Pub Date : 2026-03-01DOI: 10.1016/S1474-4422(25)00477-6
Daniele Martinelli, Roberto De Icco, Haidar M Al-Khazali, Sait Ashina, Hans-Christoph Diener, Freda Dodd-Glover, Maria Teresa Goicochea, Bronwyn Jenkins, Antoinette MaassenVanDenBrink, Mi Ji Lee, Aynur Özge, Mario Fernando Prieto Peres, Patricia Pozo-Rosich, Francesca Puledda, Simona Sacco, Todd Schwedt, Gisela M Terwindt, Cristina Tassorelli
Migraine imposes a heavy burden on patients and societies. Preventive treatments aimed at reducing the occurrence of migraine attacks and their intensity have been largely underused, leaving a multitude of people with migraine to rely exclusively on acute treatments, which, when used in excess, might even worsen the clinical situation. Large, randomised trials have established the tolerability and efficacy of calcitonin gene-related peptide (CGRP)-targeting drugs, a new class of migraine-specific treatment. The increased adherence to longer treatment cycles with migraine-specific preventive drugs, such as CGRP-targeting therapies, compared with non-migraine specific treatments has the potential to improve control of the disease. These migraine-specific drugs also provide benefits to individuals with migraine who previously did not benefit from non-specific migraine preventive medications. Increased reliance on preventive treatment with migraine-specific options is progressively optimising the management of migraine for mounting numbers of patients disabled by the disease, thereby improving disease control and their quality of life.
{"title":"Advances in migraine prevention.","authors":"Daniele Martinelli, Roberto De Icco, Haidar M Al-Khazali, Sait Ashina, Hans-Christoph Diener, Freda Dodd-Glover, Maria Teresa Goicochea, Bronwyn Jenkins, Antoinette MaassenVanDenBrink, Mi Ji Lee, Aynur Özge, Mario Fernando Prieto Peres, Patricia Pozo-Rosich, Francesca Puledda, Simona Sacco, Todd Schwedt, Gisela M Terwindt, Cristina Tassorelli","doi":"10.1016/S1474-4422(25)00477-6","DOIUrl":"10.1016/S1474-4422(25)00477-6","url":null,"abstract":"<p><p>Migraine imposes a heavy burden on patients and societies. Preventive treatments aimed at reducing the occurrence of migraine attacks and their intensity have been largely underused, leaving a multitude of people with migraine to rely exclusively on acute treatments, which, when used in excess, might even worsen the clinical situation. Large, randomised trials have established the tolerability and efficacy of calcitonin gene-related peptide (CGRP)-targeting drugs, a new class of migraine-specific treatment. The increased adherence to longer treatment cycles with migraine-specific preventive drugs, such as CGRP-targeting therapies, compared with non-migraine specific treatments has the potential to improve control of the disease. These migraine-specific drugs also provide benefits to individuals with migraine who previously did not benefit from non-specific migraine preventive medications. Increased reliance on preventive treatment with migraine-specific options is progressively optimising the management of migraine for mounting numbers of patients disabled by the disease, thereby improving disease control and their quality of life.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 3","pages":"279-293"},"PeriodicalIF":45.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01DOI: 10.1016/S1474-4422(25)00479-X
Dalia L Rotstein, Raed Alroughani, Georgina Arrambide, Edgar Carnero Contentti, Mashina Chomba, Kazuo Fujihara, Nils E Gilhus, Riadh Gouider, Jeannine M Heckmann, Ho Jin Kim, Hai-Feng Li, Maria Isabel Leite, Mastura Monif, Sasitorn Siritho, Sandra Thiel, Anastasia Vishnevetsky, Shanthi Viswanathan, Sandra Vukusic, Bassem Yamout, Tania Kümpfel, Kerstin Hellwig
Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.
{"title":"Current evidence and knowledge gaps in family planning and pregnancy in myasthenia gravis, NMOSD, and MOGAD.","authors":"Dalia L Rotstein, Raed Alroughani, Georgina Arrambide, Edgar Carnero Contentti, Mashina Chomba, Kazuo Fujihara, Nils E Gilhus, Riadh Gouider, Jeannine M Heckmann, Ho Jin Kim, Hai-Feng Li, Maria Isabel Leite, Mastura Monif, Sasitorn Siritho, Sandra Thiel, Anastasia Vishnevetsky, Shanthi Viswanathan, Sandra Vukusic, Bassem Yamout, Tania Kümpfel, Kerstin Hellwig","doi":"10.1016/S1474-4422(25)00479-X","DOIUrl":"10.1016/S1474-4422(25)00479-X","url":null,"abstract":"<p><p>Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 3","pages":"308-324"},"PeriodicalIF":45.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-07-22DOI: 10.1016/S1474-4422(24)00285-0
Rui Araújo
{"title":"On how a brain beholds beauty.","authors":"Rui Araújo","doi":"10.1016/S1474-4422(24)00285-0","DOIUrl":"10.1016/S1474-4422(24)00285-0","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1085"},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1016/S1474-4422(24)00326-0
Suvankar Pal, Jeremy Chataway, Robert Swingler, Malcolm R Macleod, Neil O Carragher, Giles Hardingham, Bhuvaneish Thangaraj Selvaraj, Colin Smith, Charis Wong, Judith Newton, Dawn Lyle, Amy Stenson, Rachel S Dakin, Amarachi Ihenacho, Shuna Colville, Arpan R Mehta, Nigel Stallard, James R Carpenter, Richard A Parker, Catriona Keerie, Christopher J Weir, Bruce Virgo, Stevie Morris, Nicola Waters, Beverley Gray, Donald MacDonald, Euan MacDonald, Mahesh K B Parmar, Siddharthan Chandran
<p><strong>Background: </strong>Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.</p><p><strong>Methods: </strong>MND SMART is an investigator-led, phase 3, double-blind, placebo-controlled, multiarm, multistage, randomised, adaptive platform trial recruiting at 20 hospital centres in the UK. Individuals older than 18 years with a confirmed diagnosis of either amyotrophic lateral sclerosis classified by the revised El Escorial criteria, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy, regardless of disease duration, were eligible for screening. Participants were randomised (1:1:1) to receive oral trazodone 200 mg once a day, oral memantine 20 mg once a day, or matched placebo using a computer-generated minimisation algorithm delivered via a secure web-based system. Co-primary outcome measures were clinical functioning, measured by rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), and survival. Comparisons were conducted in four stages, with predefined criteria for stopping at the end of stages one and two. We report interim analysis from the stage two results, which was done when 100 participants per group (excluding long survivors, defined as >8 years since diagnosis at baseline) completed a minimum of 12 months of follow-up for the candidate investigational medicinal products. The trial is registered on the European Clinical Trials Registry, 2019-000099-41, and ClinicalTrials.gov, NCT04302870, and is ongoing.</p><p><strong>Findings: </strong>Between Feb 27, 2020, and July 24, 2023 (database lock for interim analysis two), 554 people with a motor neuron disease were randomly allocated to memantine (183 [33%]), trazodone (185 [33%]), or placebo (186 [34%]). The primary interim analysis population comprised 530 participants, of whom 175 (33%) had been allocated memantine, 175 (33%) had been allocated trazodone, and 180 (34%) had been allocated placebo. Over 12 months of follow-up, the mean rate of change per month in ALSFRS-R was -0·650 for memantine, -0·625 for trazodone, and -0·655 for placebo (memantine versus placebo estimated mean difference 0·033, one-sided 90% CI lower level -0·085; one-sided p=0·36; trazodone vs placebo: 0·065, -0·051; one-sided p=0·24). The one-sided p values were both above the significance threshold of 10%, indicating that neither memantine nor trazodone groups met the criteria for continuation. There were 483 participants with at least one adverse event (145 [77%] on placebo, 170 [91%] on memantine, and 168 [9
{"title":"Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.","authors":"Suvankar Pal, Jeremy Chataway, Robert Swingler, Malcolm R Macleod, Neil O Carragher, Giles Hardingham, Bhuvaneish Thangaraj Selvaraj, Colin Smith, Charis Wong, Judith Newton, Dawn Lyle, Amy Stenson, Rachel S Dakin, Amarachi Ihenacho, Shuna Colville, Arpan R Mehta, Nigel Stallard, James R Carpenter, Richard A Parker, Catriona Keerie, Christopher J Weir, Bruce Virgo, Stevie Morris, Nicola Waters, Beverley Gray, Donald MacDonald, Euan MacDonald, Mahesh K B Parmar, Siddharthan Chandran","doi":"10.1016/S1474-4422(24)00326-0","DOIUrl":"10.1016/S1474-4422(24)00326-0","url":null,"abstract":"<p><strong>Background: </strong>Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.</p><p><strong>Methods: </strong>MND SMART is an investigator-led, phase 3, double-blind, placebo-controlled, multiarm, multistage, randomised, adaptive platform trial recruiting at 20 hospital centres in the UK. Individuals older than 18 years with a confirmed diagnosis of either amyotrophic lateral sclerosis classified by the revised El Escorial criteria, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy, regardless of disease duration, were eligible for screening. Participants were randomised (1:1:1) to receive oral trazodone 200 mg once a day, oral memantine 20 mg once a day, or matched placebo using a computer-generated minimisation algorithm delivered via a secure web-based system. Co-primary outcome measures were clinical functioning, measured by rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), and survival. Comparisons were conducted in four stages, with predefined criteria for stopping at the end of stages one and two. We report interim analysis from the stage two results, which was done when 100 participants per group (excluding long survivors, defined as >8 years since diagnosis at baseline) completed a minimum of 12 months of follow-up for the candidate investigational medicinal products. The trial is registered on the European Clinical Trials Registry, 2019-000099-41, and ClinicalTrials.gov, NCT04302870, and is ongoing.</p><p><strong>Findings: </strong>Between Feb 27, 2020, and July 24, 2023 (database lock for interim analysis two), 554 people with a motor neuron disease were randomly allocated to memantine (183 [33%]), trazodone (185 [33%]), or placebo (186 [34%]). The primary interim analysis population comprised 530 participants, of whom 175 (33%) had been allocated memantine, 175 (33%) had been allocated trazodone, and 180 (34%) had been allocated placebo. Over 12 months of follow-up, the mean rate of change per month in ALSFRS-R was -0·650 for memantine, -0·625 for trazodone, and -0·655 for placebo (memantine versus placebo estimated mean difference 0·033, one-sided 90% CI lower level -0·085; one-sided p=0·36; trazodone vs placebo: 0·065, -0·051; one-sided p=0·24). The one-sided p values were both above the significance threshold of 10%, indicating that neither memantine nor trazodone groups met the criteria for continuation. There were 483 participants with at least one adverse event (145 [77%] on placebo, 170 [91%] on memantine, and 168 [9","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1097-1107"},"PeriodicalIF":45.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1016/S1474-4422(24)00391-0
Anneke van der Walt
{"title":"Evobrutinib in multiple sclerosis: challenges and unmet goals.","authors":"Anneke van der Walt","doi":"10.1016/S1474-4422(24)00391-0","DOIUrl":"10.1016/S1474-4422(24)00391-0","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1068-1070"},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1016/S1474-4422(24)00328-4
Xavier Montalban, Patrick Vermersch, Douglas L Arnold, Amit Bar-Or, Bruce A C Cree, Anne H Cross, Eva Kubala Havrdova, Ludwig Kappos, Olaf Stuve, Heinz Wiendl, Jerry S Wolinsky, Frank Dahlke, Claire Le Bolay, Li Shen Loo, Sathej Gopalakrishnan, Yann Hyvert, Andrija Javor, Hans Guehring, Nadia Tenenbaum, Davorka Tomic
<p><strong>Background: </strong>Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis.</p><p><strong>Methods: </strong>EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated).</p><p><strong>Findings: </strong>The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly
背景埃沃布替尼是一种布鲁顿酪氨酸激酶（BTK）抑制剂，在一项二期试验中显示出对复发性多发性硬化症患者的初步疗效。在此，我们旨在比较 evobrutinib 与特立氟胺（teriflunomide）在复发性多发性硬化症患者中的安全性和有效性：EvolutionRMS1和evolutionRMS2是两项多中心、随机、双盲、双假、活性对照的3期试验，在52个国家的701个多发性硬化症中心和神经病学诊所进行。研究对象包括 18-55 岁的复发性多发性硬化症成人患者（扩展残疾状态量表 [EDSS] 评分为 0-0-5-5）。参与者通过中央交互式网络响应系统被随机分配（1:1）到埃沃布鲁替尼（45 毫克，每天两次，安慰剂每天一次）或特利福罗米（14 毫克，每天一次，安慰剂每天两次）治疗方案中，所有药物均在非禁食状态下口服，并按地理区域和基线 EDSS 进行分层。所有研究人员和参与者都对研究干预措施进行了蒙蔽。每项研究的主要终点均为年化复发率，以156周内判定的合格复发为基础，采用负二项模型对全部分析集（定义为所有随机分配的参与者）进行评估。这些研究已在 ClinicalTrials.gov 注册（evolutionRMS1 为 NCT04338022，evolutionRMS2 为 NCT04338061，两项研究均已终止）：主要分析使用了从 2020 年 6 月 12 日至 2023 年 10 月 2 日收集的 2290 名随机分配参与者的数据。1124名参与者被纳入evolutionRMS1的完整分析集（evobrutinib组560人，特立氟胺组564人），1166名参与者被纳入evolutionRMS2的完整分析集（每组583人）。evolutionRMS1组有751人（66-8%）为女性，373人（33-1%）为男性；evolutionRMS2组有783人（67-2%）为女性，383人（32-8%）为男性。evobrutinib的年复发率为0-15（95% CI 0-12-0-18 vs 0-14 [0-11-0-18] teriflunomide（调整后RR 1-02 [0-75-1-39]; p=0-55），evolutionRMS1的年复发率为0-11（0-09-0-13 vs 0-11 [0-09-0-13]; 调整后RR 1-00 [0-74-1-35]; p=0-51），evolutionRMS2的年复发率为0-11（0-09-0-13 vs 0-11 [0-09-0-13]; 调整后RR 1-00 [0-74-1-35]; p=0-51）。各治疗组中出现任何治疗突发不良事件（TEAE）的总人数比例相似（埃沃布替尼治疗组1140人中有976人[85-6%]，特立氟胺治疗组1146人中有999人[87-2%]）。最常报告的TEAE为COVID-19（埃沃布替尼223 [19-6%] vs 特立氟胺223 [19-5%]）、丙氨酸氨基转移酶升高（173 [15-2%] vs 204 [17-8%]）、天冬氨酸氨基转移酶升高（110 [9-6%] vs 131 [11-4%]）和头痛（175 [15-4%] vs 176 [15-4%]）。evobrutinib的严重TEAE发生率高于特立氟胺（86 [7-5%] vs 64 [5-6%]）。evobrutinib的肝酶升高至少为正常值上限的5倍，比特立氟胺更常见，尤其是在前12周（55 [5-0%] vs 9 [解释：evobrutinib的疗效比特立氟胺好，但肝酶升高至少为正常值上限的5倍：evobrutinib的疗效并不优于特立氟胺。总之，疗效和肝脏相关安全性研究结果均不支持在复发性多发性硬化症患者中使用evobrutinib：默克公司。
{"title":"Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials.","authors":"Xavier Montalban, Patrick Vermersch, Douglas L Arnold, Amit Bar-Or, Bruce A C Cree, Anne H Cross, Eva Kubala Havrdova, Ludwig Kappos, Olaf Stuve, Heinz Wiendl, Jerry S Wolinsky, Frank Dahlke, Claire Le Bolay, Li Shen Loo, Sathej Gopalakrishnan, Yann Hyvert, Andrija Javor, Hans Guehring, Nadia Tenenbaum, Davorka Tomic","doi":"10.1016/S1474-4422(24)00328-4","DOIUrl":"10.1016/S1474-4422(24)00328-4","url":null,"abstract":"<p><strong>Background: </strong>Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis.</p><p><strong>Methods: </strong>EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated).</p><p><strong>Findings: </strong>The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1119-1132"},"PeriodicalIF":45.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-10DOI: 10.1016/S1474-4422(24)00314-4
Jules Morgan
{"title":"Learning to be an adult with a disability.","authors":"Jules Morgan","doi":"10.1016/S1474-4422(24)00314-4","DOIUrl":"10.1016/S1474-4422(24)00314-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1086"},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1016/S1474-4422(24)00353-3
Steve Vucic
{"title":"Trial designs for motor neuron disease in the 21st century.","authors":"Steve Vucic","doi":"10.1016/S1474-4422(24)00353-3","DOIUrl":"10.1016/S1474-4422(24)00353-3","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1065-1066"},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-18DOI: 10.1016/S1474-4422(24)00376-4
Arjune Sen, Neerja Chowdhary, Asma Hallab, Michele Romoli, J Helen Cross, Bernadette Cappello
{"title":"Equitable access to levetiracetam for people with epilepsy.","authors":"Arjune Sen, Neerja Chowdhary, Asma Hallab, Michele Romoli, J Helen Cross, Bernadette Cappello","doi":"10.1016/S1474-4422(24)00376-4","DOIUrl":"10.1016/S1474-4422(24)00376-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"1076-1077"},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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