John H Stone, Arezou Khosroshahi, Wen Zhang, Emanuel Della Torre, Kazuichi Okazaki, Yoshiya Tanaka, J Matthias Löhr, Nicolas Schleinitz, Lingli Dong, Hisanori Umehara, Marco Lanzillotta, Zachary S Wallace, Mikael Ebbo, George J Webster, Fernando Martinez Valle, Manu K Nayar, Cory A Perugino, Vinciane Rebours, Xinxin Dong, Yanping Wu, Qing Li, Nishi Rampal, Daniel Cimbora, Emma L Culver
Background: IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease.
Methods: In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission.
Results: A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo.
Conclusions: Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).
背景IgG4相关疾病是一种多器官、复发性、纤维炎症性、免疫介导的疾病，目前尚无获批疗法。伊奈珠单抗能靶向消耗 CD19+ B 细胞，可能对治疗 IgG4 相关疾病患者有效：在这项3期、多中心、双盲、随机、安慰剂对照试验中，患有活动性IgG4相关疾病的成人按1:1的比例随机接受伊奈珠单抗（第1天、第15天和第26周静脉注射300毫克）或安慰剂，治疗期为52周。两组患者均接受相同的糖皮质激素减量治疗。允许使用糖皮质激素治疗疾病复发，但不允许使用背景免疫抑制剂。主要终点是在治疗期间首次出现经治疗和判定的疾病复发，以时间到事件分析法进行评估。主要次要终点是年复发率以及无治疗和无糖皮质激素完全缓解率：共有135名IgG4相关疾病患者接受了随机分配：68名参与者被分配接受伊维单抗治疗，67名参与者被分配接受安慰剂治疗。伊维单抗治疗降低了复发风险；伊维单抗组有7人（10%）至少复发一次，而安慰剂组有40人（60%）复发（危险比为0.13；95%置信区间[CI]为0.06至0.28；PConclusions.）：伊尼单抗降低了IgG4相关疾病复发的风险，并增加了1年后无复发完全缓解的可能性，证实了CD19靶向B细胞清除作为IgG4相关疾病潜在治疗方法的作用。(由安进公司资助；MITIGATE ClinicalTrials.gov 编号：NCT04540497）。
{"title":"Inebilizumab for Treatment of IgG4-Related Disease.","authors":"John H Stone, Arezou Khosroshahi, Wen Zhang, Emanuel Della Torre, Kazuichi Okazaki, Yoshiya Tanaka, J Matthias Löhr, Nicolas Schleinitz, Lingli Dong, Hisanori Umehara, Marco Lanzillotta, Zachary S Wallace, Mikael Ebbo, George J Webster, Fernando Martinez Valle, Manu K Nayar, Cory A Perugino, Vinciane Rebours, Xinxin Dong, Yanping Wu, Qing Li, Nishi Rampal, Daniel Cimbora, Emma L Culver","doi":"10.1056/NEJMoa2409712","DOIUrl":"https://doi.org/10.1056/NEJMoa2409712","url":null,"abstract":"<p><strong>Background: </strong>IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease.</p><p><strong>Methods: </strong>In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission.</p><p><strong>Results: </strong>A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo.</p><p><strong>Conclusions: </strong>Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632649","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":"Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages.","authors":"Qian Wang, Yicheng Guo, Jerren Ho, David D Ho","doi":"10.1056/NEJMc2410203","DOIUrl":"https://doi.org/10.1056/NEJMc2410203","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 19","pages":"1863-1864"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632655","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":"Immunobridging for Pemivibart, a Monoclonal Antibody for Prevention of Covid-19.","authors":"Pete Schmidt, Yong Li, Myra Popejoy","doi":"10.1056/NEJMc2404555","DOIUrl":"https://doi.org/10.1056/NEJMc2404555","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 19","pages":"1860-1862"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632669","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":"Transcatheter Repair or Surgery for Functional Mitral Regurgitation.","authors":"Joanna Chikwe, Michelle M Kittleson","doi":"10.1056/NEJMe2411217","DOIUrl":"https://doi.org/10.1056/NEJMe2411217","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 19","pages":"1850-1851"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632686","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 : 2024-11-14Epub Date: 2024-10-30DOI: 10.1056/NEJMp2413125
Madeline R Sterling, David C Grabowski
{"title":"Covering Long-Term Care at Home? Implications of a New Proposal for Expanding Medicare.","authors":"Madeline R Sterling, David C Grabowski","doi":"10.1056/NEJMp2413125","DOIUrl":"10.1056/NEJMp2413125","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"e41"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548968","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 : 2024-11-14Epub Date: 2024-09-15DOI: 10.1056/NEJMe2411490
Eric J Rubin, Oladapo O Yeku, Stephen Morrissey
{"title":"NEJM at ESMO - Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.","authors":"Eric J Rubin, Oladapo O Yeku, Stephen Morrissey","doi":"10.1056/NEJMe2411490","DOIUrl":"10.1056/NEJMe2411490","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"e44"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301184","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 : 2024-11-14Epub Date: 2024-08-31DOI: 10.1056/NEJMe2410898
Eric J Rubin, Jane Leopold, Stephen Morrissey
{"title":"NEJM at ESC - Transcatheter Repair versus Surgery for Secondary Mitral Regurgitation.","authors":"Eric J Rubin, Jane Leopold, Stephen Morrissey","doi":"10.1056/NEJMe2410898","DOIUrl":"10.1056/NEJMe2410898","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"e45"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121198","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 : 2024-11-14Epub Date: 2024-08-31DOI: 10.1056/NEJMe2410896
Eric J Rubin, Jane Leopold, Stephen Morrissey
{"title":"NEJM at ESC - Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.","authors":"Eric J Rubin, Jane Leopold, Stephen Morrissey","doi":"10.1056/NEJMe2410896","DOIUrl":"10.1056/NEJMe2410896","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"e46"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121199","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":"Integrating Community Health Workers in Rhode Island - A Roadmap toward Health Equity.","authors":"Somava Saha, Geraldine McPhee, Swanette Salazar, Deborah Garneau","doi":"10.1056/NEJMp2409034","DOIUrl":"https://doi.org/10.1056/NEJMp2409034","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 19","pages":"1768-1769"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632671","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":"Toward Curing More Patients with Bladder Cancer - A New Perioperative Strategy.","authors":"Matthew I Milowsky","doi":"10.1056/NEJMe2411608","DOIUrl":"https://doi.org/10.1056/NEJMe2411608","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 19","pages":"1848-1849"},"PeriodicalIF":96.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632683","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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