Therapeutic Advances in Neurological Disorders最新文献

{"title":"Clinical and device-based predictors of improved experience of activities of daily living after a multidisciplinary inpatient treatment for people with Parkinson's disease: a cohort study.","authors":"Judith Oppermann, Vera Tschentscher, Julius Welzel, Johanna Geritz, Clint Hansen, Ralf Gold, Walter Maetzler, Raphael Scherbaum, Lars Tönges","doi":"10.1177/17562864241277157","DOIUrl":"https://doi.org/10.1177/17562864241277157","url":null,"abstract":"<p><strong>Background: </strong>The inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is an important therapeutical approach to improving gait and activities of daily living (ADL) of people with PD (PwP). Wearable device-based parameters (DBP) are new options for specific gait analyses toward individualized treatments.</p><p><strong>Objectives: </strong>We sought to identify predictors of perceived ADL benefit taking clinical scores and DBP into account. Additionally, we analyzed DBP and clinical scores before and after PD-MCT.</p><p><strong>Design: </strong>Exploratory observational cohort study.</p><p><strong>Methods: </strong>Clinical scores and DBP of 56 PwP (mean age: 66.3 years, median Hoehn and Yahr (H&Y) stage: 2.5) were examined at the start and the end of a 14-day inpatient PD-MCT in a German University Medical Center. Participants performed four straight walking tasks under single- and dual-task conditions for gait analyses. Additionally, clinical scores of motor and nonmotor functions and quality of life (QoL) were assessed. Using dichotomized data of change in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part II (MDS-UPDRS II) as a dependent variable and clinical and DBP as independent variables, a binomial logistic regression model was implemented.</p><p><strong>Results: </strong>Young age, high perceived ADL impairment at baseline, high dexterity skills, and a steady gait were significant predictors of ADL benefit after PD-MCT. DBP like gait speed, number of steps, step time, stance time, and double limb support time were improved after PD-MCT. In addition, motor functions (e.g., MDS-UPDRS III and IV), QoL, perceived ADL (MDS-UPDRS II), and experience of nonmotor functions (MDS-UPDRS I) improved significantly.</p><p><strong>Conclusion: </strong>The logistic regression model identified a group of PwP who had the most probable perceived ADL benefit after PD-MCT. Additionally, gait improved toward a faster and more dynamic gait. Using wearable technology in context of PD-MCT is promising to offer more personalized therapeutical concepts.</p><p><strong>Trial registration: </strong>German Clinical Trial Register, https://drks.de; DRKS00020948 number, 30 March 2020, retrospectively registered.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241277157"},"PeriodicalIF":4.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 association of disease-modifying therapies for multiple sclerosis and BTK inhibitors with epilepsy.","authors":"Afsaneh Shirani, Nil Saez-Calveras, Jack P Antel, Moein Yaqubi, Wayne Moore, Amy L Brewster, Olaf Stuve","doi":"10.1177/17562864241276204","DOIUrl":"10.1177/17562864241276204","url":null,"abstract":"<p><strong>Background: </strong>Multiple lines of evidence suggest a role of inflammation in epilepsy. Seizure incidence in patients with multiple sclerosis (MS) is twofold to threefold higher than the age-matched general population.</p><p><strong>Objectives: </strong>To explore the association of MS disease-modifying therapies (DMTs) and FDA-approved Bruton tyrosine kinase inhibitors (for lymphocytic malignancies) with the occurrence of epilepsy using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Design: </strong>Secondary analysis of the FAERS database.</p><p><strong>Methods: </strong>We conducted a disproportionality analysis of FAERS between 2003-Q4 and 2023-Q3. MS DMTs and the Bruton tyrosine kinase inhibitor, ibrutinib, were included in the analysis. An inverse association was defined by a 95% confidence interval (CI) upper limit of reporting odds ratio (ROR) <1.</p><p><strong>Results: </strong>We found an inverse association of ibrutinib, ocrelizumab, ofatumumab, rituximab, and teriflunomide with epilepsy. The strongest inverse association was seen with ibrutinib (ROR: 0.338; 95% CI: 0.218-0.524).</p><p><strong>Conclusion: </strong>Our findings suggest the possibility of considering these medications for repurposing opportunities in epilepsy and support a potential pathogenic role of leukocyte subsets in seizure perpetuation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241276204"},"PeriodicalIF":4.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintenance of zilucoplan efficacy in patients with generalised myasthenia gravis up to 24 weeks: a model-informed analysis.","authors":"Guillemette de la Borderie, Damien Chimits, Babak Boroojerdi, Melissa Brock, Petra W Duda, Fiona Grimson, Paul Mahoney, Foteini Strimenopoulou, Gary Cutter, Inmaculada Aban, Susanna Brauner, Malin Petersson, James F Howard, Nathan Bennett","doi":"10.1177/17562864241279125","DOIUrl":"10.1177/17562864241279125","url":null,"abstract":"<p><strong>Background: </strong>Clinical efficacy of zilucoplan has been demonstrated in a 12-week, placebo-controlled, phase III study in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG). However, placebo-controlled zilucoplan data past 12 weeks are not available.</p><p><strong>Objectives: </strong>Predict the treatment effect of zilucoplan versus control (placebo or standard of care) in patients with gMG up to 24 weeks.</p><p><strong>Design: </strong>A model-informed analysis (MIA) within a Bayesian framework.</p><p><strong>Methods: </strong>Part 1 of the MIA comprised a control meta-regression using aggregate data on control response over time from randomised studies and a national myasthenia gravis (MG) registry. In Part 2, a combined Bayesian analysis of individual patient-level data from the phase II (NCT03315130), RAISE (NCT04115293) and RAISE-XT (NCT04225871) studies of zilucoplan was conducted using posterior distributions from Part 1 as informative priors. Population mean treatment effect in the change from baseline (CFB) at week 24 in MG-Activities of Daily Living (MG-ADL) and quantitative MG (QMG) scores for zilucoplan versus control were assessed.</p><p><strong>Results: </strong>At week 24, the predicted mean CFB in MG-ADL score was -4.55 (95% credible interval: -6.04, -3.13) with zilucoplan versus -2.00 (-3.35, -0.64) with control (difference: -2.55 [-3.76, -1.40]). The probability of a favourable treatment effect as measured by MG-ADL score at week 24 with zilucoplan versus control was >99.9%. There was an 82.8% probability that the difference in the predicted mean CFB in MG-ADL score at week 24 was greater than the clinically meaningful threshold (⩾2.0-point improvement). Comparable results were observed with QMG.</p><p><strong>Conclusion: </strong>This MIA demonstrates the maintenance of efficacy with zilucoplan versus control up to 24 weeks. Through combining real-world evidence with data from randomised studies, this novel method to estimate long-term treatment efficacy facilitated reduced exposure to placebo in the phase III RAISE study. This methodology could be used to reduce the length of future placebo-controlled studies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241279125"},"PeriodicalIF":4.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside.","authors":"Eliana Ege, Daniel Briggi, Peter Vu, Jianguo Cheng, Feng Lin, Jijun Xu","doi":"10.1177/17562864241252718","DOIUrl":"https://doi.org/10.1177/17562864241252718","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design: Review. A thorough literature search was conducted using the terms 'dorsal root ganglion' and 'chemotherapy-induced peripheral neuropathy', along with appropriate variations. Searched databases included PubMed, EMBASE, Medline, Cochrane Library, Wiley Library, and Web of Science. Inclusion criteria targeted all English language, peer-reviewed original research from the inception of these databases to the present year. Review articles, book chapters, and other nonoriginal publications were excluded. Of 134 relevant studies identified, the majority were preclinical studies elucidating how various chemotherapeutic agents, especially taxanes, disrupt neurotransmission, inflammatory processes, and apoptotic pathways within sensory neurons of DRG. Not only do these effects correlate with the presentation of CIPN, but their disruption has also been shown to reduce CIPN symptoms in preclinical models. However, clinical studies addressing DRG interventions are very limited in number and scope at this time. These results reveal various pathways within DRG that may be effective targets for CIPN treatment. While limited, clinical studies do offer promise in the utility of DRG neuromodulation in managing painful CIPN. In the future, clinical trials are needed to assess interventions aimed at these neuronal and nonneuronal pathological targets to better treat this complex condition.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241252718"},"PeriodicalIF":4.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CYP2C19</i> genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of trough lacosamide concentration or clinical response.","authors":"Yue Li, Hong-Li Guo, Jie Wang, Yuan-Yuan Zhang, Wei-Jun Wang, Jian Huang, Lin Fan, Ya-Hui Hu, Xiao-Peng Lu, Feng Chen","doi":"10.1177/17562864241273087","DOIUrl":"10.1177/17562864241273087","url":null,"abstract":"<p><strong>Background: </strong>The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug-drug interactions (DDIs), exert their influence on pediatric patients with epilepsy.</p><p><strong>Objectives: </strong>To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response.</p><p><strong>Design: </strong>Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children's Hospital of Nanjing Medical University were included in the analysis.</p><p><strong>Methods: </strong>The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose (<i>C</i> ₀/D) ratio and efficacy outcomes were compared.</p><p><strong>Results: </strong>Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the <i>CYP2C19</i> *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05-3.15; <i>p</i> = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying <i>CYP2C19</i> *2 or *3. Of note, the <i>C</i> ₀/D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the <i>C</i> ₀/D ratio when patients were concomitant with sodium channel blockers (SCBs).</p><p><strong>Conclusion: </strong>This study was the first to confirm that <i>CYP2C19</i> *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241273087"},"PeriodicalIF":4.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary results on temporal evolution and clinical implications of atherosclerotic plaque in branch atheromatous disease after statin treatment.","authors":"Yen-Chu Huang, Yuan-Hsiung Tsai, Leng-Chieh Lin, Hsu-Huei Weng, Jiann-Der Lee, Jen-Tsung Yang","doi":"10.1177/17562864241273902","DOIUrl":"10.1177/17562864241273902","url":null,"abstract":"<p><strong>Background: </strong>Branch atheromatous disease (BAD) is a primary cause of early neurological deterioration (END) in penetrating artery occlusion, leading to poor functional outcomes. While it has been proposed to classify BAD under large artery atherosclerosis, uncertainty exists regarding the optimal treatment strategy, including cholesterol-lowering targets.</p><p><strong>Objectives: </strong>We aimed to assess the clinical implications and temporal changes of atherosclerotic plaques before and after high-intensity statin treatment.</p><p><strong>Design: </strong>This is a high-resolution vessel-wall imaging sub-analysis of the trial of Statin and Dual Antiplatelet Therapy in Preventing Early Neurological Deterioration in Branch Atheromatous Disease (SATBRAD).</p><p><strong>Methods: </strong>In this prospective, single-group cohort study, participants in the treatment arm of the SATBRAD trial received early dual antiplatelet therapy and high-intensity statin treatment. The majority of these participants subsequently underwent high-resolution vessel-wall magnetic resonance imaging (MRI). Those with atheromatous plaques in the parent artery continued high-intensity statin treatment for 6 months, followed by a repeat MRI to monitor plaque changes.</p><p><strong>Results: </strong>There were 57 patients who underwent vessel-wall imaging and 24 exhibited contrast-enhanced plaques. Patients with contrast-enhanced plaques showed higher rates of END (29.2% vs 6.1%, <i>p</i> = 0.027), perfusion defects (62.5% vs 24.2%, <i>p</i> = 0.004), and lower rates of good outcomes at 3 months (50.0% vs 81.8%, <i>p</i> = 0.011). After adjusting for confounding factors, contrast-enhanced plaque had a negative impact on achieving a good outcome at 3 months (adjusted odds ratio = 0.04; 95% confidence interval = <0.01-0.60). Following high-intensity statin treatment in 36 patients, there was a notable reduction in stenosis (33.7% vs 29.3%, <i>p</i> = 0.005) and contrast-enhanced plaque volume (16.3 vs 11.6 mm³, <i>p</i> = 0.015).</p><p><strong>Conclusion: </strong>The study highlighted the association between contrast-enhanced atherosclerotic plaques, END, and poor functional outcomes, with high-intensity treatment leading to plaque volume reduction. These results underscore the shared pathology between BAD and intracranial atherosclerosis, emphasizing the necessity for further research and tailored treatment strategies for BAD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov; Identifier: NCT04824911 (https://clinicaltrials.gov/study/NCT04824911).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241273902"},"PeriodicalIF":4.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author response to Comment on: Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database.","authors":"Afsaneh Shirani, Anne H Cross, Olaf Stuve","doi":"10.1177/17562864241276848","DOIUrl":"10.1177/17562864241276848","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241276848"},"PeriodicalIF":4.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemorrhagic complications after stroke treatment with intravenous thrombolysis despite use of direct oral anticoagulants: an observational study.","authors":"Antonia Kleeberg,Peter A Ringleb,Ioana Huber,Jessica Jesser,Markus Möhlenbruch,Jan C Purrucker","doi":"10.1177/17562864241276206","DOIUrl":"https://doi.org/10.1177/17562864241276206","url":null,"abstract":"BackgroundFor patients experiencing ischemic stroke despite receiving therapy with direct oral anticoagulants (DOAC) and without endovascular treatment options, therapeutic prospects are currently dismal. Current guidelines recommend intravenous thrombolysis (IVT) only for patients who have received DOAC in very restricted settings, as an increased risk of bleeding is suspected. However, recent retrospective observational studies suggest that IVT is safe despite DOAC pretreatment.ObjectivesTo provide further evidence that IVT despite previous DOAC treatment is not associated with an increased risk of bleeding.DesignObservational retrospective study.MethodsDemographic, clinical, and radiological data of patients who received IVT (+/- endovascular thrombectomy) despite DOAC pretreatment between June 2021 and January 2024 were analyzed using descriptive statistics, including DOAC plasma concentration at admission. Secondary intracranial hemorrhages and functional outcomes at 3 months were assessed. Since 2023, patients have been treated according to a modified local standard operating procedure at our hospital, allowing for IVT despite DOAC pretreatment regardless of DOAC plasma levels or the use of reversal agents.ResultsOf 1821 patients treated with acute recanalization procedures during the study period, N = 35 had received IVT with (18) or without (17) additional endovascular therapy. Among these patients with a wide age range (42-97 years) and DOAC plasma concentrations up to 369 ng/ml, only one developed symptomatic intracranial hemorrhage. A favorable outcome (modified Rankin scale score 0-2) after 3 months was observed in 57% (20) of the patients.ConclusionIVT despite direct oral anticoagulation seems to be safe, even at advanced age and high DOAC plasma levels.","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"28 1","pages":"17562864241276206"},"PeriodicalIF":5.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of patisiran for ATTRv-PN: a systematic review and meta-analysis.","authors":"Xinyue Huang,Chong Sun,Haofeng Chen,Chongbo Zhao,Jie Lin","doi":"10.1177/17562864241273079","DOIUrl":"https://doi.org/10.1177/17562864241273079","url":null,"abstract":"BackgroundHereditary transthyretin amyloidosis (ATTRv; v for variant) with polyneuropathy is a rare, progressive, and fatal autosomal dominant disorder. Therapies such as liver transplantation and TTR stabilizations have limitations. Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, evidence on patisiran's efficacy and safety for ATTRv-PN remains limited.ObjectivesThis study aimed to further clarify patisiran's efficacy and safety for ATTRv-PN by meta-analysis.DesignSystematic review and meta-analysis.MethodsAfter literature searches in PubMed, Ovid MEDLINE, Embase, JBI EBP, Cochrane, and ClinicalTrials.gov databases on 7 June 2024, 11 studies with 503 patients were included and clinical data were extracted.ResultsResults showed an 88% (95% confidence interval (CI): 81%-94%) pooled responsiveness rate. The standardized mean difference of modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) scores was -0.18 (95% CI: -0.32 to -0.03, p-value 0.018) and Norfolk Quality of Life-Diabetic Neuropathy was -0.21 (95% CI: -0.35 to -0.08, p-value 0.002). In total, 413 adverse events (AEs) (84.8%), 158 serious AEs (32.4%), and 37 deaths (7.6%) were recorded. Most of AEs were mild to moderate. No deaths were attributed to patisiran. However, there is no statistically significant improvement in Neuropathy Impairment Scores.ConclusionIn conclusion, patisiran was effective and safe for patients with ATTRv-PN. More large-scale clinical trials and long-term studies are necessary to further validate patisiran's efficacy and safety.Trial registrationPROSPERO registration ID: CRD42023428838.","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 1","pages":"17562864241273079"},"PeriodicalIF":5.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis: a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study.","authors":"Ali A Habib,Sabrina Sacconi,Giovanni Antonini,Elena Cortés-Vicente,Julian Grosskreutz,Zabeen K Mahuwala,Renato Mantegazza,Robert M Pascuzzi,Kimiaki Utsugisawa,John Vissing,Tuan Vu,Heinz Wiendl,Marion Boehnlein,Bernhard Greve,Franz Woltering,Vera Bril","doi":"10.1177/17562864241273036","DOIUrl":"https://doi.org/10.1177/17562864241273036","url":null,"abstract":"BackgroundMuscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG.ObjectivesTo assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study.DesignA randomised, double-blind, placebo-controlled phase III study.MethodsPatients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-‍ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed.ResultsOverall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred.ConclusionThis subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies.Trial registrationClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials‌register.eu/ctr-search/trial/2019-000968-18/GB).","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"39 1","pages":"17562864241273036"},"PeriodicalIF":5.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}