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
{"title":"阿仑单抗13岁以上的安全性和有效性 复发-缓解型多发性硬化症的年数：开放标签TOPAZ研究的最终结果。","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":null,"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":4,"journal":{"name":"ACS Applied Energy Materials","volume":null,"pages":null},"PeriodicalIF":5.4000,"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":"0","resultStr":"{\"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\":null,\"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. 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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\":4,\"journal\":{\"name\":\"ACS Applied Energy Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.4000,\"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\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Energy Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562864231194823\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Energy Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864231194823","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study.
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.
期刊介绍：
ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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