (DRE), aiming to reduce seizure frequency or achieve seizure freedom. Traditional resective surgeries have evolved with technological advances, enhancing precision and safety. Neurostimulation techniques, such as responsive neurostimulation (RNS) and deep brain stimulation (DBS), now provide personalized, real-time seizure management, offering alternatives to traditional surgery. Minimally invasive ablative methods, such as laser interstitial thermal therapy (LITT) and Magnetic Resonance-guided Focused Ultrasound (MRgFUS), allow for targeted destruction of epileptogenic tissue with reduced risks and faster recovery times. The use of stereo-electroencephalography (SEEG) and robotic assistance has further refined surgical precision, enhancing outcomes. These advancements mark a paradigm shift towards precision medicine in epilepsy care, promising improved seizure management and quality of life for patients globally. This review outlines the latest innovations in epilepsy surgery, emphasizing their mechanisms and clinical implications to improve outcomes for patients with DRE.
{"title":"Advancements in Surgical Therapies for Drug-Resistant Epilepsy: A Paradigm Shift towards Precision Care.","authors":"Chen Zhong, Kang Yang, Nianhua Wang, Liang Yang, Zhuanyi Yang, Lixin Xu, Jun Wang, Longbo Zhang","doi":"10.1007/s40120-025-00710-4","DOIUrl":"https://doi.org/10.1007/s40120-025-00710-4","url":null,"abstract":"<p><p>Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, affects millions worldwide, with a significant proportion resistant to pharmacological treatments. Surgical interventions have emerged as pivotal in managing drug-resistant epilepsy (DRE), aiming to reduce seizure frequency or achieve seizure freedom. Traditional resective surgeries have evolved with technological advances, enhancing precision and safety. Neurostimulation techniques, such as responsive neurostimulation (RNS) and deep brain stimulation (DBS), now provide personalized, real-time seizure management, offering alternatives to traditional surgery. Minimally invasive ablative methods, such as laser interstitial thermal therapy (LITT) and Magnetic Resonance-guided Focused Ultrasound (MRgFUS), allow for targeted destruction of epileptogenic tissue with reduced risks and faster recovery times. The use of stereo-electroencephalography (SEEG) and robotic assistance has further refined surgical precision, enhancing outcomes. These advancements mark a paradigm shift towards precision medicine in epilepsy care, promising improved seizure management and quality of life for patients globally. This review outlines the latest innovations in epilepsy surgery, emphasizing their mechanisms and clinical implications to improve outcomes for patients with DRE.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382856","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}
Pub Date : 2025-02-01Epub Date: 2024-11-04DOI: 10.1007/s40120-024-00678-7
Yuhui Chen, Li Chen, Liang Xian, Haibing Liu, Jiaxing Wang, Shaohuai Xia, Liangfeng Wei, Xuewei Xia, Shousen Wang
Introduction: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
{"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}
Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
{"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}
Pub Date : 2025-02-01Epub Date: 2025-01-04DOI: 10.1007/s40120-024-00699-2
Ramesh R Boinpally, Brian McNamee
Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: Atogepant exposure increased with dose in healthy Japanese participants and was well tolerated within the dose range tested.
{"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}
Pub Date : 2025-02-01Epub Date: 2024-11-11DOI: 10.1007/s40120-024-00674-x
Pierre Labauge, Alain Créange, Thibault Moreau, Jocelyne Nouvet-Gire, Bernard Pedespan, Olivier Heinzlef, Nathalie Texier, Marilyn Gros, Catherine Marti, Marta Ruiz, Mikel Martinez, Giovanni Castelnovo
Introduction: Treatment persistence and adherence are essential for achieving therapeutic goals in patients with multiple sclerosis (MS). OroSEP is an independent patient-support program (PSP) in France for patients with relapsing-remitting MS (RRMS) receiving oral disease-modifying therapies.
Methods: TEC-ADHERE (NCT04221191; 08/19/2019-09/15/2022) was a prospective, non-interventional, phase 4 study to assess the effect of OroSEP on persistence and adherence to dimethyl fumarate (DMF; Tecfidera™) in patients with RRMS. Outcomes were compared for patients in OroSEP versus non-OroSEP patients who received their neurologists' standard of care (SoC). Patients initiated DMF at month 0 (M0); follow-up visits occurred at M3 and M6. Primary outcome was persistence at M6. Secondary outcomes included persistence at M1 and M3, adherence at M6 (Girerd questionnaire), anxiety (Generalized Anxiety Disorder Assessment), patient satisfaction at M6 (Treatment Satisfaction Questionnaire for Medication), patient and neurologist satisfaction with OroSEP participation, and adverse events (AEs).
Results: Per-protocol population included 341 patients (OroSEP, n = 135; SoC, n = 206). Persistence was similar for OroSEP vs SoC (M6, 75.9% vs 76.6%; M1, 96.0% vs 92.4%; M3, 85.5% vs 89.0%). At M6, mean adherence was higher for OroSEP (5.4) vs SoC (4.7; p < 0.0001), and good adherence (Girerd score = 6) was achieved by more OroSEP patients (55.7%) than SoC patients (29.6%; p < 0.01). Mean anxiety scores were lower in the OroSEP group than in the SoC group at baseline (7.1 vs 8.8; p = 0.02) and M6 (3.4 vs 6.1; p < 0.001). Mean satisfaction scores at M6 were higher for OroSEP (77.4) vs SoC (64.2; p < 0.01). Most neurologists (n = 11/14) agreed that OroSEP helped improve adherence. Treatment-related AEs occurred in 62 (36.3%) OroSEP patients and 76 (42.9%) SoC patients; most common were flushing, diarrhea, hot flush, and abdominal pain.
Conclusion: These outcomes support the value of PSPs in encouraging adherence, alleviating anxiety, improving patient satisfaction, and supporting patients to be more independent in managing MS.
导言:坚持治疗是多发性硬化症(MS)患者实现治疗目标的关键。OroSEP是法国一项独立的患者支持计划(PSP),针对接受口服改变病情疗法的复发性缓解型多发性硬化症(RRMS)患者:TEC-ADHERE(NCT04221191;08/19/2019-09/15/2022)是一项前瞻性、非干预性的4期研究,旨在评估OroSEP对RRMS患者坚持和依从富马酸二甲酯(DMF;Tecfidera™)的影响。研究比较了OroSEP患者与非OroSEP患者接受神经科医生标准护理(SoC)的结果。患者在第0个月(M0)开始使用DMF;在M3和M6进行随访。主要结果是 M6 时的持续性。次要结果包括:M1和M3时的持续性、M6时的依从性(Girerd问卷)、焦虑(广泛性焦虑症评估)、M6时的患者满意度(药物治疗满意度问卷)、患者和神经科医生对参与OroSEP的满意度以及不良事件(AEs):按协议人群包括 341 名患者(OroSEP,135 人;SoC,206 人)。OroSEP与SoC的坚持率相似(M6,75.9% vs 76.6%;M1,96.0% vs 92.4%;M3,85.5% vs 89.0%)。在 M6 阶段,OroSEP 的平均依从性(5.4)高于 SoC(4.7;P 结论:这些结果支持了 PSP 的价值:这些结果支持了PSP在鼓励患者坚持治疗、减轻焦虑、提高患者满意度以及支持患者更独立地管理多发性硬化症方面的价值:试验注册:ClinicalTrials.gov 标识符,NCT04221191。
{"title":"TEC-ADHERE: Real-World Persistence and Adherence on Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis in the French OroSEP Patient-Support Program.","authors":"Pierre Labauge, Alain Créange, Thibault Moreau, Jocelyne Nouvet-Gire, Bernard Pedespan, Olivier Heinzlef, Nathalie Texier, Marilyn Gros, Catherine Marti, Marta Ruiz, Mikel Martinez, Giovanni Castelnovo","doi":"10.1007/s40120-024-00674-x","DOIUrl":"10.1007/s40120-024-00674-x","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment persistence and adherence are essential for achieving therapeutic goals in patients with multiple sclerosis (MS). OroSEP is an independent patient-support program (PSP) in France for patients with relapsing-remitting MS (RRMS) receiving oral disease-modifying therapies.</p><p><strong>Methods: </strong>TEC-ADHERE (NCT04221191; 08/19/2019-09/15/2022) was a prospective, non-interventional, phase 4 study to assess the effect of OroSEP on persistence and adherence to dimethyl fumarate (DMF; Tecfidera™) in patients with RRMS. Outcomes were compared for patients in OroSEP versus non-OroSEP patients who received their neurologists' standard of care (SoC). Patients initiated DMF at month 0 (M0); follow-up visits occurred at M3 and M6. Primary outcome was persistence at M6. Secondary outcomes included persistence at M1 and M3, adherence at M6 (Girerd questionnaire), anxiety (Generalized Anxiety Disorder Assessment), patient satisfaction at M6 (Treatment Satisfaction Questionnaire for Medication), patient and neurologist satisfaction with OroSEP participation, and adverse events (AEs).</p><p><strong>Results: </strong>Per-protocol population included 341 patients (OroSEP, n = 135; SoC, n = 206). Persistence was similar for OroSEP vs SoC (M6, 75.9% vs 76.6%; M1, 96.0% vs 92.4%; M3, 85.5% vs 89.0%). At M6, mean adherence was higher for OroSEP (5.4) vs SoC (4.7; p < 0.0001), and good adherence (Girerd score = 6) was achieved by more OroSEP patients (55.7%) than SoC patients (29.6%; p < 0.01). Mean anxiety scores were lower in the OroSEP group than in the SoC group at baseline (7.1 vs 8.8; p = 0.02) and M6 (3.4 vs 6.1; p < 0.001). Mean satisfaction scores at M6 were higher for OroSEP (77.4) vs SoC (64.2; p < 0.01). Most neurologists (n = 11/14) agreed that OroSEP helped improve adherence. Treatment-related AEs occurred in 62 (36.3%) OroSEP patients and 76 (42.9%) SoC patients; most common were flushing, diarrhea, hot flush, and abdominal pain.</p><p><strong>Conclusion: </strong>These outcomes support the value of PSPs in encouraging adherence, alleviating anxiety, improving patient satisfaction, and supporting patients to be more independent in managing MS.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04221191.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"177-192"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624959","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}
Pub Date : 2025-02-01Epub Date: 2024-11-26DOI: 10.1007/s40120-024-00685-8
Craig M McDonald, Jacob S Elkins, Sai Dharmarajan, Katherine Gooch, Teofil Ciobanu, Claire J Lansdall, Alexander P Murphy, Fiona McDougall, Eugenio M Mercuri, Ivana Audhya
Introduction: Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers' perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively).
Methods: In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers' impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses.
Results: MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90-2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30-1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase).
Conclusion: These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD.
{"title":"Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy.","authors":"Craig M McDonald, Jacob S Elkins, Sai Dharmarajan, Katherine Gooch, Teofil Ciobanu, Claire J Lansdall, Alexander P Murphy, Fiona McDougall, Eugenio M Mercuri, Ivana Audhya","doi":"10.1007/s40120-024-00685-8","DOIUrl":"10.1007/s40120-024-00685-8","url":null,"abstract":"<p><strong>Introduction: </strong>Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers' perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively).</p><p><strong>Methods: </strong>In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers' impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses.</p><p><strong>Results: </strong>MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90-2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30-1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase).</p><p><strong>Conclusion: </strong>These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov identifier, NCT05096221.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"211-225"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716669","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}
Pub Date : 2025-02-01Epub Date: 2024-12-21DOI: 10.1007/s40120-024-00691-w
Annette Janus, Daniël Dumas, Juliette Le Douce, Sébastien Marie, Giuseppe Pasculli, Pauline Bambury, Sighild Lemarchant, Philip Kremer, Yann Godfrin
Introduction: Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells. NX210c demonstrated a good safety profile in a single ascending dose phase 1a clinical study. The present multiple ascending dose phase 1b study was performed to evaluate the tolerability and pharmacological effects of repeated doses of NX210c in healthy elderly (age: > 55 years) volunteers.
Methods: This was a randomized, placebo-controlled, double-blind study (EudraCT No. 2022-002868-76), investigating safety/tolerability, pharmacokinetics, and pharmacodynamics (including blood and cerebrospinal fluid biomarkers). Participants received 5 or 10 mg/kg NX210c or placebo (10-min infusion) thrice weekly for 4 weeks in an ascending dose fashion. Follow-up was conducted 2 weeks after last dosing.
Results: The investigation included 29 participants. No serious adverse events were recorded and all adverse events were mild. Dedicated central nervous system testing did not reveal neurotoxicity. Biomarker evaluation showed a statistically significant reduction in blood claudin-5 and a trend toward reduction of blood homocysteine. In silico data modelling revealed salient pharmacokinetic-pharmacodynamic relationships, including reduction of claudin-5, neurofilament light chain, and SPARC-like protein 1 release, and degradation of homocysteine.
Conclusion: Multiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available.
{"title":"Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.","authors":"Annette Janus, Daniël Dumas, Juliette Le Douce, Sébastien Marie, Giuseppe Pasculli, Pauline Bambury, Sighild Lemarchant, Philip Kremer, Yann Godfrin","doi":"10.1007/s40120-024-00691-w","DOIUrl":"10.1007/s40120-024-00691-w","url":null,"abstract":"<p><strong>Introduction: </strong>Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells. NX210c demonstrated a good safety profile in a single ascending dose phase 1a clinical study. The present multiple ascending dose phase 1b study was performed to evaluate the tolerability and pharmacological effects of repeated doses of NX210c in healthy elderly (age: > 55 years) volunteers.</p><p><strong>Methods: </strong>This was a randomized, placebo-controlled, double-blind study (EudraCT No. 2022-002868-76), investigating safety/tolerability, pharmacokinetics, and pharmacodynamics (including blood and cerebrospinal fluid biomarkers). Participants received 5 or 10 mg/kg NX210c or placebo (10-min infusion) thrice weekly for 4 weeks in an ascending dose fashion. Follow-up was conducted 2 weeks after last dosing.</p><p><strong>Results: </strong>The investigation included 29 participants. No serious adverse events were recorded and all adverse events were mild. Dedicated central nervous system testing did not reveal neurotoxicity. Biomarker evaluation showed a statistically significant reduction in blood claudin-5 and a trend toward reduction of blood homocysteine. In silico data modelling revealed salient pharmacokinetic-pharmacodynamic relationships, including reduction of claudin-5, neurofilament light chain, and SPARC-like protein 1 release, and degradation of homocysteine.</p><p><strong>Conclusion: </strong>Multiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"357-377"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872565","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}
Pub Date : 2025-02-01Epub Date: 2024-12-04DOI: 10.1007/s40120-024-00687-6
Carlo Cattaneo, Javier Pagonabarraga
Sex differences in epidemiology, clinical features, and therapeutical responses are emerging in several movement disorders, even though they are still not widely recognized. Parkinson's disease (PD) is not an exception: men and women suffering from PD have different levels of disability. Research has been performed using multiple databases and scientific journals; this review summarizes the available evidence on sex differences in PD regarding epidemiology, risk factors, genetics, clinical phenotype, social impact, and therapeutic management. The role of hormones in determining such differences is also briefly discussed. The results confirm the existence of differences between men and women in PD; women have a higher risk of developing disabling motor complications and non-motor fluctuations compared to men, while men have a higher risk of developing cognitive impairment, postural instability, and gait disorders. Improving our knowledge in these differences may result in the implementation of strategies for disease-tailored treatment and management.
{"title":"Sex Differences in Parkinson's Disease: A Narrative Review.","authors":"Carlo Cattaneo, Javier Pagonabarraga","doi":"10.1007/s40120-024-00687-6","DOIUrl":"10.1007/s40120-024-00687-6","url":null,"abstract":"<p><p>Sex differences in epidemiology, clinical features, and therapeutical responses are emerging in several movement disorders, even though they are still not widely recognized. Parkinson's disease (PD) is not an exception: men and women suffering from PD have different levels of disability. Research has been performed using multiple databases and scientific journals; this review summarizes the available evidence on sex differences in PD regarding epidemiology, risk factors, genetics, clinical phenotype, social impact, and therapeutic management. The role of hormones in determining such differences is also briefly discussed. The results confirm the existence of differences between men and women in PD; women have a higher risk of developing disabling motor complications and non-motor fluctuations compared to men, while men have a higher risk of developing cognitive impairment, postural instability, and gait disorders. Improving our knowledge in these differences may result in the implementation of strategies for disease-tailored treatment and management.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"57-70"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770711","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}