New England Journal of Medicine最新文献

{"title":"Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis.","authors":"Robert J Fox, Amit Bar-Or, Anthony Traboulsee, Celia Oreja-Guevara, Gavin Giovannoni, Patrick Vermersch, Sana Syed, Ye Li, Wendy S Vargas, Timothy J Turner, Erik Wallstroem, Daniel S Reich","doi":"10.1056/NEJMoa2415988","DOIUrl":"10.1056/NEJMoa2415988","url":null,"abstract":"<p><strong>Background: </strong>Throughout the course of multiple sclerosis, gradually progressive neurologic impairment can occur, which has been called disability accrual. Current disease-modifying therapies for multiple sclerosis have limited effects on disability accrual unrelated to relapses, which is thought to be partially caused by chronic, nonresolving neuroinflammation within the central nervous system. Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B cells in both the periphery and central nervous system. There are no approved treatments for nonrelapsing secondary progressive multiple sclerosis.</p><p><strong>Methods: </strong>In a phase 3, double-blind, placebo-controlled, event-driven trial, we randomly assigned participants with nonrelapsing secondary progressive multiple sclerosis, in a 2:1 ratio, to receive tolebrutinib (60 mg once daily) or matching placebo. The primary end point was confirmed disability progression that was sustained for at least 6 months, assessed in a time-to-event analysis.</p><p><strong>Results: </strong>A total of 1131 participants underwent randomization: 754 were assigned to receive tolebrutinib and 377 to receive placebo. The median follow-up was 133 weeks. A smaller percentage of participants in the tolebrutinib group than in the placebo group had confirmed disability progression sustained for at least 6 months (22.6% vs. 30.7%; hazard ratio, 0.69; 95% confidence interval, 0.55 to 0.88; P = 0.003). Serious adverse events occurred in 15.0% of the participants in the tolebrutinib group and in 10.4% of those in the placebo group. A total of 4.0% of the participants in the tolebrutinib group and 1.6% of those in the placebo group had increases in alanine aminotransferase levels to more than 3 times the upper limit of the normal range.</p><p><strong>Conclusions: </strong>In participants with nonrelapsing secondary progressive multiple sclerosis, the risk of disability progression was lower among those who received treatment with tolebrutinib than among those who received placebo. (Funded by Sanofi; HERCULES ClinicalTrials.gov number, NCT04411641.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1883-1892"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812905","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}

{"title":"Alternative Complement Pathway, Iptacopan, and IgA Nephropathy.","authors":"Andrea Angeletti, Maddalena Marasa, Paolo Cravedi","doi":"10.1056/NEJMc2503117","DOIUrl":"https://doi.org/10.1056/NEJMc2503117","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 19","pages":"1976"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081707","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}

{"title":"Case 14-2025: A 29-Year-Old Woman with Peritonsillar Swelling and Bleeding.","authors":"Rahmatullah Wais Rahmati,Katherine L Reinshagen,Rosh K V Sethi,David S Shulman,Emily M Hartsough","doi":"10.1056/nejmcpc2300972","DOIUrl":"https://doi.org/10.1056/nejmcpc2300972","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"40 1","pages":"1954-1964"},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982479","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}

{"title":"Targeting Orexin Receptors to Treat Narcolepsy.","authors":"Clifford B Saper","doi":"10.1056/nejme2502806","DOIUrl":"https://doi.org/10.1056/nejme2502806","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"14 1","pages":"1968-1971"},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982480","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}

{"title":"Progress in the Development of N-of-1 Therapy.","authors":"Peter Marks","doi":"10.1056/nejme2505704","DOIUrl":"https://doi.org/10.1056/nejme2505704","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"232 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065714","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}

{"title":"Plight on the Pickleball Court.","authors":"Catherina X Pan, Anand Vaidya, Daniel P Marcusa, Jacob A Burns, Thomas Michel","doi":"10.1056/NEJMimc2404464","DOIUrl":"https://doi.org/10.1056/NEJMimc2404464","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 19","pages":"e46"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081714","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}

{"title":"Alternative Complement Pathway, Iptacopan, and IgA Nephropathy.","authors":"Felix Poppelaars,Bernardo Faria,Joshua M Thurman","doi":"10.1056/nejmc2503117","DOIUrl":"https://doi.org/10.1056/nejmc2503117","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"77 1","pages":"1975"},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982475","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}

{"title":"Alternative Complement Pathway, Iptacopan, and IgA Nephropathy. Reply.","authors":"Jonathan Barratt, Vlado Perkovic, Dana V Rizk","doi":"10.1056/NEJMc2503117","DOIUrl":"https://doi.org/10.1056/NEJMc2503117","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 19","pages":"1976"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081708","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}

{"title":"Hair Tourniquet.","authors":"Anton Ivan Moorees, Dirk Vervloessem","doi":"10.1056/NEJMicm2416174","DOIUrl":"https://doi.org/10.1056/NEJMicm2416174","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 19","pages":"e44"},"PeriodicalIF":96.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081712","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}

{"title":"Personalized Gene Editing to Treat an Inborn Error of Metabolism.","authors":"Andrea L Gropman,Alexis C Komor","doi":"10.1056/nejme2505721","DOIUrl":"https://doi.org/10.1056/nejme2505721","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"124 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065713","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}