Pub Date : 2023-09-26eCollection Date: 2023-01-01DOI: 10.1177/17562864231198963
Richard Nicholas, Jeff Rodgers, James Witts, Annalaura Lerede, Tim Friede, Jan Hillert, Lars Forsberg, Anna Glaser, Ali Manouchehrinia, Ryan Ramanujam, Tim Spelman, Pernilla Klyve, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Helmut Butzkueven, Anneke Van Der Walt, Vladimir Bezlyak, Carol Lines, Rod Middleton
Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access.
Methods: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression.
Results: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 - UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment.
Discussion: This highlights the importance of a healthcare system's approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.
引言:多发性硬化症(MS)疾病改良治疗(DMT)的处方指南集中在复发-缓解型MS(RRMS)的临床诊断上。DMT处方指南和监测因国家而异。将病程诊断方法标准化,例如,分配RRMS或继发性进行性MS(SPMS)诊断,可以检查卫生系统特征对所述临床诊断和治疗途径的影响。方法:我们分析了来自五个国家(捷克共和国、丹麦、德国、瑞典和英国)的六个队列的初步诊断为RRMS患者的登记数据。我们利用预先存在的算法(决策树,DT)对我们的方法进行了标准化,以确定患者对RRMS或继发性进行性MS(SPMS)的诊断。我们确定了DMT处方的五个全球驱动因素:供应、可用性、资金、监测和审计,并使用荟萃分析和单变量荟萃分析对这些概念的数据进行了分析。结果:在64235名患者中,我们发现国家之间DMT的使用存在差异,RRMS的使用率较高,SPMS的使用率较低,与其他寄存器相比,在英国的使用量相应地更低。女性等因素(p = 0.041),通过扩展残疾状态量表(EDSS)得分增加残疾(p = 0.004),并且存在监测(p = 0.029)影响接收DMT的可能性。标准化诊断显示,从临床RRMS到DT-SPMS的重新分类率存在差异,瑞典的重新分类比率最低(瑞典0.009,范围:丹麦0.103-英国门户网站0.311) p 讨论:这突出了医疗系统验证多发性硬化症病程临床标签的方法在促进适当处方方面的重要性,在不确定的情况下允许一定的灵活性,以确保继续获得治疗。
{"title":"The impact of healthcare systems on the clinical diagnosis and disease-modifying treatment usage in relapse-onset multiple sclerosis: a real-world perspective in five registries across Europe.","authors":"Richard Nicholas, Jeff Rodgers, James Witts, Annalaura Lerede, Tim Friede, Jan Hillert, Lars Forsberg, Anna Glaser, Ali Manouchehrinia, Ryan Ramanujam, Tim Spelman, Pernilla Klyve, Jiri Drahota, Dana Horakova, Hanna Joensen, Luigi Pontieri, Melinda Magyari, David Ellenberger, Alexander Stahmann, Helmut Butzkueven, Anneke Van Der Walt, Vladimir Bezlyak, Carol Lines, Rod Middleton","doi":"10.1177/17562864231198963","DOIUrl":"https://doi.org/10.1177/17562864231198963","url":null,"abstract":"<p><strong>Introduction: </strong>Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access.</p><p><strong>Methods: </strong>We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression.</p><p><strong>Results: </strong>In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (<i>p</i> = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (<i>p</i> = 0.004), and the presence of monitoring (<i>p</i> = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 - UK portal 0.311). Those with higher EDSS at index (<i>p</i> < 0.03) and female gender (<i>p</i> < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment.</p><p><strong>Discussion: </strong>This highlights the importance of a healthcare system's approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/bc/10.1177_17562864231198963.PMC10524069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144254","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}
Pub Date : 2023-09-21eCollection Date: 2023-01-01DOI: 10.1177/17562864231194823
Alasdair J Coles, Anat Achiron, Anthony Traboulsee, Barry A Singer, Carlo Pozzilli, Celia Oreja-Guevara, Gavin Giovannoni, Giancarlo Comi, Mark S Freedman, Tjalf Ziemssen, Debora Shiota, Andreea M Rawlings, Alana T Wong, Magdalena Chirieac, Xavier Montalban
Background and objectives: Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants ('alemtuzumab-only') could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab ('IFN-alemtuzumab'). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5-7 years (11-13 years after alemtuzumab/IFN initiation).
Methods: Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening [CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0], and 6-month confirmed disease improvement [CDI; >1.0-point EDSS decrease (baseline score ⩾2.0)].
Results: 43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3-13 for the alemtuzumab-only [0.17; 95% confidence interval (CI) 0.15-0.20] and IFN-alemtuzumab (0.14; 0.11-0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent.
Conclusion: Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11-13 years, and most participants did not require more than one additional course.
{"title":"Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study.","authors":"Alasdair J Coles, Anat Achiron, Anthony Traboulsee, Barry A Singer, Carlo Pozzilli, Celia Oreja-Guevara, Gavin Giovannoni, Giancarlo Comi, Mark S Freedman, Tjalf Ziemssen, Debora Shiota, Andreea M Rawlings, Alana T Wong, Magdalena Chirieac, Xavier Montalban","doi":"10.1177/17562864231194823","DOIUrl":"10.1177/17562864231194823","url":null,"abstract":"<p><strong>Background and objectives: </strong>Alemtuzumab demonstrated superior efficacy <i>versus</i> subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants ('alemtuzumab-only') could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab ('IFN-alemtuzumab'). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5-7 years (11-13 years after alemtuzumab/IFN initiation).</p><p><strong>Methods: </strong>Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening [CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0], and 6-month confirmed disease improvement [CDI; >1.0-point EDSS decrease (baseline score ⩾2.0)].</p><p><strong>Results: </strong>43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3-13 for the alemtuzumab-only [0.17; 95% confidence interval (CI) 0.15-0.20] and IFN-alemtuzumab (0.14; 0.11-0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent.</p><p><strong>Conclusion: </strong>Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11-13 years, and most participants did not require more than one additional course.</p><p><strong>Clinicaltrialsgov identifiers: </strong>NCT00530348; NCT00548405; NCT00930553; NCT02255656.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d9/fc/10.1177_17562864231194823.PMC10515516.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150266","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}
Pub Date : 2023-09-21eCollection Date: 2023-01-01DOI: 10.1177/17562864231195513
Clara Grazia Chisari, Joe Guadagno, Peyman Adjamian, Carlos Vila Silvan, Teresa Greco, Makarand Bagul, Francesco Patti
Background: Over 80% of individuals with multiple sclerosis (MS) experience MS-associated spasticity (MSS). In many European countries, after failure of first-line treatments, moderate or severe MSS can be treated with nabiximols, a cannabis-based add-on treatment.
Objective: This post hoc analysis assessed the shift of participants treated with nabiximols from higher (severe or moderate) to lower (moderate or mild/none) spasticity.
Methods: Previously published data from two randomised controlled trials (RCTs), GWSP0604 (NCT00681538) and SAVANT (EudraCT2015-004451-40), and one large real-world study (consistent with EU label), all enriched for responders, were re-analysed. Spasticity severity, measured using the 0-10 numerical rating scale (spasticity NRS), was categorised as none/mild (score <4), moderate (score ⩾4-7), or severe (score ⩾7).
Results: In the two RCTs, the shift of participants with severe MSS into a lower category was significantly greater at week 12 for those receiving nabiximols versus placebo [GWSP0604: OR (95% CI), 4.4 (1.4, 14.2), p = 0.0125; SAVANT: 5.2 (1.2, 22.3), p = 0.0267]. In all three studies, over 80% of assessed patients with severe spasticity at baseline reported a shift into a lower category of spasticity after 12 weeks.
Conclusions: A meaningful proportion of MSS patients treated with nabiximols shifted to a lower category of spasticity severity, typically maintained to the end of the 12-week study period.
{"title":"A <i>post hoc</i> evaluation of the shift in spasticity category in individuals with multiple sclerosis-related spasticity treated with nabiximols.","authors":"Clara Grazia Chisari, Joe Guadagno, Peyman Adjamian, Carlos Vila Silvan, Teresa Greco, Makarand Bagul, Francesco Patti","doi":"10.1177/17562864231195513","DOIUrl":"https://doi.org/10.1177/17562864231195513","url":null,"abstract":"<p><strong>Background: </strong>Over 80% of individuals with multiple sclerosis (MS) experience MS-associated spasticity (MSS). In many European countries, after failure of first-line treatments, moderate or severe MSS can be treated with nabiximols, a cannabis-based add-on treatment.</p><p><strong>Objective: </strong>This <i>post hoc</i> analysis assessed the shift of participants treated with nabiximols from higher (severe or moderate) to lower (moderate or mild/none) spasticity.</p><p><strong>Methods: </strong>Previously published data from two randomised controlled trials (RCTs), GWSP0604 (NCT00681538) and SAVANT (EudraCT2015-004451-40), and one large real-world study (consistent with EU label), all enriched for responders, were re-analysed. Spasticity severity, measured using the 0-10 numerical rating scale (spasticity NRS), was categorised as none/mild (score <4), moderate (score ⩾4-7), or severe (score ⩾7).</p><p><strong>Results: </strong>In the two RCTs, the shift of participants with severe MSS into a lower category was significantly greater at week 12 for those receiving nabiximols <i>versus</i> placebo [GWSP0604: OR (95% CI), 4.4 (1.4, 14.2), <i>p</i> = 0.0125; SAVANT: 5.2 (1.2, 22.3), <i>p</i> = 0.0267]. In all three studies, over 80% of assessed patients with severe spasticity at baseline reported a shift into a lower category of spasticity after 12 weeks.</p><p><strong>Conclusions: </strong>A meaningful proportion of MSS patients treated with nabiximols shifted to a lower category of spasticity severity, typically maintained to the end of the 12-week study period.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/03/10.1177_17562864231195513.PMC10515604.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152181","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}
Pub Date : 2023-09-15eCollection Date: 2023-01-01DOI: 10.1177/17562864231193816
Meng Wang, Caiyun Liu, Meijuan Zou, Zixuan Niu, Jie Zhu, Tao Jin
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It mainly affects young adults, imposing a heavy burden on families and society. The epidemiology, clinical features, and management of MS are distinct among different countries. Although MS is a rare disease in China, there are 1.4 billion people in China, so the total number of MS patients is not small. Because of the lack of specific diagnostic biomarkers for MS, there is a high misdiagnosis rate in China, as in other regions. Due to different genetic backgrounds, the clinical manifestations of MS in Chinese are different from those in the West. Herein, this review aims to summarize the disease comprehensively, including clinical profile and the status of disease-modifying therapies in China based on published population-based observation and cohort studies, and also to compare with data from other countries and regions, thus providing help to develop diagnostic guideline and the novel therapeutic drugs. Meanwhile, we also discuss the problems and challenges we face, specifically for the diagnosis and treatment of MS in the middle- and low-income countries.
{"title":"Recent progress in epidemiology, clinical features, and therapy of multiple sclerosis in China.","authors":"Meng Wang, Caiyun Liu, Meijuan Zou, Zixuan Niu, Jie Zhu, Tao Jin","doi":"10.1177/17562864231193816","DOIUrl":"10.1177/17562864231193816","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. It mainly affects young adults, imposing a heavy burden on families and society. The epidemiology, clinical features, and management of MS are distinct among different countries. Although MS is a rare disease in China, there are 1.4 billion people in China, so the total number of MS patients is not small. Because of the lack of specific diagnostic biomarkers for MS, there is a high misdiagnosis rate in China, as in other regions. Due to different genetic backgrounds, the clinical manifestations of MS in Chinese are different from those in the West. Herein, this review aims to summarize the disease comprehensively, including clinical profile and the status of disease-modifying therapies in China based on published population-based observation and cohort studies, and also to compare with data from other countries and regions, thus providing help to develop diagnostic guideline and the novel therapeutic drugs. Meanwhile, we also discuss the problems and challenges we face, specifically for the diagnosis and treatment of MS in the middle- and low-income countries.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/d2/10.1177_17562864231193816.PMC10504852.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339573","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}
Pub Date : 2023-09-13eCollection Date: 2023-01-01DOI: 10.1177/17562864231197994
Shaddy El-Masri, Matthew Wilson, Jonathan Goh, Paul Sanfilippo, Anthony Fok, Thomas Hardy, Rahul Chakrabarti, Anneke Van Der Walt
Background: Optic nerve sheath fenestration (ONSF) longitudinal outcomes remain unclear and are vital in the assessment of vision failure in patients with raised intracranial pressure (ICP). Furthermore, limited observational data exists regarding its use in other causes of raised ICP.
Objective: To determine the efficacy and safety of ONSF for idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), and other indications.
Method: Multicentre study from a tertiary hospital and specialty eye referral hospital in Melbourne, Australia, from July 2000 to December 2020. A total of 116 eyes from 70 patients undergoing ONSF were retrospectively reviewed with patient demographics, surgery indications, visual acuity (VA), visual fields, fundus photos of optic discs, retinal nerve fibre layer (RNFL) thickness, average thickness of optic discs on optical coherence tomography (OCT), and complications recorded. Parametric tests were used to compare the treatment groups pre- and post-operatively.
Results: A total of 116 eyes from 70 patients underwent ONSF, which involved 92 eyes with IIH, 9 eyes with CVST, and 15 eyes with other aetiologies ('Other'). Post ONSF, there was a best corrected visual acuity (BCVA) improvement or stabilisation in 84% of patients in all groups, with 50% achieving a BCVA of 6/6 or better at the final follow-up. RNFL, visual fields, and fundus grades all trended towards improvement, with most improvement noted by day 360. Common complications included transient diplopia (n = 29, 25%) and worsening of visual function requiring further cerebrospinal fluid (CSF) diversion procedures (n = 20, 17%). Complications were most significant in the 'Other' group with 1/3 of eyes requiring further CSF diversion procedures.
Conclusion: Our data demonstrates effectiveness in the use of ONSF in papilloedema with visual failure due to IIH or CVST and when other CSF diversion procedures or medical therapies have failed.
{"title":"A 20-year multicentre retrospective review of optic nerve sheath fenestration outcomes.","authors":"Shaddy El-Masri, Matthew Wilson, Jonathan Goh, Paul Sanfilippo, Anthony Fok, Thomas Hardy, Rahul Chakrabarti, Anneke Van Der Walt","doi":"10.1177/17562864231197994","DOIUrl":"10.1177/17562864231197994","url":null,"abstract":"<p><strong>Background: </strong>Optic nerve sheath fenestration (ONSF) longitudinal outcomes remain unclear and are vital in the assessment of vision failure in patients with raised intracranial pressure (ICP). Furthermore, limited observational data exists regarding its use in other causes of raised ICP.</p><p><strong>Objective: </strong>To determine the efficacy and safety of ONSF for idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), and other indications.</p><p><strong>Method: </strong>Multicentre study from a tertiary hospital and specialty eye referral hospital in Melbourne, Australia, from July 2000 to December 2020. A total of 116 eyes from 70 patients undergoing ONSF were retrospectively reviewed with patient demographics, surgery indications, visual acuity (VA), visual fields, fundus photos of optic discs, retinal nerve fibre layer (RNFL) thickness, average thickness of optic discs on optical coherence tomography (OCT), and complications recorded. Parametric tests were used to compare the treatment groups pre- and post-operatively.</p><p><strong>Results: </strong>A total of 116 eyes from 70 patients underwent ONSF, which involved 92 eyes with IIH, 9 eyes with CVST, and 15 eyes with other aetiologies ('Other'). Post ONSF, there was a best corrected visual acuity (BCVA) improvement or stabilisation in 84% of patients in all groups, with 50% achieving a BCVA of 6/6 or better at the final follow-up. RNFL, visual fields, and fundus grades all trended towards improvement, with most improvement noted by day 360. Common complications included transient diplopia (<i>n</i> = 29, 25%) and worsening of visual function requiring further cerebrospinal fluid (CSF) diversion procedures (<i>n</i> = 20, 17%). Complications were most significant in the 'Other' group with 1/3 of eyes requiring further CSF diversion procedures.</p><p><strong>Conclusion: </strong>Our data demonstrates effectiveness in the use of ONSF in papilloedema with visual failure due to IIH or CVST and when other CSF diversion procedures or medical therapies have failed.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/a9/10.1177_17562864231197994.PMC10501074.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339574","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}
Pub Date : 2023-07-24eCollection Date: 2023-01-01DOI: 10.1177/17562864231181170
Bitao Bu, Chao Quan, Wenyu Li, Qiuming Zeng, Ziyan Shi, Bo Chen, Lei Zhou, Luya Jin, Hongyu Zhou, Huan Yang
Background: Teriflunomide is a first-line oral immunomodulatory agent approved in China for the treatment of relapsing multiple sclerosis.
Objective: To compare the treatment outcomes of teriflunomide and no disease-modifying therapy (DMT) treatment (in first year) in multi-center real-world Chinese multiple sclerosis patients.
Design: Retrospective study.
Methods: This study was conducted in five tertiary hospitals in different geographical regions of China. We collected clinical data of patients treated with teriflunomide and no DMT treatment (in first year) between 1 January 2017 and 31 August 2021. The effectiveness of teriflunomide was described. Potential factors influencing the effectiveness of teriflunomide were investigated.
Results: A total of 372 patients treated with teriflunomide and 148 no DMT treatment patients were included. A total of 292 patients were treated with teriflunomide for at least 6 months, described as a stable teriflunomide cohort. The annualized relapse rate was significantly lower in the stable teriflunomide cohort than in the no DMT treatment cohort (0.23 ± 0.47 versus 0.87 ± 0.67, p < 0.001). The mean Expanded Disability Status Scale (EDSS) score of the stable teriflunomide cohort (1.77 ± 1.62) was slightly different from that of the no DMT treatment cohort (2.09 ± 2.00). A previous annualized relapse rate of ⩾1, a previous EDSS score of ⩾2, and a long disease duration of ⩾5 years were associated with better clinical effectiveness.
Conclusion: Teriflunomide is associated with a lower relapse rate and less disability accumulation in Chinese patients with multiple sclerosis.
{"title":"The effectiveness of teriflunomide in patients with multiple sclerosis in China: a real-world comparison to no DMT treatment in the first year after diagnosis.","authors":"Bitao Bu, Chao Quan, Wenyu Li, Qiuming Zeng, Ziyan Shi, Bo Chen, Lei Zhou, Luya Jin, Hongyu Zhou, Huan Yang","doi":"10.1177/17562864231181170","DOIUrl":"10.1177/17562864231181170","url":null,"abstract":"<p><strong>Background: </strong>Teriflunomide is a first-line oral immunomodulatory agent approved in China for the treatment of relapsing multiple sclerosis.</p><p><strong>Objective: </strong>To compare the treatment outcomes of teriflunomide and no disease-modifying therapy (DMT) treatment (in first year) in multi-center real-world Chinese multiple sclerosis patients.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Methods: </strong>This study was conducted in five tertiary hospitals in different geographical regions of China. We collected clinical data of patients treated with teriflunomide and no DMT treatment (in first year) between 1 January 2017 and 31 August 2021. The effectiveness of teriflunomide was described. Potential factors influencing the effectiveness of teriflunomide were investigated.</p><p><strong>Results: </strong>A total of 372 patients treated with teriflunomide and 148 no DMT treatment patients were included. A total of 292 patients were treated with teriflunomide for at least 6 months, described as a stable teriflunomide cohort. The annualized relapse rate was significantly lower in the stable teriflunomide cohort than in the no DMT treatment cohort (0.23 ± 0.47 <i>versus</i> 0.87 ± 0.67, <i>p</i> < 0.001). The mean Expanded Disability Status Scale (EDSS) score of the stable teriflunomide cohort (1.77 ± 1.62) was slightly different from that of the no DMT treatment cohort (2.09 ± 2.00). A previous annualized relapse rate of ⩾1, a previous EDSS score of ⩾2, and a long disease duration of ⩾5 years were associated with better clinical effectiveness.</p><p><strong>Conclusion: </strong>Teriflunomide is associated with a lower relapse rate and less disability accumulation in Chinese patients with multiple sclerosis.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/90/10.1177_17562864231181170.PMC10387708.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929300","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}
Granulomatosis or eosinophilic granulomatosis with polyangiitis (GPA/EGPA) can affect multiple organs resulting in heterogeneous symptoms and phenotypes. Pituitary gland dysfunction rarely occurs in GPA (1-3%) and even less in EGPA (two case reports). Here, we report a case of a 51-year-old female patient with a four-year history of EGPA who presented with new polydipsia and polyuria. Laboratory testing and magnetic resonance imaging (MRI) confirmed pituitary gland dysfunction caused by a hypophysitis. Therapeutic adjustment with a switch from dupilumab to mepolizumab resulted in a decrease in clinical symptoms, inflammation in MRI, and normalization of C-reactive protein in serum. This case underlines hypophysitis as a rare organ involvement also in EGPA. Moreover, this case demonstrates the responsiveness of neuroinflammatory manifestations to the recently approved anti-interleukin-5 monoclonal antibody mepolizumab as a new potential treatment option.
{"title":"Mepolizumab as an effective treatment in a case of hypophysitis in eosinophilic granulomatosis with polyangiitis.","authors":"Jessy Chen, Tobias Alexander, Thula Walter-Rittel, Athanasia Ziagaki, Volker Siffrin","doi":"10.1177/17562864231182519","DOIUrl":"10.1177/17562864231182519","url":null,"abstract":"<p><p>Granulomatosis or eosinophilic granulomatosis with polyangiitis (GPA/EGPA) can affect multiple organs resulting in heterogeneous symptoms and phenotypes. Pituitary gland dysfunction rarely occurs in GPA (1-3%) and even less in EGPA (two case reports). Here, we report a case of a 51-year-old female patient with a four-year history of EGPA who presented with new polydipsia and polyuria. Laboratory testing and magnetic resonance imaging (MRI) confirmed pituitary gland dysfunction caused by a hypophysitis. Therapeutic adjustment with a switch from dupilumab to mepolizumab resulted in a decrease in clinical symptoms, inflammation in MRI, and normalization of C-reactive protein in serum. This case underlines hypophysitis as a rare organ involvement also in EGPA. Moreover, this case demonstrates the responsiveness of neuroinflammatory manifestations to the recently approved anti-interleukin-5 monoclonal antibody mepolizumab as a new potential treatment option.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46653899","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}
Pub Date : 2023-01-02eCollection Date: 2023-01-01DOI: 10.1177/17562864221137129
Felix Kohle, Marinos C Dalakas, Helmar C Lehmann
Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number of studies that explored the efficacy of DMTs in animal models of AN but also in some CIDP patients. We here review the available preclinical and clinical data of approved MS therapeutics in terms of their applicability to AN, especially CIDP. Promising therapeutic approaches appear to be B cell-directed and complement-targeting strategies, such as anti-CD20/anti-CD19 agents, Bruton's tyrosine kinase inhibitors and anti-C5 agents, as they exert their effects in the periphery. This is a major advantage because, in contrast to MS, their action in the periphery is sufficient to exert significant immunomodulation.
尽管慢性炎症性脱髓鞘多发性神经病(CIDP)和其他常见自身免疫性神经病(AN)的治疗取得了进展,但仍有许多患者对现有疗法的反应并不令人满意。从其他自身免疫性疾病,尤其是多发性硬化症(MS)和神经性脊髓炎视网膜频谱病变(NMOSD)中提取疾病修饰疗法(DMTs)的再利用是一种很有前景的策略,它可能会加速为自身免疫性神经病变提供新的治疗选择。由于这些疾病的发病机制具有相似性,而且治疗 MS 和 NMOSD 患者积累了丰富的上市后经验,因此这种方法似乎很有吸引力。一些研究不仅探讨了DMTs在AN动物模型中的疗效,也探讨了DMTs在一些CIDP患者中的疗效,这些研究也加强了这一想法。我们在此回顾了已获批准的多发性硬化症治疗药物的现有临床前和临床数据,以了解这些药物对自闭症,尤其是 CIDP 的适用性。有希望的治疗方法似乎是B细胞导向和补体靶向策略,如抗CD20/抗CD19制剂、布鲁顿酪氨酸激酶抑制剂和抗C5制剂,因为它们在外周发挥效应。这是一项重大优势,因为与多发性硬化症相比,它们在外周的作用足以产生显著的免疫调节效果。
{"title":"Repurposing MS immunotherapies for CIDP and other autoimmune neuropathies: unfulfilled promise or efficient strategy?","authors":"Felix Kohle, Marinos C Dalakas, Helmar C Lehmann","doi":"10.1177/17562864221137129","DOIUrl":"10.1177/17562864221137129","url":null,"abstract":"<p><p>Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number of studies that explored the efficacy of DMTs in animal models of AN but also in some CIDP patients. We here review the available preclinical and clinical data of approved MS therapeutics in terms of their applicability to AN, especially CIDP. Promising therapeutic approaches appear to be B cell-directed and complement-targeting strategies, such as anti-CD20/anti-CD19 agents, Bruton's tyrosine kinase inhibitors and anti-C5 agents, as they exert their effects in the periphery. This is a major advantage because, in contrast to MS, their action in the periphery is sufficient to exert significant immunomodulation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/7f/10.1177_17562864221137129.PMC9810996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509237","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}
Background: The prevalence of intracranial aneurysms is approximately 3% worldwide. Posterior circulation (PC) aneurysms have a higher risk of treatment complications than anterior circulation aneurysms. Improving the survival rate and quality of life of patients with PC aneurysms remains one of the most important issues in the field.
Objectives: Flow diverter (FD) treatment of PC aneurysms remains controversial. We aimed to investigate the effects of FD treatment and analyze differences among different application methods or aneurysm types in PC aneurysms.
Design: This is a multicenter retrospective study.
Methods: Patients with PC aneurysms treated with the pipeline embolization device (PED) or Tubridge embolization device (TED) between 2015 and 2020 in five neurovascular centers were retrospectively enrolled. The primary outcomes were major perioperative complication, clinical outcome, and aneurysm occlusion rates. Univariable and multivariable logistic regression analyses were used to determine the risk factors of each outcome.
Results: In total, 252 aneurysms were included. Major perioperative complication, favorable clinical outcome, and complete occlusion rates were 7.5%, 91.0%, and 79.1%, respectively. Compared with other types of aneurysms, dissecting aneurysms had the best clinical outcome and highest occlusion rate. Both clinical and angiographic outcomes were independently associated with the aneurysm location at the basilar artery. Aneurysm size was not associated with any outcome. TED had similar clinical and angiographic outcomes compared with PED but more perioperative major complications. Tandem treatment and coiling assistance may have poorer clinical outcomes but similar occlusion rates. Single- and multiple-stent treatments had similar outcomes.
Conclusion: FD treatment of PC aneurysms achieved favorable clinical outcomes and long-term aneurysm occlusion rates with acceptable perioperative complication rates, especially in dissecting and non-basilar artery aneurysms. There was no additional improvement in outcomes with coiling assistance, multi-stent application, or tandem treatment. Therefore, the use of PC aneurysms should be carefully considered.
{"title":"Flow diversion for posterior circulation aneurysms: a multicenter retrospective study.","authors":"Peng Qi, Xin Tong, Xin Liang, Xiaopeng Xue, Zhongxue Wu, Xin Feng, Meng Zhang, Zhiqun Jiang, Daming Wang, Aihua Liu","doi":"10.1177/17562864231176187","DOIUrl":"https://doi.org/10.1177/17562864231176187","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of intracranial aneurysms is approximately 3% worldwide. Posterior circulation (PC) aneurysms have a higher risk of treatment complications than anterior circulation aneurysms. Improving the survival rate and quality of life of patients with PC aneurysms remains one of the most important issues in the field.</p><p><strong>Objectives: </strong>Flow diverter (FD) treatment of PC aneurysms remains controversial. We aimed to investigate the effects of FD treatment and analyze differences among different application methods or aneurysm types in PC aneurysms.</p><p><strong>Design: </strong>This is a multicenter retrospective study.</p><p><strong>Methods: </strong>Patients with PC aneurysms treated with the pipeline embolization device (PED) or Tubridge embolization device (TED) between 2015 and 2020 in five neurovascular centers were retrospectively enrolled. The primary outcomes were major perioperative complication, clinical outcome, and aneurysm occlusion rates. Univariable and multivariable logistic regression analyses were used to determine the risk factors of each outcome.</p><p><strong>Results: </strong>In total, 252 aneurysms were included. Major perioperative complication, favorable clinical outcome, and complete occlusion rates were 7.5%, 91.0%, and 79.1%, respectively. Compared with other types of aneurysms, dissecting aneurysms had the best clinical outcome and highest occlusion rate. Both clinical and angiographic outcomes were independently associated with the aneurysm location at the basilar artery. Aneurysm size was not associated with any outcome. TED had similar clinical and angiographic outcomes compared with PED but more perioperative major complications. Tandem treatment and coiling assistance may have poorer clinical outcomes but similar occlusion rates. Single- and multiple-stent treatments had similar outcomes.</p><p><strong>Conclusion: </strong>FD treatment of PC aneurysms achieved favorable clinical outcomes and long-term aneurysm occlusion rates with acceptable perioperative complication rates, especially in dissecting and non-basilar artery aneurysms. There was no additional improvement in outcomes with coiling assistance, multi-stent application, or tandem treatment. Therefore, the use of PC aneurysms should be carefully considered.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/06/10.1177_17562864231176187.PMC10262625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291220","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}
Pub Date : 2023-01-01DOI: 10.1177/17562864221149781
Natalie L Goedeker, Sachi D Dharia, Danielle A Griffin, Jesantha Coy, Todd Truesdale, Rajan Parikh, Kasen Whitehouse, Sourav Santra, Damon R Asher, Craig M Zaidman
Background: Adeno-associated virus (AAV) vectors are a promising platform for in vivo transfer of transgenes designed to treat diseases. Pre-existing humoral immunity to these vectors can potentially impact the safety and efficacy of gene therapies. Consequently, individuals with pre-existing antibodies to the specific AAV serotypes used may be excluded from clinical trials and treatments. Recombinant AAV serotype rh74 (rAAVrh74), a vector originally isolated from rhesus monkeys and potentially less immunogenic than other serotypes isolated from humans (e.g. AAV2, AAV5, and AAV9), efficiently transduces muscle and is being investigated for use in gene therapy for Duchenne muscular dystrophy (DMD).
Objective: To evaluate prevalence of total binding antibodies (neutralizing and non-neutralizing) against rAAVrh74 in patients with DMD.
Methods: Eligible individuals (N = 107) were ⩾ 4 to < 18 years old with genetically confirmed DMD and were excluded from the study if they lived with a person who had known exposure to rAAVrh74 or other gene transfer therapy, or if they received prior treatment with gene transfer therapy. A single blood sample was obtained from each participant, and anti-rAAVrh74 total binding antibodies were measured by enzyme-linked immunosorbent assay. Total binding antibody level < 1:400 was defined as not elevated or seronegative. Primary endpoint was the percentage of subjects with elevated total antibody titers to rAAVrh74.
Results: A large preponderance (86.1%) of patients with DMD in this data set was seronegative for anti-rAAVrh74 total binding antibodies. These patients would potentially meet the antibody status eligibility criterion for entry into rAAVrh74-based gene therapy clinical trials.
Conclusion: Measuring total binding antibodies is a more comprehensive approach to assess pre-existing immune response versus measuring neutralizing antibodies alone. The low seroprevalence of total binding antibodies against rAAVrh74 shown here supports the broad applicability of rAAVrh74-based gene transfer therapy for patients with DMD and potentially other neuromuscular diseases.
{"title":"Evaluation of rAAVrh74 gene therapy vector seroprevalence by measurement of total binding antibodies in patients with Duchenne muscular dystrophy.","authors":"Natalie L Goedeker, Sachi D Dharia, Danielle A Griffin, Jesantha Coy, Todd Truesdale, Rajan Parikh, Kasen Whitehouse, Sourav Santra, Damon R Asher, Craig M Zaidman","doi":"10.1177/17562864221149781","DOIUrl":"https://doi.org/10.1177/17562864221149781","url":null,"abstract":"<p><strong>Background: </strong>Adeno-associated virus (AAV) vectors are a promising platform for <i>in vivo</i> transfer of transgenes designed to treat diseases. Pre-existing humoral immunity to these vectors can potentially impact the safety and efficacy of gene therapies. Consequently, individuals with pre-existing antibodies to the specific AAV serotypes used may be excluded from clinical trials and treatments. Recombinant AAV serotype rh74 (rAAVrh74), a vector originally isolated from rhesus monkeys and potentially less immunogenic than other serotypes isolated from humans (e.g. AAV2, AAV5, and AAV9), efficiently transduces muscle and is being investigated for use in gene therapy for Duchenne muscular dystrophy (DMD).</p><p><strong>Objective: </strong>To evaluate prevalence of total binding antibodies (neutralizing and non-neutralizing) against rAAVrh74 in patients with DMD.</p><p><strong>Methods: </strong>Eligible individuals (<i>N</i> = 107) were ⩾ 4 to < 18 years old with genetically confirmed DMD and were excluded from the study if they lived with a person who had known exposure to rAAVrh74 or other gene transfer therapy, or if they received prior treatment with gene transfer therapy. A single blood sample was obtained from each participant, and anti-rAAVrh74 total binding antibodies were measured by enzyme-linked immunosorbent assay. Total binding antibody level < 1:400 was defined as not elevated or seronegative. Primary endpoint was the percentage of subjects with elevated total antibody titers to rAAVrh74.</p><p><strong>Results: </strong>A large preponderance (86.1%) of patients with DMD in this data set was seronegative for anti-rAAVrh74 total binding antibodies. These patients would potentially meet the antibody status eligibility criterion for entry into rAAVrh74-based gene therapy clinical trials.</p><p><strong>Conclusion: </strong>Measuring total binding antibodies is a more comprehensive approach to assess pre-existing immune response <i>versus</i> measuring neutralizing antibodies alone. The low seroprevalence of total binding antibodies against rAAVrh74 shown here supports the broad applicability of rAAVrh74-based gene transfer therapy for patients with DMD and potentially other neuromuscular diseases.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/b9/10.1177_17562864221149781.PMC9880577.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589412","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}