Neurology and Therapy最新文献

{"title":"Comparative Evaluation of Rituximab Versus Approved Therapies in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Network Meta-analysis.","authors":"Mahdi Barzegar, Sara Samadzadeh, Bertrand Audoin, Achim Berthele, Ayse Altintas, Barbara Willekens, Sini Laakso, Shima Jahani, Viktoria Papp, Clarissa Zappe, Antonia Lefter, Aksel Siva, Alireza Afshari-Safavi, Sören Möller, Beatrijs Wokke, Rosa Cortese, Zsolt Illes, Saif Huda, Rommer Paulus, Silvia Messina, Nicolas Collongues, Marius Ringelstein, Álvaro Cobo-Calvo, Yael Hacohen, Georgina Arrambide, Jacqueline Palace, Sara Mariotto, Romain Marignier, Ruth Geraldes, Friedemann Paul, Nasrin Asgari","doi":"10.1007/s40120-026-00989-x","DOIUrl":"10.1007/s40120-026-00989-x","url":null,"abstract":"<p><strong>Introduction: </strong>Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuro-autoimmune disease. Monoclonal antibodies targeting B cell antigens CD19 and CD20, the interleukin-6 receptor, or the complement cascade are used as preventive therapies to reduce relapse rates. We conducted a network meta-analysis (NMA) to compare the effect of rituximab on time to first relapse with ravulizumab, eculizumab, inebilizumab, and satralizumab in patients with NMOSD who are aquaporin-4 (AQP4)-IgG-positive.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed, Scopus, CINAHL, EMBASE, Web of Science, the Cochrane Library, and gray literature sources up to October 31, 2024, and updated on November 1, 2025, following PRISMA guidelines. A network meta-analysis of randomized and open-label trials was conducted to compare time to first relapse between rituximab and other monoclonal antibody therapies.</p><p><strong>Results: </strong>From 6337 records, 3825 duplicates were removed; 2512 were screened, 2327 excluded, leaving eight trials. The prior treatment, relapse history, and definitions and adjudication of relapse varied across studies. Rituximab showed higher hazard ratio (HR) point estimates for time to first relapse compared with ravulizumab with or without immunosuppressive therapies (IST) (HR 5.00, 95% CI 0.25, 101.01) and eculizumab ± IST (HR 1.17, 95% CI 0.12, 10.89), but were lower compared with satralizumab ± IST (HR 0.29, 95% CI 0.04, 2.23). In patients not receiving IST, rituximab showed numerically higher HR compared with ravulizumab (HR 3.33, 95% CI 0.13, 83.16) and eculizumab (HR 1.59, 95% CI 0.05, 50.17), but lower point estimates compared with inebilizumab (HR 0.31, 95% CI 0.04, 2.31) and satralizumab (HR 0.27, 95% CI 0.03, 2.21).</p><p><strong>Conclusion: </strong>This NMA showed hazard ratio point estimates favoring eculizumab and ravulizumab over rituximab. However, wide, overlapping confidence intervals and between-study heterogeneity indicate substantial uncertainty. Head-to-head trials or registry-based studies are needed to determine the most effective treatment for AQP4-IgG-positive NMOSD.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2449-2465"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456293","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 Caregivers' Experiences of Rett Syndrome: A Multinational Study of Symptoms and Meaningful Outcomes of Potential Treatments.","authors":"Bruria Ben-Zeev, Elsa Rossignol, Daniel E Lumsden, Natalie Guido-Estrada, Deborah A Bilder, Monica Coenraads, Sigal Hertz Tirosh, Paige Nues, Sabrina Millson, Rachael Stevenson, John Ashkenas, Chelsea Karbocus, Emily McGinnis, Kristin LaBounty Phillips","doi":"10.1007/s40120-026-01003-0","DOIUrl":"10.1007/s40120-026-01003-0","url":null,"abstract":"<p><strong>Introduction: </strong>Caregivers have first-hand experience of facing the daily challenges of Rett syndrome (RTT). The aim of this study was to understand caregivers' experiences of RTT, including challenging symptoms that caregivers hope novel therapies will address.</p><p><strong>Methods: </strong>This non-interventional, qualitative and quantitative market research study engaged caregivers of individuals with RTT in the USA, the UK, Canada, and Israel, through an online survey comprising both closed- and open-ended items. Survey domains included age of symptom onset, symptom severity and impact on quality of life, the most challenging symptoms, and caregiver perspectives on meaningful improvement.</p><p><strong>Results: </strong>A total of 323 caregivers completed the survey. Symptoms with the most severe and lasting impact on patients' quality of life typically presented by 6 years of age. These symptoms included loss of speech, loss of purposeful use of hands, and gait disturbances. Caregivers reported a dynamic and lifelong burden associated with impairments in activities of daily living and expressed a desire for improvement across these functional domains following gene therapy treatment.</p><p><strong>Conclusion: </strong>Despite RTT's clinical heterogeneity, similarities emerged in caregivers' daily experiences and their hopes regarding gene therapy treatment. Caregivers believe meaningful improvements for people with RTT would be improved function and enhanced autonomy related to fine and gross motor abilities, and improved ability to communicate needs.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2567-2582"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697578","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":"Harnessing Brain Age-Specific Effects on the Associations Between Sleep Quality, Glymphatic Function, and Cognition in Normal Ageing Adults: Insights for Gerotherapeutics.","authors":"Hanna Lu, Zeyan Li, Liwei Guo, Xi Ni, Ben Chen, Xiaomei Zhong, Yanling Zhou, Yuping Ning","doi":"10.1007/s40120-026-00999-9","DOIUrl":"10.1007/s40120-026-00999-9","url":null,"abstract":"<p><strong>Introduction: </strong>The interplay between glymphatic function and sleep quality is crucial for brain health and cognitive longevity in late adulthood. Beyond chronological age, whether brain age has specific effects on the associations between glymphatic function, sleep quality, and cognition are understudied in cognitive unimpaired adults.</p><p><strong>Methods: </strong>Structural and diffusion magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 582, age range 18-87 years) were used to calculate brain age metrics and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. Brain age metrics comprised estimated brain age and the brain predicted age difference (brain-PAD). Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Cognitive assessments included accuracy, reaction time, intraindividual variability of reaction time, and fluid intelligence.</p><p><strong>Results: </strong>Leftward asymmetry of the DTI-ALPS index was consistently observed across brain age-specific groups. The brain-PAD score was significantly correlated with a lower left DTI-ALPS index. Adults with a positive brain-PAD score exhibited a robust correlation between DTI-ALPS indices and sleep quality features, whereas those with a negative brain-PAD score showed a reliable correlation between DTI-ALPS indices and cognition. Mediation analyses further revealed that the relationship between left DTI-ALPS index and sleep efficiency was mediated by brain age.</p><p><strong>Conclusion: </strong>This study provides the first demonstration that lateral differences in the DTI-ALPS index vary according to brain ageing statuses. The two distinct profiles of the sleep-glymphatic function-cognition connections observed in relation to brain-PAD scores suggest that a preserved brain age may serve as a protective factor against age-related decline in glymphatic function. These findings may underscore the translational potential of brain age models as both clinical biomarkers and modifiable targets for interventions aimed at promoting healthy longevity and brain resilience.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2583-2602"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631010","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":"Exploring the Role of Early Add-On Cenobamate in Uncontrolled Focal Epilepsy: A Critical Appraisal of the Evidence.","authors":"Simona Lattanzi, Giancarlo Di Gennaro, Carlo Andrea Galimberti, Alfonso Iudice, Carlo Di Bonaventura","doi":"10.1007/s40120-026-00997-x","DOIUrl":"10.1007/s40120-026-00997-x","url":null,"abstract":"<p><strong>Introduction: </strong>Cenobamate is a third-generation antiseizure medication (ASM) for the treatment of uncontrolled focal seizures. As evidence accumulated across randomized clinical trials and real-world studies, clinically relevant questions have emerged regarding its comparative efficacy, optimal timing of introduction, safety and interaction profile, long-term retention, and outcomes beyond seizure control.</p><p><strong>Methods: </strong>This structured expert narrative review addressed four predefined domains-efficacy, safety and retention, pharmacological interactions, and patient-centered outcomes-using PICO-formulated questions. PubMed searches identified randomized controlled trials, network meta-analyses, and observational studies of adjunctive cenobamate in adults with focal epilepsy. Given heterogeneity in design and reporting, evidence was synthesized narratively and interpreted through multidisciplinary expert discussion.</p><p><strong>Results: </strong>Across diverse study types, cenobamate consistently demonstrated high efficacy, including clinically relevant rates of seizure freedom and ≥ 50% response. Several real-world analyses suggested that earlier introduction-typically after failure of two prior ASMs-may be associated with higher seizure-freedom rates than early use of other ASMs; these signals derived from non-randomized comparisons and may reflect residual confounding. Safety was dominated by predictable, dose-related central nervous system events, with tolerability strongly dependent on titration and proactive adjustment of interacting ASMs (notably clobazam, phenytoin, phenobarbital, and high-dose sodium-channel blockers). Long-term retention remained high across cohorts. Cognitive performance was generally stable and psychiatric symptoms stable or improved, with quality-of-life gains reported, including in patients who had previously failed resective surgery or neuromodulation, albeit from uncontrolled data.</p><p><strong>Conclusions: </strong>Cenobamate may offer substantial benefit in adults with uncontrolled focal epilepsy, with a favorable efficacy-tolerability balance, high retention, and possible advantages when introduced earlier (after two ASMs). Its interaction profile underscores the importance of careful management of concomitant ASMs. Because the comparative signals derive largely from non-randomized data, prospective controlled research is needed to confirm any benefit of early use and to better characterize long-term cognitive and psychiatric effects.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2393-2415"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422843","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":"A Practical Guide to Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy.","authors":"Johannes Jakobsen, Chafic Karam, Krista Kuitwaard, Todd Levine","doi":"10.1007/s40120-026-00981-5","DOIUrl":"10.1007/s40120-026-00981-5","url":null,"abstract":"<p><p>Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common immune-mediated demyelinating peripheral neuropathy. CIDP is characterized by progressive muscle weakness, areflexia, and often sensory loss. The etiology is not well understood, but autoimmune pathophysiology is evident, and immunomodulatory treatments such as intravenous immunoglobulin, corticosteroids, and plasma exchange are commonly used. The 2021 revision of the international CIDP guideline by the European Academy of Neurology and Peripheral Nerve Society offers recommendations on CIDP diagnosis and treatment; however, local guidelines and protocols can provide additional insights into CIDP management in clinical practice. In this article, a group of EU and US physicians with experience in CIDP management aims to provide insights into CIDP treatment considerations using regional resources and professional experience. Owing to the heterogeneity of the disease and its variable clinical course, CIDP treatment response varies among patients. It is therefore important to consider not only regional pressures, such as immunoglobulin availability, which may limit its use, but also how to monitor treatment response and make informed decisions about when to adjust, withdraw, or switch treatment for the patient's benefit. As misdiagnosis of CIDP is common, diagnosis should be reconsidered in cases where there is a lack of treatment response. Using example cases, this article draws on regional treatment frameworks and the expert experience of EU and US professionals to provide a resource for trainee physicians and professionals involved in the management of CIDP.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2359-2375"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422838","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":"Disease-Modifying Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: Current Status and Future Perspectives.","authors":"Toshihiro Ide, Masaaki Yoshikawa, Haruki Koike","doi":"10.1007/s40120-026-00994-0","DOIUrl":"10.1007/s40120-026-00994-0","url":null,"abstract":"<p><p>Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder caused by pathogenic variants in the transthyretin (TTR) gene resulting in progressive sensorimotor neuropathy, autonomic dysfunction, and effects on other organs, particularly the heart. Historically, treatment options have been limited to liver transplantation and symptomatic management, and the disease was associated with poor prognosis and progressive disability. However, over the past decade, the therapeutic landscape has been transformed by the development of disease-modifying therapies that target the underlying pathophysiology of TTR amyloid formation. These therapies include TTR stabilizers, such as tafamidis, diflunisal, and acoramidis, as well as RNA-silencing agents, such as patisiran, vutrisiran, inotersen, and eplontersen, which reduce hepatic production of TTR and slow disease progression. Clinical trials of RNA interference therapies have demonstrated significant improvements in neuropathy impairment scores, quality of life, and functional outcomes, with acceptable safety profiles and sustained long-term benefits. Emerging gene-editing approaches, including CRISPR-based therapies like NTLA-2001, may provide a one-time treatment and long-term disease control, representing a promising future direction for managing ATTRv-PN. Despite these advances, important challenges remain. These include high treatment costs, limited global accessibility, uncertainty regarding optimal treatment selection and sequencing, and the need for long-term real-world, patient-centered outcome data. This review summarizes current disease-modifying therapies for ATTRv-PN, compares their mechanisms and clinical evidence, and discusses unmet needs and future research directions, with the aim of providing a practical and comprehensive overview for clinicians treating patients with ATTRv-PN.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2341-2358"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456223","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 Patient Experience of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Post-Diagnosis: Results from an International Survey.","authors":"Jonathan D Santoro, Gabrielle deFiebre, Julia Lefelar, Panayotes Demakakos, Danielle Hartigh, Magali Periquet, Khaleda Ahmadyar, Zara Morrison, Jacqueline Palace","doi":"10.1007/s40120-026-01010-1","DOIUrl":"10.1007/s40120-026-01010-1","url":null,"abstract":"<p><strong>Introduction: </strong>Data on the post-diagnosis experience of individuals with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and their caregivers are limited. We explored post-diagnosis treatment experience and satisfaction with care in individuals with MOGAD and associated caregiver burden.</p><p><strong>Methods: </strong>An online 57-question survey was distributed internationally to adults (aged ≥ 16 years) or caregivers assisting an adult or answering on behalf of a child (aged < 16 years) from October to December 2024.</p><p><strong>Results: </strong>Overall, 261 responses were collected (adults, 219; children, 42) across 27 countries. Of those prescribed a preventative treatment, 43% of adults (n = 71/167) and 42% of children (n = 13/31) stopped treatment; common reasons were side effects and lack of efficacy. Most adults (73%) and children (64%) reported difficulties accessing/trying to access MOGAD treatment and care. Substantial dissatisfaction was reported for chronic symptom management for adults (35%) and psychological/emotional support for children (31%). Compared with individuals with MOGAD (N = 261), caregivers (of adults, n = 61; of children, n = 42) were significantly more likely to report mental health impacts (26% vs 92%, respectively; p < 0.001).</p><p><strong>Conclusion: </strong>Persistent unmet care and support needs exist for individuals with MOGAD. Treatments were often stopped/changed, highlighting the need for more efficacious, tolerable, and approved therapies. Caregivers experience significant mental health impacts; improved support is needed.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2491-2508"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865164","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":"Real-World Response and Super-Response to Eptinezumab over 48 Weeks in Migraine: The Prospective Multicenter EMBRACE III Study.","authors":"Piero Barbanti, Cinzia Aurilia, Massimo Filippi, Alberto Doretti, Florindo d'Onofrio, Paola Scatena, Rosario Vecchio, Roberta Messina, Luisa Vinciguerra, Angelo Ranieri, Francesco Baldisseri, Paola Torelli, Marco Russo, Carolina Cutrona, Giovanna Viticchi, Gabriella Egeo, Massimo Autunno, Francesca Pistoia, Cinzia Finocchi, Cecilia Camarda, Stefano Messina, Steno Rinalduzzi, Valeria Drago, Luigi Caputi, Monica Bandettini di Poggio, Simone Quintana, Antonio Salerno, Marco Bartolini, Giulia Fiorentini, Jesuely Spieckert de Souza, Fabrizio Di Stani, Stefano Bonassi, Annamaria Porreca","doi":"10.1007/s40120-026-00971-7","DOIUrl":"10.1007/s40120-026-00971-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Long-term (&gt; 24 weeks) real-world evidence of eptinezumab's effectiveness is limited. We evaluated ≥ 50% and ≥ 75% response rates over 48 weeks in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EMBRACEIII (NCT05570149) is a prospective, multicenter, observational study. Adults with HFEM or CM who experienced ≥ 3 preventive treatment failures received eptinezumab 100 mg intravenously every 12 weeks, with optional 300 mg escalation after week 12 for inadequate response. Co-primary endpoints were ≥ 50% and ≥ 75% reductions in monthly migraine/headache days (MMD/MHD) at weeks 45-48 versus baseline. Secondary endpoints were changes in MMD/MHD, monthly analgesic intake (MAI), pain intensity (assessed using the numeric rating scale [NRS]), migraine-related disability and impact (assessed using the Headache Impact Test-6 [HIT-6], Migraine Disability Assessment [MIDAS], the Migraine Interictal Burden Scale-4 [MIBS-4]), patient-reported global treatment response (assessed using the Patient Global Impression of Change [PGI-C] questionnaire), and 100% response. Exploratory analyses assessed dose escalation, prior anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) treatment failures, responders without adverse events, ≥ 30% reduction in the NRS during residual attacks, and clinically complex subgroups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 261 patients (safety population) included in the study, 124 completed ≥ 48 weeks of treatment with eptinezumab. At week 48, the response rates for ≥ 50%, ≥ 75%, and 100% were 82.3%, 51.6%, and 9.7%, respectively. All secondary endpoints improved significantly (p &lt; 0.001), with significant reductions from baseline: MMD/MHD, - 15.5; MAI, - 14.9; NRS, - 3.3; HIT-6, -  20.6; MIDAS, - 74; and MIBS-4, - 4.3. Also, 94.8% of patients reported PGI-C improvement. Dose escalation occurred in 69.4% of patients. Patients receiving ≥ 3 doses of 300 mg eptinezumab achieved outcomes comparable to responders receiving 100 mg. Among patients with prior anti-CGRP mAb treatment failures (51.6%), ≥ 50% and 100% responders were similar to mAb-naïve patients, whereas ≥ 75% response was lower (37.5%; p = 0.002). Response rates of ≥ 50%,  ≥ 75% and 100% were achieved by 81.2%, 50.4%, and 8.5%, respectively, in patients without adverse events; 85.7%, 51.4%, and 8.6% in patients with psychiatric comorbidities; 87.8%, 54.9%, and 7.3% in patients with CM with medication overuse; and 89.2%, 50.0%, and 7.1% in patients with CM with both conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Eptinezumab demonstrated sustained 48-week effectiveness, with high response rates of ≥ 75% and 100% in a difficult-to-treat population. Effectiveness was preserved in patients with prior anti-CGRP mAb failures after 300 mg escalation and in clinically complex subgroups. Many patients achieved ≥ 30% reduction in NRS during residual migraine attacks.&lt;/p&gt;&lt;","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2779-2798"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205048","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":"Inhaled Levodopa for the Management of OFF Episodes in Patients with Parkinson's Disease: A Network Meta-analysis.","authors":"Omar Madani, Chetan Mistry, Rushab Shah, Grace Chattey, Leandro Guerra Primo, Hanne C Gadeberg, Stefano Perni, Ubong Silas, Carmen Walter, Georg-Alexander Pietsch, Günter Höglinger","doi":"10.1007/s40120-026-00991-3","DOIUrl":"10.1007/s40120-026-00991-3","url":null,"abstract":"<p><strong>Introduction: </strong>In the course of their disease, most patients with Parkinson's disease (PD) will experience OFF episodes, during which symptoms worsen despite symptomatic treatment. Current on-demand treatments for OFF episodes include inhaled levodopa and subcutaneous and sublingual apomorphine, however no head-to-head comparison of these treatments is available. We performed a network meta-analysis (NMA) to provide robust comparative evidence for on-demand OFF episode treatments.</p><p><strong>Methods: </strong>Randomized controlled trials assessing OFF episode treatments in patients with PD were identified in a systematic literature review. A feasibility assessment was conducted considering OFF time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, Patient Global Impression of Change score (PGI-C), and safety outcomes. An NMA was carried out using a random effects model.</p><p><strong>Results: </strong>Twenty-one trials were identified in the systematic literature review, 11 of which were included in the feasibility assessment and deemed suitable to be included in the NMA. No statistically significant difference in OFF time was observed between patients receiving inhaled levodopa and those receiving subcutaneous apomorphine, and no statistically significant difference in UPDRS Part III scores or probability of PGI-C score improvements, all-cause discontinuation, or adverse events (AEs) were observed between patients receiving inhaled levodopa, subcutaneous apomorphine, or sublingual apomorphine. Subcutaneous apomorphine had significantly higher probability of treatment discontinuation due to adverse events compared to inhaled levodopa (Log odds ratio 20.712; 95% credible interval 1.855, 55.991).</p><p><strong>Conclusion: </strong>Inhaled levodopa demonstrated no statistically significant difference in efficacy with subcutaneous or sublingual apomorphine, however inhaled levodopa had a lower probability of treatment discontinuation due to AEs than subcutaneous apomorphine. These data highlight that inhaled levodopa is a suitable non-invasive and well-tolerated treatment for OFF episodes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2689-2705"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397394","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 Effectiveness of Inebilizumab in Patients with Neuromyelitis Optica Spectrum Disorder: Interim Analysis of a Post-marketing Surveillance in Japan.","authors":"Kazuo Fujihara, Shinya Hirota, Muneyoshi Kudo, Hideaki Hida, Satoshi Yuki, Takashi Narisawa, Kyoko Kato","doi":"10.1007/s40120-026-01008-9","DOIUrl":"10.1007/s40120-026-01008-9","url":null,"abstract":"<p><strong>Introduction: </strong>Inebilizumab is used in Japan for relapse prevention in aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Nationwide post-marketing surveillance (PMS) is underway to evaluate the real-world safety and effectiveness of inebilizumab in Japanese patients with NMOSD.</p><p><strong>Methods: </strong>This PMS interim analysis assessed safety and effectiveness of inebilizumab in Japanese patients with NMOSD initiating treatment between June 2021 and November 2023, using data through June 2025.</p><p><strong>Results: </strong>The safety analysis set included 228 patients, and the effectiveness analysis set included 224 patients after excluding three patients from N-MOmentum (NCT02200770) and one without confirmed anti-AQP4 antibody positivity. Twenty-one (safety analysis set) and 20 (effectiveness analysis set) patients discontinued treatment. In the safety analysis set, 194 patients (85.1%) were female, and the mean ± standard deviation (SD) age was 54.2 ± 13.1 years. Adverse drug reactions (ADRs) occurred in 74 patients (32.5%); 31 (13.6%) were serious. Common ADRs were infections (14.5%, n = 33); serious infections (5.7%, n = 13) included COVID-19 (1.3%, n = 3), COVID-19 pneumonia (0.9%, n = 2), and urinary tract infection (0.9%, n = 2). Two fatal ADRs (interstitial lung disease, sudden cardiac death) occurred, for which a causal relationship with inebilizumab could not be excluded. In the effectiveness analysis set, the annualized relapse rate (95% CI) decreased from 0.40 (0.33-0.47) per person-year during the 2 years before inebilizumab initiation to 0.10 (0.07-0.14) per person-year after inebilizumab initiation. From baseline to 1 year, the proportion of patients receiving neither concomitant oral glucocorticoids nor immunosuppressants increased from 5.4% to 33.0%, and the mean ± SD oral glucocorticoid dose decreased from 11.7 ± 7.9 mg/day to 4.3 ± 4.7 mg/day.</p><p><strong>Conclusion: </strong>In this interim analysis, the safety profile of inebilizumab was consistent with prior evidence and no new safety concerns were identified. Inebilizumab reduced relapse rates and decreased concomitant use of oral glucocorticoids and immunosuppressants in patients with NMOSD.</p><p><strong>Umin clinical trials registry: </strong>UMIN000044431.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2509-2526"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851409","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}